Therapeutic Effects of Engineered Exosomes from RAW264.7 Cells Overexpressing hsa-let-7i-5p against Sepsis in Mice-A Comparative Study with Human Placenta-Derived Mesenchymal Stem Cell Exosomes.

This study compared the therapeutic effects of engineered exosomes derived from RAW264.7 cells overexpressing hsa-let-7i-5p (engineered exosomes) to exosomes from human placenta-derived mesenchymal stem cells (hpMSC exosomes) against sepsis-induced acute lung injury. Adult male C57BL/6 mice were divided into lipopolysaccharide (LPS), LPS plus engineered exosome (LEExo), or LPS plus hpMSC exosome (LMExo) groups, alongside control groups. The results showed that lung injury scores (based on pathohistological characteristics) and the levels of lung function alterations, tissue edema, and leukocyte infiltration in LEExo and LMExo groups were comparable and significantly lower than in the LPS group (all p < 0.05). Furthermore, the levels of inflammation (nuclear factor-κB activation, cytokine upregulation), macrophage activation (hypoxia-inducible factor-1α activation, M1 phase polarization), oxidation, and apoptosis were diminished in LEExo and LMExo groups compared to the LPS group (all p < 0.05). Inhibition of hsa-let-7i-5p attenuated the therapeutic effects of both engineered and hpMSC exosomes. These findings underscore the potent therapeutic capacity of engineered exosomes enriched with hsa-let-7i-5p and their potential as an alternative to hpMSC exosomes for sepsis treatment. Continued research into the mechanisms of action and optimization of engineered exosomes could pave the way for their future clinical application.

Parameters of Iliopsoas Plane Immediately Caudal to the Indirect Tendon of Rectus Femoris in Axial Plane Measured on Magnetic Resonance Images in an Adult Eastern Asian Population.

The iliopsoas plane (IP) is a fascial plane deep to the iliopsoas complex and is the target of several novel ultrasound-guided analgesic interventions for hip. Currently, limited information is known about its parameters. From the pelvic magnetic resonance (MR) images of an adult Eastern Asian population (n = 49), the IP width, depth, and needle-beam angle in the axial plane immediately caudal to the level of indirect tendon of rectus femoris (RF) were found to be 10.7 ± 1.6 mm, 48.5 ± 15.5 mm, and 84.2 ± 8.2 degrees, respectively. There was a statistically significant difference in the age categories for IP width, and older patients seemed to have wider IP. Our data may provide applications for the technical modification of ultrasound-guided iliopsoas plane block (IPB) in acute hip pain management and the future development of ultrasound-guided single-needle-entry radiofrequency neuroablation in chronic hip pain management.

Correction to: 4-Phenylbutyric acid protects against vasculitic peripheral neuropathy induced by ischaemia-reperfusion through attenuating endoplasmic reticulum stress.

Unfortunately, Fig. 5 was incorrectly published in the original publication. The complete corrected Fig. 5 is given below.

Optimal measuring timing of cystatin C for early detection of contrast-induced acute kidney injury: A systematic review and meta-analysis.

OBJECTIVE: The optimal measuring timing of serum/plasma Cystatin C (CysC) for early detection of contrast-induced acute kidney injury (CIAKI) remains un-studied. We elucidated further on this issue. METHODS: We searched PubMed, MEDLINE, and Embase from inception until March 2018 for studies evaluating diagnostic accuracy of CysC for detecting CIAKI in patients exposed to contrast agents during diagnostic examinations or cardiac/peripheral catheterizations. RESULTS: A total of 10 relevant studies, comprising 2554 patients, were included and divided into the <24 -h and 24 -h groups based on CysC measuring timing (i.e., hours after contrast agent exposure). Compared with creatinine, pooled diagnostic odds ratio of CysC for detecting CIAKI of the <24 -h and 24 -h groups was 7.59 (95 % confidence interval [CI]: 1.31-44.08) and 53.81 (95 % CI: 13.57-213.26). Pooled sensitivity of the <24 -h and 24 -h groups was 0.81 and 0.88. Pooled specificity of the <24 -h and 24 -h groups was 0.64 and 0.88, respectively. Area under the hierarchical summary receiver operating characteristic curve of the <24 -h and 24 -h groups was 0.75 and 0.93. CONCLUSIONS: Measuring CysC at 24 h after contrast agent exposure shows higher diagnostic accuracy for early detection of CIAKI than measuring CysC at <24 h after contrast agent exposure.

Diagnosis and interventional pain management options for sacroiliac joint pain.

The sacroiliac (SI) joint is among the most common sources of chronic low back pain, accounting for 15%-30% of patients presenting chronic low back pain. The complex anatomic structures, nerve innervation, and functional biomechanisms of the SI region make it challenging to diagnose and treat the SI joint as a pain source. In addition to physical therapy and medication for treating SI joint pain, multiple interventional measures including steroid injection, radiofrequency ablation, prolotherapy, and SI joint fusion have been proposed with various efficacies. This article describes the etiology, risk factors, and diagnostic methods as well as the different treatment modalities, focusing on interventional pain management options for patients suffering from SI joint pain.

4-Phenylbutyric acid protects against vasculitic peripheral neuropathy induced by ischaemia-reperfusion through attenuating endoplasmic reticulum stress.

Vasculitic peripheral neuropathy (VPN) is characterized by acute-to-subacute onset of painful sensory and motor disturbances that result from inflammatory obliteration of nerve blood vessels and subsequent ischaemic injury. Endoplasmic reticulum (ER) stress has been implicated in the pathogenesis of various peripheral neuropathies, and 4-phenylbutyric acid (4-PBA) is a chemical chaperone that inhibits ER stress signaling. We investigated the effects of 4-PBA on neuropathic pain associated with VPN induced by ischaemia-reperfusion (IR) and its underlying mechanisms. Male Sprague-Dawley rats were allocated to one of the following groups: sham, sham + 4-PBA, IR, and IR + 4-PBA. IR was achieved by occluding the femoral artery for 4 h followed by reperfusion. The behavioral parameters were assessed, and the expression of ER stress markers and nuclear factor (NF)-κB in sciatic nerves was measured. The behavioral data confirmed that VPN induced by IR leads to hindpaw mechano-allodynia and heat hyperalgesia as well as impaired hindpaw grip strength, indicating the development of neuropathic pain and debilitating symptoms of VPN. The molecular data revealed that VPN induced by IR activated ER stress sensors and effector molecules as well as NF-κB in the sciatic nerves, indicating the involvement of ER stress and NF-κB-mediated neuroinflammation. Notably, 4-PBA significantly reduced the expression of all these markers and improved all behavioral changes induced by IR. This study demonstrated that ER stress and NF-κB-mediated neuroinflammation contribute to VPN induced by IR and that 4-PBA has protective potential against neuropathic pain associated with VPN.

Resveratrol alleviates nuclear factor-κB-mediated neuroinflammation in vasculitic peripheral neuropathy induced by ischaemia-reperfusion via suppressing endoplasmic reticulum stress.

Vasculitic peripheral neuropathy (VPN) arises from an inflammatory obstruction in the blood vessels supplying peripheral nerves and subsequent ischaemic insults, which exhibits the clinical features of neuropathic pain and impaired peripheral nerve function. VPN induced by ischaemia-reperfusion (IR) has been reported to involve nuclear factor-κB (NF-κB)-mediated neuroinflammation. Recent studies have suggested that endoplasmic reticulum (ER) stress has been implicated in the development of peripheral neuropathies. Resveratrol possesses a potent anti-inflammatory capacity. We hypothesized that resveratrol may exert a protective effect against VPN through modulating the interrelated ER stress and NF-κB pathways. Male Sprague-Dawley rats were allocated into five groups: sham, sham + resveratrol 40 mg/kg (R40), IR, IR + R20 and IR + R40. VPN was induced by occluding the right femoral artery for 4 hours followed by reperfusion. Our data have shown that VPN induced by IR led to hind paw mechanical allodynia, heat hyperalgaesia, and impaired motor nerve conduction velocity (MNCV). With resveratrol intervention, the behavioural parameters were improved in a dose-dependent manner and the MNCV levels were increased as well. The molecular data revealed that VPN induced by IR significantly increased the expression of NF-κB as well as the ER stress sensor proteins, protein kinase RNA-like endoplasmic reticulum kinase, inositol-requiring enzyme 1 and activating transcription factor 6 in the sciatic nerves. More importantly, resveratrol significantly attenuated the expression of NF-κB and the ER stress sensor proteins after IR. In conclusion, resveratrol alleviates VPN induced by IR. The mechanisms may involve modulating NF-κB-mediated neuroinflammation via suppressing ER stress.

Increased Subsequent Risk of Coronary Heart Disease in Primary Cesarean Delivery Women: A Population-Based Cohort Study.

BACKGROUND: Impacts of delivery modes on the subsequent risk of coronary heart disease (CHD) in pregnant women have not been elucidated. MATERIALS AND METHODS: Data of women who had undergone cesarean delivery (CD cohort) or vaginal delivery (VD cohort) between January 2000 and December 2012 from Taiwan Health Insurance Database were analyzed. All subjects were tracked until December 31, 2013. For women with multiple deliveries, only the first delivery data were included. Study end point was the diagnosis of new-onset CHD after delivery. RESULTS: In total, 51,765 subjects (CD cohort: n = 17,839; VD cohort: n = 33,926) were included. During 1-14 years of follow-up, the incidence rate of new-onset CHD in the CD cohort was significantly higher than in the VD cohort (1.3% [231/17,839] vs. 0.8% [257/33,926], p < 0.001; effect size: 0.30). Analysis revealed that the subsequent risk of CHD in the CD cohort was significantly higher than in the VD cohort (adjusted hazard ratio [HR] = 1.28, 95% confidence intervals [CI]: 1.06-1.55, p = 0.012). We performed sensitivity tests by excluding subjects who had undergone CD due to nonmedical reasons from the CD cohort. The remaining subjects were named as the *CD cohort. Analysis also revealed a higher subsequent risk of CHD in the *CD cohort than in the VD cohort (adjusted HR = 1.32, 95% CI: 1.08-1.60, p = 0.006). CONCLUSIONS: Women who had undergone primary CD, especially those who had undergone CD due to medical reasons, were associated with an ∼30% higher risk of CHD than those who had undergone VD.