Andrographolide inhibits secretagogue-induced pseudo-allergic reaction.

Many kinds of drugs induce pseudo-allergic reactions due to activation of mast cells. We investigated the anti-pseudo-allergic effect of andrographolide (Andro). The effects of Andro on pseudo-allergic reactions were investigated in vivo and in vitro. Andro suppressed compound 48/80 (C48/80) induced pseudo-allergic reactions in mice in a dose-dependent manner. Andro also inhibited C48/80-induced local inflammatory reactions in mice. In vitro studies revealed that Andro reduced C48/80-induced mast cells degranulation. Human phospho-kinase array kit and western blotting showed that Andro could inhibit pseudo-allergic responses via the calcium signaling pathway.

LncRBA GSA5, up-regulated by ox-LDL, aggravates inflammatory response and MMP expression in THP-1 macrophages by acting like a sponge for miR-221.

Atherosclerosis is a chronic inflammatory process, plaque rupture and subsequent thrombosis underline the major causes of acute cardio-cerebral vascular diseases. Long non-coding RNAs (lncRNAs) participate in diverse pathologic processes, including inflammation and myocardial infarction. Recent study confirmed the elevation of lncRNA growth arrest-specific 5 (GAS5) in atherosclerotic rats. In this study, we aimed to explore the role and mechanism of GAS5 in the progression of atherosclerotic plaque. Here, expression of GAS5 was enriched in atherosclerotic plaques and THP-1 macrophage exposed to oxidized low-density lipoprotein (ox-LDL). Furthermore, overexpression of GAS5 aggravated ox-LDL-induced pro-inflammatory cytokines (IL-6, IL-1ß, TNF-α) and chemokine MCP-1 secretion in macrophages, which were reversed after GAS5 cessation. Additionally, high expression and secretion of MMP-2 and MMP-9 were increased in ox-LDL-stimulated macrophages following GAS5 elevation, but these increases were inhibited in GAS5-silenced group. Mechanism analysis identified GAS5 as a endogenous sponge to directly bind and suppress miR-221 expression. Notably, miR-221 elevation antagonized GAS5-enhanced inflammatory response and MMPs in macrophages upon ox-LDL. These results suggest that GAS5 can trigger inflammatory response and MMP expression by acting as a sponge of miR-221, which may facilitate fibrous cap degradation and aggravate atherosclerotic plaque destabilization, supporting a promising therapeutic agent against atherosclerosis.

Burnout and job stress of anesthesiologists in the tertiary class A hospitals in Northwest China: A cross-sectional design.

Purpose: Our purpose was to assess job stress and burnout among anesthesiologists in the tertiary class A hospitals in Northwest China, analyze the possible causes and adverse consequences of increased job stress and burnout of anesthesiologists in this region, and put forward suggestions in combination with the current national policies. Methods: We sent 500 electronic questionnaires to all anesthesiologists practicing in the tertiary class A hospitals in Northwest China from 1960 to 2017 on April 2020. A total of 336 (67.2%) questionnaires were returned and could be used for analysis. Burnout and job stress were assessed by using the modified Maslach Burnout Inventory-Human Services Survey and Chinese Perceived Stress Scale, respectively. Results: First, as for emotional exhaustion, the situations of anesthesiologists with different working years and workloads are different with statistical significance (P < 0.05). Second, as for depersonalization, the situations of anesthesiologists with different ages, professional titles, working years, physical health status, and workload are different (P < 0.05). Third, as for personal accomplishment, the situations of anesthesiologists with different physical health status are different (P < 0.05). Finally, the regression results showed that the longer the fatigue working years and the worse the physical health of anesthesiologists in Northwest China, the more likely these two factors were to cause burnout (P < 0.05), as for job stress, there was a negative correlation between job stress and physical health status (P < 0.05). Conclusion: Burnout and high job pressure are common among anesthesiologists in tertiary class A hospitals in Northwest China. We should focus on the allocation of labor intensity, pay attention to the physical and mental health of employees, establish targeted incentive mechanism, and improve the system of promotion and income rises for grassroots doctors. This may be not only conducive to the quality of medical care for patients but also conducive to the development of anesthesiology in China. Trial registration: Identifier: ChiCTR2000031316.

[Application of sliding osteotomy in total knee arthroplasty for patients with extra-articular femoral deformity].

OBJECTIVE: In order to observe the clinical effects of sliding osteotomy for patients with severe knee osteoarthritis and varus knee due to complex femoral extra-articular deformity to achieve the medial and lateral soft tissue balancing during total knee arthroplasty. METHODS: From June 2014 to January 2018, a total of 22 patients with severe knee osteoarthritis and complex extra-articular malformation of femurs were treated with total knee arthroplasty. There were 5 males and 17 females in this group, aged 48 to 76 years old, with an average age of (61.3±13.8) years old. All the patients had varus deformities caused by extra-articular deformities of femur. Hip-knee-ankle(HKA) angle was(158.8±9.7) ° before operation, and the average Knee Society Score (KSS) clinical score was 32.6±6.1;KSS function score was 35.8 ±9.6;the average Hospital for Special Surgical (HSS) score was 39.7±4.6;the average range of motion before operation was (80.6±10.7) °. The mechanical alignment method was used in joint replacement. The flexion space was balanced first. The coronal plane vertical sliding osteotomy was performed on the medial femoral condyle for the imbalance of coronal plane. The sliding distance of the osteotomy block was determined by straightening the gap between the inner and outer sides of the space until the space was balanced. After the separated segments were fixed with several screws, the prosthesis was installed as usual. RESULTS: The wounds of all patients healed in the first stage, and no wound complications occurred. All the 22 patients were followed up, and the duration ranged from 18 months to 3 years with an average of (28.2±10.1) months. X-ray showed that the fracture line disappeared for 2 to 5(3.5±1.5) months without nonunion. HKA angle measured at the latest follow up was (178.8±0.7) °, which wassignificantly different from that before operation. The HSS score was 91.3 ±6.0;KSS clinical score 93.7±3.5;KSS functional score 81.2±6.5;and the average range of motion of knee joint was(121.7±11.6) °, which was statistically significant compared with that before operation. CONCLUSION: For severe knee osteoarthritis patients with complex femoral extra-articular deformity, sliding osteotomy is performed. For severe varus deformity, downward sliding the medial femoral condyle is performed. The operation is relatively simple and the damage is small. It is easy to achieve the balance of internal and external soft tissue in flexion extension space. The short-term clinical effect is satisfactory.

Lipopolysaccharide-induced expression of astrocyte elevated gene-1 promotes degeneration and inflammation of chondrocytes via activation of nuclear factor-κB signaling.

Osteoarthritis is an inflammatory disease characterized by joint degeneration and inflammation. Astrocyte elevated gene-1 (AEG-1) has been suggested as a novel inflammation-related factor in the pathological processes of various inflammatory diseases. To date, little is known about the role of AEG-1 in osteoarthritis. The aim of the present study was to explore the potential role of AEG-1 in the regulation of lipopolysaccharide-induced apoptosis and inflammation of chondrocytes. The results showed that AEG-1 expression was significantly upregulated in chondrocytes following exposure to lipopolysaccharide. Knockdown of AEG-1 increased the survival and decreased the expression of matrix metalloproteinases in chondrocytes treated with lipopolysaccharide. Moreover, silencing of AEG-1 restricted the lipopolysaccharide-induced production of proinflammatory cytokines. In contrast, AEG-1 overexpression caused opposite effects. Notably, we found that AEG-1 inhibition blocked the lipopolysaccharide-induced activation of nuclear factor-κB signaling through impeding the nuclear translocation of nuclear factor-κB p65 subunit. Additionally, inhibition of nuclear factor-κB partially reversed the AEG-1-mediated promotion of lipopolysaccharide-induced inflammatory injury in chondrocytes. In conclusion, our results demonstrate that inhibition of AEG-1 expression attenuates lipopolysaccharide-induced degeneration and inflammation of chondrocytes through suppressing the activation of nuclear factor-κB signaling. This work therefore highlights a potential role of AEG-1 in the pathogenesis of osteoarthritis, and indicates its potential as a therapeutic target.

The Effect of Dexmedetomidine Added to Preemptive Ropivacaine Infiltration on Postoperative Pain After Lumbar Fusion Surgery: A Randomized Controlled Trial.

STUDY DESIGN: A prospective and controlled study of dexmedetomidine added to preemptive ropivacaine infiltration in lumbar fusion surgery. OBJECTIVE: Assessment of dexmedetomidine added to preemptive ropivacaine infiltration for the relief of postoperative pain after lumbar fusion surgery. SUMMARY OF BACKGROUND DATA: Single local anesthetic preemptive wound infiltration for the relief of postoperative pain does not translate into major or consistent clinical benefits after lumbar fusion surgery. Dexmedetomidine added to local anesthetics prolonged the duration of blockade and enhanced the analgesic in peripheral nerve block. The effect of dexmedetomidine added to preemptive ropivacaine infiltration in lumbar fusion surgery for the relief of postoperative pain has yet not been studied. METHODS: Fifty-seven patients with elective posterior lumbar fusion were randomly divided into two groups. Five minutes before incision, the skin and subcutaneous tissues were injected with 20 mL 0.5% ropivacaine in group R (n = 28) and 20 mL 0.5% ropivacaine and 1 ug/kg of dexmedetomidine in group RD (n = 29) in two divided doses (i.e., 10 mL per side of the incision line). After the operation, all patients received intravenous morphine for analgesia. The total morphine consumption, the time of first analgesic demand, numbers of PCA analgesia, Visual Analog Scale, and postoperative adverse effects were collected. RESULTS: In group RD, cumulative morphine dose and numbers of PCA analgesia in group RD were significantly reduced, the time of first analgesic demand was significantly delayed compared to the group R. Visual Analog Scale in group RD showed a marked reduction at 8 hours, 12 hours, 16 hours after operation and less patients in group RD experienced postoperative nausea or vomiting compared to the group R. CONCLUSION: The addition of dexmedetomidine to preemptive ropivacaine wound infiltration provided a superior analgesic effect, reduced postoperative morphine consumption, and prolonged the time of the first analgesic demand with no serious side effects. LEVEL OF EVIDENCE: 2.

Genetic effects of BDKRB2 and KNG1 on deep venous thrombosis after orthopedic surgery and the potential mediator.

Deep venous thrombosis (DVT) is a common complication of orthopedic surgery. Genetic risk factors and high heritability carried a substantial risk of DVT. In this study, we aimed to investigate the potential association in the Han Chinese population between the polymorphisms of BDKRB2 and KNG1 and DVT after orthopedic surgery (DVTAOS). A total of 3,010 study subjects comprising 892 DVT cases and 2,118 controls were included in the study, and 39 single nucleotide polymorphisms (SNPs) in total (30 for BDKRB2 and 9 for KNG1) were chosen for genotyping. Two SNPs, rs710446 (OR = 1.27, P = 0.00016) and rs2069588 (OR = 1.29, P = 0.00056), were identified as significantly associated with DVTAOS. After adjusting for BMI, the significance of rs2069588 decreased (P = 0.0013). Haplotype analyses showed that an LD block containing rs2069588 significantly correlated with the DVTAOS risk. Moreover, bioinformatics analysis indicated that hsa-miR-758-5p and BDKRB2 formed miRNA/SNP target duplexes if the rs2069588 allele was in the T form, suggesting that rs2069588 may alter BDKRB2 expression by affecting hsa-miR-758-5p/single-nucleotide polymorphism target duplexes. Our results demonstrate additional evidence supporting that there is an important role for the KNG1 and BDKRB2 genes in the increased susceptibility of DVTAOS.

[Application of improved precision alignment method of lower limbs mechanical alignment on open wedge high tibial osteotomy].

Objective: To evaluate the effects of the improved precision alignment method of lower limbs mecha-nical alignment for osteoarthritis of the knee in open wedge high tibial osteotomy (OWHTO). Methods: A retrospective analysis was made on the clinical data of 62 patients (68 knees) with knee osteoarthritis in the medial compartment treated with OWHTO between January 2012 and December 2015 who accorded with the inclusion criteria. The traditional method for positioning lower limb mechanical force line was used in 29 cases (32 knees) (traditional group), and improved method for positioning lower limb mechanical force line in 33 cases (36 knees) (modified group). There was no significant difference in gender, age, side, course of disease, and osteoarthritis grading between two groups ( P>0.05) with comparable. The operation time, intraoperative fluoroscopy times, and intraoperative blood loss were recorded in two groups; Before and after operation, the lower limb mechanical force line was observed on the X-ray films, which was expressed by hip-knee-ankle angle (HKA). The clinical efficacy was evaluated by the American Hospital for Special Surgery (HSS) score, and the Western Ontario and McMaster University Osteoarthritis Index (WOMAC). Results: Incision hematoma occurred in 1 case of traditional group and was cured at 3 weeks after symptomatic treatment; and primary healing was obtained in the other patients, with no early complications. The operation time and intraoperative fluoroscopy times of the modified group were significantly lower than those of the traditional group ( t=11.934, P=0.000; t=11.663, P=0.000), but there was no significant difference in blood loss between the two groups ( t=0.209, P=0.835). The patients were followed up for 6 to 24 months (mean, 12.7 months) in the traditional group and for 3 to 22 months (mean, 13.2 months) in the modified group. The medial knee pain disappeared in all patients. At last follow-up, the HSS score and WOMAC score were significantly improved when compared with preoperative scores in two groups ( P<0.05), but there was no significant difference between the two groups ( P>0.05). Postoperative X-ray examination showed that the tibiofemoral angle was corrected in the two groups. The HKA angle at immediate after operation and last follow-up was significantly higher than angle at pre-operation in two groups ( P<0.05), but there was no significant difference between at immediate after operation and at last follow-up ( P>0.05). Conclusion: Compared with the traditional method for positioning lower limb mechanical force line, the improved precision alignment method can reduce the times of intraoperative fluoroscopy and shorten the operation time, which reduces the radiation exposure of both doctors and patients.

Association between ACE polymorphisms and osteoarthritis susceptibility.

OBJECTIVE: The present study was designed to investigate the association of angiotensin-converting enzyme (ACE) rs4343 and rs4362 polymorphisms with the susceptibility to osteoarthritis (OA). METHODS: 109 knee OA patients and 114 healthy people were enrolled in the study. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was used to perform the genotyping for two groups and the linkage disequilibrium and haplotype were analyzed using Haploview software. The differences of genotype and allele frequencies were analyzed by χ(2) test and Fisher's exact test. The relationship between ACE polymorphisms and OA susceptibility was represented by odds ratios (ORs) with 95% confidence intervals (95% CIs). RESULTS: The genotypes distributions of ACE rs4343 and rs4362 polymorphisms in control groups were accordance with HWE. ACE rs4343 polymorphism was associated with the significantly increased risk of OA (AG vs. AA: OR=2.41, P=0.003; GG vs. AA: OR=5.35, P=0.015; G vs. A: OR=2.27, P<0.001). Similarly, rs4362 polymorphisms was also a risk factor for OA (CT vs. CC: OR=2.60, P=0.005; TT vs. CC: OR=3.15, P=0.003; T vs. C: OR=1.88, P=0.001). The result of haplotype analysis showed complete linkage disequilibrium in rs 4343 and rs 4362 polymorphisms. The G-T haplotype significantly increased OA susceptibility, but A-C is a protective factor for the occurrence of OA. CONCLUSION: Significant correlation exists between ACE rs4343 and rs4362 polymorphisms and OA. In haplotype analysis, A-C haplotype may provide protection against OA, and G-T haplotype may be a risk factor for the development of OA.