Endoplasmic reticulum stress-mediated autophagy alleviates lipopolysaccharide-induced nucleus pulposus cell pyroptosis by inhibiting CHOP signaling in vitro.

Pyroptosis, a newly discovered pro-inflammatory programmed necrosis of cells, serves as an initiating and promoting event that leads to intervertebral disc (IVD) degeneration (IDD). Endoplasmic reticulum stress (ERS) and autophagy are vital regulatory mechanisms of cellular homeostasis, which is also closely related to IDD. However, the role and relationship of ERS and autophagy in the pyroptosis of nucleus pulposus cell (NPC) are not well understood. In this research, we aimed to elucidate the role and mechanism of ERS-C/EBP homologous protein (CHOP) in lipopolysaccharide (LPS)-induced cell pyroptosis and determine its interaction with autophagy. ERS and autophagy inducers or inhibitors were used or not in the preconditioning of rat NPCs. Cell viability, pyroptosis-related protein expression, caspase-1 activity assay, and enzyme-linked immunosorbent assay were performed to observe rat NPC pyroptosis after the treatment of LPS. Activation of the ERS pathway and autophagy were assessed by quantitative real-time PCR, western blot analyses, and immunofluorescence staining assay to classify the molecular mechanisms. Our results showed that LPS stimulation induced NPC pyroptosis with concomitant activation of the ERS-CHOP pathway and initiated autophagy. Activation of the ERS-CHOP pathway exacerbated rat NPC pyroptosis, whereas autophagy inhibited cell pyroptosis. LPS-induced cell pyroptosis and CHOP upregulation were negatively regulated by autophagy. LPS-induced autophagy was depressed by the ERS inhibitor but aggravated by the ERS inducer. Taken together, our findings suggested that LPS induced NPC pyroptosis by activating ERS-CHOP signaling and ERS mediated LPS-induced autophagy, which in turn alleviated NPC pyroptosis by inhibiting CHOP signaling.

LACC1 regulates changes in the intestinal flora in a mouse model of inflammatory bowel disease.

BACKGROUND: The aim of this study was to explore the mechanism whereby LACC1 regulates the intestinal flora in a mouse model of inflammatory bowel disease (IBD). METHODS: C57BL/6 and Lacc1-/- mice were used to establish a mouse model of IBD induced by dextran sodium sulfate (DSS). The effects of Lacc1 deletion in mice were evaluated. Changes in the body weight and stool blood were recorded daily. After 7 days of successful modeling, the mice were sacrificed, blood was collected from the eyeballs, the entire colon was dissected and separated, and the length of the colon was measured. RESULTS: Compared with the wild-type (WT) DSS model group, the Lacc1-/- DSS model group showed a significantly higher disease activity index score (P < 0.05), significantly faster weight loss (P < 0.05), and a significantly shorter colon (P < 0.05), indicating that the colonic mucosal tissue was seriously damaged in the Lacc1-/- DSS model group (P < 0.05). Serum IL-1ß, IL-6, TNF-α, and IFN-γ levels were significantly higher in the Lacc1-/- DSS model group than the WT DSS model group. Principal coordinate analysis showed that there were significant microbiome differences between the WT, Lacc1-/-, WT DSS model, and Lacc1-/- DSS model groups (P < 0.05). Linear discriminant analysis effect size analysis showed that under natural conditions, Lacc1-/- mice had significant changes in their intestinal flora compared with control mice (LDA value > 3 or < 3, P < 0.05). CONCLUSIONS: Lacc1 deletion aggravates DSS-induced IBD in mice.

A Novel Technique for Treating Early Deep Surgical Site Infection After Posterior Lumbar Fusion with Instrumentation.

OBJECTIVE: To introduce a novel technique of using incisional vacuum-assisted closure (VAC) after 1-stage incision suture combined with closed suction irrigation system (CSIS) for treating early deep surgical site infection (SSI) after posterior lumbar fusion with instrumentation and to compare it with traditional CSIS. METHODS: This was a retrospective study. Patients with early deep SSI after posterior lumbar fusion with instrumentation from January 2013 to May 2020 who were treated by meticulous debridement followed by either CSIS or incisional VAC after 1-stage incision suture combined with CSIS were identified. The demographic characteristics, treatment features, and outcomes were analyzed and compared between the 2 treatment methods. RESULTS: A total of 48 patients (48/5016, 0.96%) developed early deep SSI, 46 of whom were enrolled in this study. This included 24 patients in the CSIS group (group 1) and 22 patients in the incisional VAC after 1-stage incision suture combined with CSIS group (group 2). All patients received follow-up, with an average of 19.7 months (range, 13-30 months). There were no significant differences in demographic characteristics in both groups (P > 0.05). The number of VAC foam dressing or ordinary dressing changes (P < 0.001), number of debridements (P = 0.028), intravenous antibiotic duration (P = 0.042), oral antibiotic duration (P = 0.019), and hospital stay (P = 0.029) in group 1 were significantly higher than those in group 2. The irrigation duration in group 1 was significantly shorter than that in group 2 (P = 0.007). All patients were eventually cured with satisfactory outcomes. CONCLUSIONS: Compared with CSIS, incisional VAC after 1-stage incision suture combined with CSIS may be recommended considering that it has fewer dressing changes, fewer debridements, longer irrigation duration, shorter duration of antibiotic use, shorter hospital stay, and more convenient nursing care.

Risk Factors for Increased Surgical Drain Output After Transforaminal Lumbar Interbody Fusion.

OBJECTIVE: To investigate the risk factors for increased surgical drain output after transforaminal lumbar interbody fusion (TLIF). METHODS: Patients who underwent TLIF in a single center from June 2017 to January 2020 were included in this study. They were divided into the increased surgical drain output group and no increased surgical drain output group according to the boundary of the median drain output. Patients' demographic and clinical parameters were compared between the 2 groups. Risk factors for increased surgical drain output were identified by univariate and multivariate logistic regression analysis. RESULTS: This study enrolled 368 patients who underwent TLIF. Among them, 187 patients had increased surgical drain output (drain output ≥50th percentile or 480 mL). Univariate analysis showed that age (P < 0.001), smoking status (P = 0.002), number of fused levels (P < 0.001), intraoperative blood loss (P < 0.001), intraoperative end plate injury (P < 0.001), administration of tranexamic acid (TXA) (P = 0.002), and surgical duration (P < 0.001) were significantly associated with increased surgical drain output. Multiple logistic regression analysis revealed that older age (P = 0.001), smoking (P = 0.005), more fused levels (P < 0.001), and intraoperative end plate injury (P = 0.017) were the independent risk factors, while administration of TXA (P = 0.012) was a protective factor. CONCLUSIONS: This study showed that older age, smoking, more fused levels, and intraoperative end plate injury were the independent risk factors, while administration of TXA was a protective factor for increased surgical drain output after TLIF.

CTGF Attenuates Tendon-Derived Stem/Progenitor Cell Aging.

Aged tendon-derived stem/progenitor cells (TSPCs) lead to age-related tendon disorders and impair tendon healing. However, the underlying molecular mechanisms of TSPC aging remain largely unknown. Here, we investigated the role of connective tissue growth factor (CTGF) in TSPC aging. CTGF protein and mRNA levels were markedly decreased in the aged TSPCs. Moreover, recombinant CTGF attenuates TSPC aging and restores the age-associated reduction of self-renewal and differentiation of TSPCs. In addition, cell cycle distribution of aged TSPCs was arrested in the G1/S phase while recombinant CTGF treatment promoted G1/S transition. Recombinant CTGF also rescued decreased levels of cyclin D1 and CDK4 and reduced p27kip1 expression in aged TSPCs. Our results demonstrated that CTGF plays a vital role in TSPC aging and might be a potential target for molecular therapy of age-related tendon disorders.

Estimated Financing Amount Needed for Essential Medicines in China, 2014.

BACKGROUND: At the present time, the government is considering to establish the independent financing system for essential medicines (EMs). However, it is still in the exploration phase. The objectives of this study were to calculate and estimate financing amount of EMs in China in 2014 and to provide data evidence for establishing financing mechanism of EMs. METHODS: Two approaches were adopted in this study. First, we used a retrospective research to estimate the cost of EMs in China in 2014. We identified all the 520 drugs listed in the latest national EMs list (2012) and calculated the total sales amount of these drugs in 2014. The other approach included the steps that first selecting the 109 most common diseases in China, then identifying the EMs used to treat them, and finally estimating the total cost of these drugs. RESULTS: The results of the two methods, which showed the estimated financing amounts of EMs in China in 2014, were 17,776.44 million USD and 19,094.09 million USD, respectively. CONCLUSIONS: Comparing these two results, we concluded that the annual budget needed to provide for the EMs in China would be about 20 billion USD. Our study also indicated that the irrational drug use continued to plague the health system with intravenous fluids and antibiotics being the typical examples, as observed in other studies.