Relationship between surgical difficulty and postoperative complications of hand-assisted laparoscopic living donor nephrectomy and establishment of prediction model.

BACKGROUND: Few studies have systematically explored the factors influencing the difficulty of hand-assisted laparoscopic living donor nephrectomy. To investigate the relationship between the difficulty of hand-assisted laparoscopic living donor nephrectomy and postoperative complications of the donor as well as the recipient, and then build a model for predicting the difficulty of surgery. METHODS: In this study, 60 patients who underwent hand-assisted laparoscopic living donor nephrectomy by the same surgeon from September 2022 to March 2024 were included as the modeling group. 20 patients operated on by another surgeon served as the external validation group. The subjective score (1-3 points) of surgical difficulty was used as the quantitative index of surgical difficulty. Pearson and Spearman correlation tests were used to explore the correlation between preoperative data and surgical difficulty scores of kidney donors, and finally built a prediction model through multiple linear regression analysis. RESULTS: With the increase in the difficulty of operation, both donors and recipients' complications were increased. Linear regression analysis showed that only the number of renal arteries, visceral fat thickness and MAP score were independent risk factors for the difficulty of hand-assisted laparoscopic living donor nephrectomy. The prediction equation is as follows: Difficulty score = 0.584*Number of renal arteries + 0.731*MAP score + 0.110*visceral fat thickness. CONCLUSIONS: Donors with higher surgical difficulty are more likely to have serious complications after surgery as well as the recipient. We also established a reliable prediction model for the difficulty of hand-assisted laparoscopic donor nephrectomy.

Relationship between hearing loss and depression: A cross-sectional analysis from the National Health and Nutrition Examination Survey 2015-2018.

BACKGROUND: Hearing loss is a prevalent issue resulting from loud noise exposure, aging, diseases, and genetic differences. As individuals age, the likelihood of experiencing hearing loss and depression escalates; yet, the link between hearing loss and the risk of depression remains ambiguous. This study explores the relationship between hearing and depression risk, taking into account sociodemographic and health-related factors. METHODS: Using data from the National Health and Nutrition Examination Survey (NHANES) 2015-2018, a cross-sectional analysis was conducted, focusing on adult participants. It evaluated their hearing status and depression levels using the Patient Health Questionnaire-9 (PHQ-9). The study examined a range of variables, such as age, gender, socioeconomic status, lifestyle choices, and comorbidities, to understand their influence on the link between hearing loss and depression. RESULTS: Analysis indicated a significant association between moderate to severe hearing loss and an increased risk of depression, notably in older adults. This relationship remained significant even after adjusting for a variety of sociodemographic and health factors. LIMITATIONS: This is a study using the NHANES database using self-reported surveys. CONCLUSION: The findings of this study emphasize the need to integrate hearing health in the holistic assessment and treatment of depression, particularly advocating for combined care strategies for the elderly.

Serum Branched-Chain Amino Acids and Long-Term Complications of Liver Cirrhosis: Evidence from a Population-Based Prospective Study.

BACKGROUND AND AIMS: The role of serum branched-chain amino acids (BCAAs) in long-term liver cirrhosis complication events remains unclear. We aimed to evaluate the associations between serum BCAAs and the risk of liver-related events. METHODS: We included a total of 64,005 participants without liver cirrhosis complication events at baseline from the UK Biobank. Cox proportional hazards regression models were utilized to estimate multivariable hazard ratios (HRs) and 95% CIs for the incidence of liver cirrhosis complication events, adjusting for potential confounders, including sociodemographic and lifestyle factors. Relationships between serum BCAAs and liver cirrhosis complications were examined using nonparametrically restricted cubic spline regression. RESULTS: During a median follow-up of 12.7 years, 583 participants developed liver cirrhosis complication events. The multivariable Cox regression model suggested that total BCAAs (HR = 0.88, 95% CI 0.82-0.95), serum leucine (HR = 0.88, 95% CI 0.81-0.95), serum isoleucine (HR = 0.88, 95% CI 0.82-0.96), and serum valine (HR = 0.87, 95% CI 0.82-0.96) were all independent protective factors for liver cirrhosis complications after adjustment for sociodemographic and lifestyle factors. Cox models with restricted cubic splines showed U-shaped associations between serum valine and liver cirrhosis complication incidence. Serum total BCAA and isoleucine concentrations might reduce the risk of liver cirrhosis complications by raising the risk of (type 2 diabetes mellitus) T2DM. CONCLUSION: Lower serum BCAA levels exacerbate the long-term risk of liver cirrhosis complications. Future studies should confirm these findings and identify the biological pathways of these associations.

Modulation of Comorbid Chronic Neuropathic Pain and Anxiety-Like Behaviors by Glutamatergic Neurons in the vlPAG and the Analgesic and Anxiolytic Effects of EA.

Comorbid chronic neuropathic pain and anxiety is a common disease that represents a major clinical challenge. The underlying mechanisms of chronic neuropathic pain and anxiety are not entirely understood, which limits the exploration of effective treatment methods. Glutamatergic neurons in the ventrolateral periaqueductal gray (vlPAG) have been implicated in regulating pain, but the potential roles of the vlPAG in neuropathic pain-induced anxiety have not been investigated. Herein, whole-cell recording and immunofluorescence showed that the excitability of CamkIIα neurons in the vlPAG (vlPAGCamkIIα+ neurons) was decreased in mice with spared nerve injury (SNI), while electroacupuncture (EA) activated these neurons. We also showed that chemogenetic inhibition of vlPAGCamkIIα+ neurons resulted in allodynia and anxiety-like behaviors in naive mice. Furthermore, chemogenetic activation of vlPAGCamkIIα+ neurons reduced anxiety-like behaviors and allodynia in mice with SNI, and EA had a similar effect in alleviating these symptoms. Nevertheless, EA combined with chemogenetic activation failed to further relieve allodynia and anxiety-like behaviors. Artificial inhibition of vlPAGCamkIIα+ neurons abolished the analgesic and anxiolytic effects of EA. Overall, our study reveals a novel mechanism of neuropathic pain-induced anxiety and shows that EA may relieve comorbid chronic neuropathic pain and anxiety by activating vlPAGCamkIIα+ neurons.Significance Statement Neuropathic pain is clinically accompanied by anxiety. Both glutamatergic neurons in the ventrolateral periaqueductal gray (vlPAG) and electroacupuncture (EA) have demonstrated analgesic properties. However, the efficacy of these interventions in addressing neuropathic pain and its concomitant anxiety has yet to be fully elucidated. In a mice model of spared nerve injury (SNI), we observed a decreased excitability of vlPAG CamkIIα neurons. Remarkably, EA treatment significantly enhanced the excitability of these neurons. Further, chemogenetic activation of vlPAGCamkIIα+ neurons not only resulted in analgesia but also mitigated anxiety-like behaviors in SNI mice, mirroring the effects observed with EA treatment. Conversely, inhibition of vlPAGCamkIIα+ neurons activity in naive mice reduced pain thresholds and induced anxiety-like behavior, while also negating the beneficial effects of EA. These findings provide novel insights into the mechanistic interplay between chronic neuropathic pain and anxiety, highlighting the therapeutic potential of targeting vlPAG glutamatergic neurons in these conditions.

Generation of allogeneic CAR-NKT cells from hematopoietic stem and progenitor cells using a clinically guided culture method.

Cancer immunotherapy with autologous chimeric antigen receptor (CAR) T cells faces challenges in manufacturing and patient selection that could be avoided by using 'off-the-shelf' products, such as allogeneic CAR natural killer T (AlloCAR-NKT) cells. Previously, we reported a system for differentiating human hematopoietic stem and progenitor cells into AlloCAR-NKT cells, but the use of three-dimensional culture and xenogeneic feeders precluded its clinical application. Here we describe a clinically guided method to differentiate and expand IL-15-enhanced AlloCAR-NKT cells with high yield and purity. We generated AlloCAR-NKT cells targeting seven cancers and, in a multiple myeloma model, demonstrated their antitumor efficacy, expansion and persistence. The cells also selectively depleted immunosuppressive cells in the tumor microenviroment and antagonized tumor immune evasion via triple targeting of CAR, TCR and NK receptors. They exhibited a stable hypoimmunogenic phenotype associated with epigenetic and signaling regulation and did not induce detectable graft versus host disease or cytokine release syndrome. These properties of AlloCAR-NKT cells support their potential for clinical translation.

Engineering allorejection-resistant CAR-NKT cells from hematopoietic stem cells for off-the-shelf cancer immunotherapy.

The clinical potential of current FDA-approved chimeric antigen receptor (CAR)-engineered T (CAR-T) cell therapy is encumbered by its autologous nature, which presents notable challenges related to manufacturing complexities, heightened costs, and limitations in patient selection. Therefore, there is a growing demand for off-the-shelf universal cell therapies. In this study, we have generated universal CAR-engineered NKT (UCAR-NKT) cells by integrating iNKT TCR engineering and HLA gene editing on hematopoietic stem cells (HSCs), along with an ex vivo, feeder-free HSC differentiation culture. The UCAR-NKT cells are produced with high yield, purity, and robustness, and they display a stable HLA-ablated phenotype that enables resistance to host cell-mediated allorejection. These UCAR-NKT cells exhibit potent antitumor efficacy to blood cancers and solid tumors, both in vitro and in vivo, employing a multifaceted array of tumor-targeting mechanisms. These cells are further capable of altering the tumor microenvironment by selectively depleting immunosuppressive tumor-associated macrophages and myeloid-derived suppressor cells. In addition, UCAR-NKT cells demonstrate a favorable safety profile with low risks of graft-versus-host disease and cytokine release syndrome. Collectively, these preclinical studies underscore the feasibility and significant therapeutic potential of UCAR-NKT cell products and lay a foundation for their translational and clinical development.

Development of a Risk Prediction Model for Infection After Kidney Transplantation Transmitted from Bacterial Contaminated Preservation Solution.

Background: The risk of transplant recipient infection is unknown when the preservation solution culture is positive. Methods: We developed a prediction model to evaluate the infection in kidney transplant recipients within microbial contaminated preservation solution. Univariate logistic regression was utilized to identify risk factors for infection. Both stepwise selection with Akaike information criterion (AIC) was used to identify variables for multivariate logistic regression. Selected variables were incorporated in the nomograms to predict the probability of infection for kidney transplant recipients with microbial contaminated preservation solution. Results: Age, preoperative creatinine, ESKAPE, PCT, hemofiltration, and sirolimus had a strongest association with infection risk, and a nomogram was established with an AUC value of 0.72 (95% confidence interval, 0.64-0.80) and Brier index 0.20 (95% confidence interval, 0.18-0.23). Finally, we found that when the infection probability was between 20% and 80%, the model oriented antibiotic strategy should have higher net benefits than the default strategy using decision curve analysis. Conclusion: Our study developed and validated a risk prediction model for evaluating the infection of microbial contaminated preservation solutions in kidney transplant recipients and demonstrated good net benefits when the total infection probability was between 20% and 80%.

Comparison between Retroperitoneal Laparoscopic Nephrectomy and Traditional Open Nephrectomy to Treat Polycystic Kidney Disease before Kidney Transplantation.

PURPOSE: To compare the efficiency and safety between retroperitoneal laparoscopic nephrectomy and traditional open nephrectomy to treat autosomal-dominant polycystic kidney disease before kidney transplantation. MATERIALS AND METHODS: A total of 57 patients diagnosed with huge autosomal-dominant polycystic kidney disease between 2000 and 2020 at our center were included in this study. Patients were divided into a retroperitoneal laparoscopic (RL; n=23) group and traditional open (TO; n = 34) group. We retrospectively analyzed and compared preoperative and perioperative variables between the two groups. RESULTS: Patients in the RL group showed a longer operation time (201.09±83.76min) compared to patients in the TO group (113.38 ± 51.84min, p < 0.001). The RL group also showed significantly less intraoperative blood loss (p = 0.025) and less intraoperative blood transfusion volume (p = 0.016) compared to the TO group. Meanwhile, time of gastrointestinal function recovery, bed leave, catheter indwelling and postoperative hospitalization in the RL group were 2.13 ± 0.63, 1.30 ± 1.0, 5.22 ± 2.09, 7.35±2.48 days, respectively, which were significantly shorter than the TO group (p < 0.05). Pain degree of patients during the first 48 hours after operation was similar between the RL and TO groups, but the opioid use percentage in the RL group was 8.70% (2/23) and was lower than the 26.47% (9/34) in the TO group (p = 0.022). Meanwhile, 5 and 23 patients exhibited postoperative complications in the RL and TO groups, respectively (p < 0.001). CONCLUSION: Both retroperitoneal laparoscopic nephrectomy and traditional open surgery are feasible to treat huge polycystic nephrectomy. However, patients who undergo retroperitoneal laparoscopic nephrectomy experience higher levels of safety and recover more rapidly.

Music intervention in patients undergoing hematopoietic stem cell transplantation: A systematic review and meta-analysis.

AIMS: To explore whether music intervention improves the quality of life (QOL) of patients undergoing hematopoietic stem cell transplantation (HSCT) and to evaluate its impact on patients' symptoms of depression/anxiety and fatigue. METHODS: This systematic review and meta-analysis was conducted in accordance with the Preferred Reporting Items of Systematic reviews and Meta-Analyses (PRISMA) guidelines. The databases PubMed, Cochrane CENTRAL, and EMBASE were searched from inception to September 30, 2022. The search strategy used a combination of the keywords "music" and "hematopoietic stem cell transplantation" or "HSCT." The outcomes assessed were QOL, depression and anxiety, and fatigue. Pooled standardized mean differences with 95% confidence intervals were calculated to compare the outcomes between the music intervention and control groups. Heterogeneity across the studies was assessed using a chi-square-based test, and the I2 and Q statistics. RESULTS: Meta-analysis of the included study population showed that music intervention for patients undergoing HSCT was associated with patients' improved QOL, and resulted in reduced depression/anxiety and fatigue compared to patients without music intervention. CONCLUSION: Music intervention benefits HSCT outcomes, including better QOL, less depression/anxiety, and less fatigue postoperatively. Future trials with larger samples are still warranted to strengthen the evidence supporting the benefits of music intervention in this patient population.

miR-377-3p Regulates Hippocampal Neurogenesis via the Zfp462-Pbx1 Pathway and Mediates Anxiety-Like Behaviors in Prenatal Hypoxic Offspring.

Prenatal hypoxia (PH) is one of the most common complications of obstetrics and is closely associated with many neurological disorders such as depression, anxiety, and cognitive impairment. Our previous study found that Zfp462 heterozygous (Het) mice exhibit significant anxiety-like behavior. Interestingly, offspring mice with PH also have anxiety-like behaviors in adulthood, accompanied by reduced expression of Zfp462 and increased expression of miR-377-3p; however, the exact regulatory mechanisms remain unclear. In this study, western blotting, gene knockdown, immunofluorescence, dual-luciferase reporter assay, immunoprecipitation, cell transfection with miR-377-3p mimics or inhibitors, quantitative real-time PCR, and rescue assay were used to detect changes in the miR-377-3p-Zfp462-Pbx1 (pre-B-cell leukemia homeobox1) pathway in the brains of prenatal hypoxic offspring to explain the pathogenesis of anxiety-like behaviors. We found that Zfp462 deficiency promoted Pbx1 protein degradation through ubiquitination and that Zfp462 Het mice showed downregulation of the protein kinase B (PKB, also called Akt)-glycogen synthase kinase-3ß (GSK3ß)-cAMP response element-binding protein (CREB) pathway and hippocampal neurogenesis with anxiety-like behavior. In addition, PH mice exhibited upregulation of miR-377-3p, downregulation of Zfp462/Pbx1-Akt-GSK3ß-CREB pathway activity, reduced hippocampal neurogenesis, and an anxiety-like phenotype. Intriguingly, miR-377-3p directly targets the 3'UTR of Zfp462 mRNA to regulate Zfp462 expression. Importantly, microinjection of miR-377-3p antagomir into the hippocampal dentate gyrus of PH mice upregulated Zfp462/Pbx1-Akt-GSK3ß-CREB pathway activity, increased hippocampal neurogenesis, and improved anxiety-like behaviors. Collectively, our findings demonstrated a crucial role for miR-377-3p in the regulation of hippocampal neurogenesis and anxiety-like behaviors via the Zfp462/Pbx1-Akt-GSK3ß-CREB pathway. Therefore, miR-377-3p could be a potential therapeutic target for anxiety-like behavior in prenatal hypoxic offspring.

A neural circuit associated with anxiety-like behaviors induced by chronic inflammatory pain and the anxiolytic effects of electroacupuncture.

AIMS: Negative emotions induced by chronic pain are a serious clinical problem. Electroacupuncture (EA) is a clinically proven safe and effective method to manage pain-related negative emotions. However, the circuit mechanisms underlying the effect of EA treatment on negative emotions remain unclear. METHODS: Plantar injection of complete Freund's adjuvant (CFA) was performed to establish a rat model of chronic inflammatory pain-induced anxiety-like behaviors. Adeno-associated virus (AAV) tracing was used to identify excitatory synaptic transmission from the rostral anterior cingulate cortex (rACC) to the dorsal raphe nucleus (DRN). Employing chemogenetic approaches, we examined the role of the rACC-DRN circuit in chronic pain-induced anxiety-like behaviors and investigated whether EA could reverse chronic pain-induced dysfunctions of the rACC-DRN circuit and anxiety-like behaviors. RESULTS: We found that chemogenetic activation of the rACC-DRN circuit alleviated CFA-induced anxiety-like behaviors, while chemogenetic inhibition of the rACC-DRN circuit resulted in short-term CFA-induced anxiety-like behaviors. Further research revealed that the development of CFA-induced anxiety-like behaviors was attributed to the dysfunction of rACC CaMKII neurons projecting to DRN serotonergic neurons (rACCCaMKII-DRN5-HT neurons) but not rACC CaMKII neurons projecting to DRN GABAergic neurons (rACCCaMKII-DRNGABA neurons). This is supported by the findings that chemogenetic activation of the rACCCaMKII-DRN5-HT circuit alleviates anxiety-like behaviors in rats with chronic pain, whereas neither chemogenetic inhibition nor chemogenetic activation of the rACCCaMKII-DRNGABA circuit altered CFA chronic pain-evoked anxiety-like behaviors in rats. More importantly, we found that EA could reverse chronic pain-induced changes in the activity of rACC CaMKII neurons and DRN 5-HTergic neurons and that chemogenetic inhibition of the rACCCaMKII-DRN5-HT circuit blocked the therapeutic effects of EA on chronic pain-induced anxiety-like behaviors. CONCLUSIONS: Our data suggest that the reversal of rACCCaMKII-DRN5-HT circuit dysfunction may be a mechanism underlying the therapeutic effect of EA on chronic pain-induced anxiety-like behaviors.

Profiling ovarian cancer tumor and microenvironment during disease progression for cell-based immunotherapy design.

Ovarian cancer (OC) is highly lethal due to late detection and frequent recurrence. Initial treatments, comprising surgery and chemotherapy, lead to disease remission but are invariably associated with subsequent relapse. The identification of novel therapies and an improved understanding of the molecular and cellular characteristics of OC are urgently needed. Here, we conducted a comprehensive analysis of primary tumor cells and their microenvironment from 16 chemonaive and 10 recurrent OC patient samples. Profiling OC tumor biomarkers allowed for the identification of potential molecular targets for developing immunotherapies, while profiling the microenvironment yielded insights into its cellular composition and property changes between chemonaive and recurrent samples. Notably, we identified CD1d as a biomarker of the OC microenvironment and demonstrated its targeting by invariant natural killer T (iNKT) cells. Overall, our study presents a comprehensive immuno-profiling of OC tumor and microenvironment during disease progression, guiding the development of immunotherapies for OC treatment, especially for recurrent disease.

Analysis of Anxiety and Influencing Factors in Kidney Transplant Recipients and General Public During the COVID-19 Pandemic.

BACKGROUND The COVID-19 pandemic has had a profound impact on mental health worldwide. Kidney transplant recipients represent a vulnerable population that may experience increased anxiety due to their health concerns and the risk of infection. This study aims to delve into the psychological anxiety levels and influential factors of kidney transplant patients during the Omicron variant of COVID-19 pandemic in China. MATERIAL AND METHODS A retrospective analysis was conducted using an online survey questionnaire to investigate the anxiety levels of 203 kidney transplant recipients and 53 individuals from the general population. The Self-Rating Anxiety Scale (SAS) was employed to evaluate anxiety levels, and the influencing factors affecting anxiety levels were analyzed for both cohorts. RESULTS Among the cohort of the 203 kidney transplant recipients, 28 individuals (13.8%) had symptoms indicative of anxiety, with an average SAS score of 40.5±9.0. Out of the 53 individuals from the general population, 9 (17.0%) had symptoms of anxiety, with an average SAS score of 39.6±10.7. Notably, females and those with chronic respiratory diseases within the general population showed higher anxiety levels, and having a chronic respiratory condition was found to be an independent risk factor for anxiety levels in the general population. CONCLUSIONS This investigation demonstrates that anxiety levels in kidney transplant recipients and the general population were comparable during the Omicron variant of COVID-19 pandemic. However, kidney transplant patients showed more stable anxiety levels.

Advancements in CRISPR screens for the development of cancer immunotherapy strategies.

CRISPR screen technology enables systematic and scalable interrogation of gene function by using the CRISPR-Cas9 system to perturb gene expression. In the field of cancer immunotherapy, this technology has empowered the discovery of genes, biomarkers, and pathways that regulate tumor development and progression, immune reactivity, and the effectiveness of immunotherapeutic interventions. By conducting large-scale genetic screens, researchers have successfully identified novel targets to impede tumor growth, enhance anti-tumor immune responses, and surmount immunosuppression within the tumor microenvironment (TME). Here, we present an overview of CRISPR screens conducted in tumor cells for the purpose of identifying novel therapeutic targets. We also explore the application of CRISPR screens in immune cells to propel the advancement of cell-based therapies, encompassing T cells, natural killer cells, dendritic cells, and macrophages. Furthermore, we outline the crucial components necessary for the successful implementation of immune-specific CRISPR screens and explore potential directions for future research.

Exploring the dynamic interplay between cancer stem cells and the tumor microenvironment: implications for novel therapeutic strategies.

Cancer stem cells (CSCs) have emerged as key contributors to tumor initiation, growth, and metastasis. In addition, CSCs play a significant role in inducing immune evasion, thereby compromising the effectiveness of cancer treatments. The reciprocal communication between CSCs and the tumor microenvironment (TME) is observed, with the TME providing a supportive niche for CSC survival and self-renewal, while CSCs, in turn, influence the polarization and persistence of the TME, promoting an immunosuppressive state. Consequently, these interactions hinder the efficacy of current cancer therapies, necessitating the exploration of novel therapeutic approaches to modulate the TME and target CSCs. In this review, we highlight the intricate strategies employed by CSCs to evade immune surveillance and develop resistance to therapies. Furthermore, we examine the dynamic interplay between CSCs and the TME, shedding light on how this interaction impacts cancer progression. Moreover, we provide an overview of advanced therapeutic strategies that specifically target CSCs and the TME, which hold promise for future clinical and translational studies in cancer treatment.

Electroacupuncture alleviates the relapse of pain-related aversive memory by activating KOR and inhibiting GABAergic neurons in the insular cortex.

Pain-related aversive memory is common in chronic pain patients. Electroacupuncture has been demonstrated to block pain-related aversive memory. The insular cortex is a key region closely related to aversive behaviors. In our study, a potential mechanism underlying the effect of electroacupuncture treatment on pain-related aversive memory behaviors relative to the insular cortex was investigated. Our study used the chemogenetic method, pharmacological method, electroacupuncture intervention, and behavioral detection. Our study showed that both inhibition of gamma-aminobutyric acidergic neurons and activation of the kappa opioid receptor in the insular cortex blocked the pain-related aversive memory behaviors induced by 2 crossover injections of carrageenan in mice; conversely, both the activation of gamma-aminobutyric acidergic neurons and inhibition of kappa opioid receptor in the insular cortex play similar roles in inducing pain-related aversive memory behaviors following 2 crossover injections of carrageenan. In addition, activation of gamma-aminobutyric acidergic neurons in the insular cortex reversed the effect of kappa opioid receptor activation in the insular cortex. Moreover, electroacupuncture effectively blocked pain-related aversive memory behaviors in model mice, which was reversed by both activation of gamma-aminobutyric acidergic neurons and inhibition of kappa opioid receptor in the insular cortex. The effect of electroacupuncture on blocking pain-related aversive memory behaviors may be related to the activation of the kappa opioid receptor and inhibition of gamma-aminobutyric acidergic neurons in the insular cortex.

The importance of the thickness of femoral lateral wall for treating intertrochanteric fractures: a finite elements analysis.

To explore how the thickness of the femoral lateral wall influences the effectiveness of internal fixation systems used to treat intertrochanteric fractures. CT images of the pelvis and femur of a male adult were used to construct an intertrochanteric fracture model (AO/OTA 31-A2) with various thicknesses of the femoral lateral wall (FLW). Four finite element (FE) models were created with the lateral femoral walls being 10 mm, 20 mm, 30 mm, and 40 mm thick. The fracture models were fixed with a dynamic hip screw (DHS), a proximal femoral nail anti-rotation (PFNA), and a proximal femoral locking compression plate (P-FLCP). A simulated vertical load was applied to the femoral head. The stress and displacement of the implant and femur in each model were recorded for comparison. The FE analysis of the intertrochanteric fracture models showed that the PFNA system could provide better stability than the DHS and P-FLCP with the same thickness of FLW. The FLW provided buttress support to the femoral head and neck when using a DHS and PFNA, and the buttress strength was proportional to the thickness of FLW. The maximum stress in the DHS model was recorded on the DHS plate which accommodated the lag screw. For the PFNA model, the maximum stress appeared at the connection between the nail and blade. In the P-FLCP model, the maximum stresses were highly concentrated at the connection between the cephalic nails and the proximal plate. The thickness of the femoral lateral wall should be considered an important factor when selecting a suitable internal fixation system for intertrochanteric fractures. Based on the FE analysis, intramedullary fixation, such as PFNA, experiences lower stress levels and a moderate displacement in comparison to DHS and P-FCLP when used to treat intertrochanteric fractures.

Electroacupuncture alleviates mechanical allodynia and anxiety-like behaviors induced by chronic neuropathic pain via regulating rostral anterior cingulate cortex-dorsal raphe nucleus neural circuit.

AIMS: Epidemiological studies in patients with neuropathic pain have demonstrated a strong association between neuropathic pain and psychiatric conditions such as anxiety. Preclinical and clinical work has demonstrated that electroacupuncture (EA) effectively alleviates anxiety-like behaviors induced by chronic neuropathic pain. In this study, a potential neural circuitry underlying the therapeutic action of EA was investigated. METHODS: The effects of EA stimulation on mechanical allodynia and anxiety-like behaviors in animal models of spared nerve injury (SNI) were examined. EA plus chemogenetic manipulation of glutamatergic (Glu) neurons projecting from the rostral anterior cingulate cortex (rACCGlu ) to the dorsal raphe nucleus (DRN) was used to explore the changes of mechanical allodynia and anxiety-like behaviors in SNI mice. RESULTS: Electroacupuncture significantly alleviated both mechanical allodynia and anxiety-like behaviors with increased activities of glutamatergic neurons in the rACC and serotoninergic neurons in the DRN. Chemogenetic activation of the rACCGlu -DRN projections attenuated both mechanical allodynia and anxiety-like behaviors in mice at day 14 after SNI. Chemogenetic inhibition of the rACCGlu -DRN pathway did not induce mechanical allodynia and anxiety-like behaviors under physiological conditions, but inhibiting this pathway produced anxiety-like behaviors in mice at day 7 after SNI; this effect was reversed by EA. EA plus activation of the rACCGlu -DRN circuit did not produce a synergistic effect on mechanical allodynia and anxiety-like behaviors. The analgesic and anxiolytic effects of EA could be blocked by inhibiting the rACCGlu -DRN pathway. CONCLUSIONS: The role of rACCGlu -DRN circuit may be different during the progression of chronic neuropathic pain and these changes may be related to the serotoninergic neurons in the DRN. These findings describe a novel rACCGlu -DRN pathway through which EA exerts analgesic and anxiolytic effects in SNI mice exhibiting anxiety-like behaviors.

Electroacupuncture Inhibits Pain Memory and Related Anxiety-Like Behaviors by Blockading the GABAB Receptor Function in the Midcingulate Cortex.

Pain memory is commonly considered an underlying cause of chronic pain and is also responsible for a range of anxiety. Electroacupuncture (EA) has been shown to ameliorate pain memories and exert anti-anxiety effects. Previous research has indicated that GABAergic neurons and/or GABA receptors (GABARs) in the midcingulate cortex (MCC) have potential associations with chronic pain and anxiety. However, there is no known empirical research that has specifically studied the effects of EA on the GABAergic system in the MCC. Here, we used cross-injection of carrageenan to establish the pain memory rats model. Immunofluorescence were used to detect the excitability of GABAergic neurons within MCC. Von Frey filament, elevated zero maze, and open field tests were used to measure mechanical allodynia and anxiety-like behaviors, combined with chemogenetic and pharmacologic technologies. Finally, this study provides evidence that pain memories contribute to generalized negative emotions and that downregulating the activity of GABAergic neurons within MCC could block pain memories and reverse anxiety emotion. Specifically, GABABR is involved in pain memory and related anxiety-like behaviors. Activation of GABAergic neurons in the MCC did not reverse the effects of EA on pain memories and related anxiety-like behaviors, whereas these effects could be reversed by a GABABR agonist. These findings highlight the functional significance of GABABR in the EA-mediated attenuation of pain memories and related anxiety-like behaviors in rats.

A computational analysis of mouse behavior in the sucrose preference test.

The sucrose preference test (SPT) measures the relative preference of sucrose over water to assess hedonic behaviors in rodents. Yet, it remains uncertain to what extent the SPT reflects other behavioral components, such as learning, memory, motivation, and choice. Here, we conducted an experimental and computational decomposition of mouse behavior in the SPT and discovered previously unrecognized behavioral subcomponents associated with changes in sucrose preference. We show that acute and chronic stress have sex-dependent effects on sucrose preference, but anhedonia was observed only in response to chronic stress in male mice. Additionally, reduced sucrose preference induced by optogenetics is not always indicative of anhedonia but can also reflect learning deficits. Even small variations in experimental conditions influence behavior, task outcome and interpretation. Thus, an ostensibly simple behavioral task can entail high levels of complexity, demonstrating the need for careful dissection of behavior into its subcomponents when studying the underlying neurobiology.