关节镜下半月板成形术对膝关节半月板损伤患者血清疼痛因子、一氧化氮、透明质酸及关节活动度的影响

目的探讨关节镜下半月板成形术(AMP)对膝关节半月板损伤患者血清疼痛因子、一氧化氮(NO)、透明质酸(HA)及关节活动度的影响。方法选取2019年5月—2020年12月收治的90例膝关节半月板损伤为研究对象,根据治疗方法不同分为对照组和治疗组,每组45例。对照组接受保守治疗,治疗组行AMP治疗。比较两组的临床疗效,治疗前后的血清前列腺素E₂(PGE₂)、5-羟色胺(5-HT)、NO、HA、疼痛视觉模拟评分法(VAS)评分和膝关节活动度。记录两组治疗并发症发生情况。结果治疗组疗效优良率高于对照组(P<0.05)。治疗后,两组血清PGE₂、5-HT、NO、HA水平均较治疗前下降,且治疗组低于对照组(P<0.05)。治疗后1、2、3、4周,两组VAS评分均较治疗前降低,且治疗组低于对照组(P<0.05)。治疗后,两组膝关节屈伸活动度均较治疗前升高,且治疗组高于对照组(P<0.05)。两组并发症发生率比较差异无统计学意义(P>0.05)。结论AMP对膝关节半月板损伤疗效良好,可减少疼痛因子生成,控制NO、HA水平,提高关节活动度。     

Estimating Cost-Effectiveness Using Alternative Preference-Based Scores and Within-Trial Methods: Exploring the Dynamics of the Quality-Adjusted Life-Year Using the EQ-5D 5-Level Version and Recovering Quality of Life Utility Index

ObjectivesThis study aimed to explore quality-adjusted life-year (QALY) and subsequent cost-effectiveness estimates based on the more physical health–focused EQ-5D 5-level version (EQ-5D-5L) value set for England or cross-walked EQ-5D 3-level version UK value set scores or more mental health recovery-focused Recovering Quality of Life Utility Index (ReQoL-UI), when using alternative within-trial statistical methods. We describe possible reasons for the different QALY estimates based on the interaction between item scores, health state profiles, preference-based scores, and mathematical and statistical methods chosen.MethodsQALYs are calculated over 8 weeks from a case study 2:1 (intervention:control) randomized controlled trial in patients with anxiety or depression. Complete case and with missing cases imputed using multiple-imputation analyses are conducted, using unadjusted and regression baseline-adjusted QALYs. Cost-effectiveness is judged using incremental cost-effectiveness ratios and acceptability curves. We use previously established psychometric results to reflect on estimated QALYs.ResultsA total of 361 people (241:120) were randomized. EQ-5D-5L crosswalk produced higher incremental QALYs than the value set for England or ReQoL-UI, which produced similar unadjusted QALYs, but contrasting baseline-adjusted QALYs. Probability of cost-effectiveness <£30 000 per QALY ranged from 6% (complete case ReQoL-UI baseline-adjusted QALYs) to 64.3% (multiple-imputation EQ-5D-5L crosswalk unadjusted QALYs). The control arm improved more on average than the intervention arm on the ReQoL-UI, a result not mirrored on the EQ-5D-5L nor condition-specific (Patient-Health Questionnaire-9, depression; Generalized Anxiety Disorder-7, anxiety) measures.ConclusionsReQoL-UI produced contradictory cost-effectiveness results relative to the EQ-5D-5L. The EQ-5D-5L’s better responsiveness and “anxiety/depression” and “usual activities” items drove the incremental QALY results. The ReQoL-UI’s single physical health item and “personal recovery” construct may have influenced its lower 8-week incremental QALY estimates in this patient sample.     

Do social support and community engagement act as mechanisms in the association between neighbourhood income inequality and the mental health of mothers in Calgary,Canada? A mediation analysis

PurposeAccording to the social determinants of health framework, income inequality is a potential risk factor for adverse mental health. However, few studies have explored the mechanisms suspected to mediate this relationship. The current study addresses this gap through a mediation analysis to determine if social support and community engagement act as mediators linking neighbourhood income inequality to maternal anxiety and depressive symptoms within a cohort of new mothers living in the City of Calgary, Canada.MethodsData collected at three years postpartum from mothers belonging to the All Our Families (AOF) cohort were used in the current study. Maternal data were collected between 2012 and 2015 and linked to neighbourhood socioeconomic data from the 2006 Canadian Census. Income inequality was measured using Gini coefficients derived from 2006 after-tax census data. Generalized structural equation models were used to quantify the associations between income inequality and mental health symptoms, and to assess the potential direct and indirect mediating effects of maternal social support and community engagement.ResultsIncome inequality was not significantly associated with higher depressive symptoms (β = 0.32, 95%CI = −0.067, 0.70), anxiety symptoms (β = 0.11, 95%CI = −0.39, 0.60), or lower social support. Income inequality was not associated with community engagement. For the depression models, higher social support was significantly associated with lower depressive symptoms (β = −0.13, 95%CI = −0.15, −0.097), while community engagement was not significantly associated with depressive symptoms (β = 0.059, 95%CI = −0.15, 0.27). Similarly, for the anxiety models, lower anxiety symptoms were significantly associated with higher levels of social support (β = −0.17, 95%CI = −0.20, −0.13) but not with higher levels of community engagement (β = 0.14, 95%CI = −0.14, 0.41).ConclusionThe current study did not find clear evidence for social support or community engagement mediating the relationship between neighbourhood income inequality and maternal mental health. Future investigations should employ a broader longitudinal approach to capture changes in income inequality, potential mediators, and mental health symptomatology over time.     

Potentilla anserine L. polysaccharide protects against cadmium-induced neurotoxicity

Cadmium is a toxic metal that can damage the brain and other organs. This study aimed to explore the protective effects of Potentilla anserine L. polysaccharide (PAP) against CdCl₂-induced neurotoxicity in N2a and SH-SY5Y cells and in the cerebral cortex of BALB/c mice. In addition, we aimed to identify the potential mechanisms underlying these protective effects. Relative to CdCl₂ treatment alone, pretreatment with PAP prevented the reduction in cell viability evoked by CdCl₂, decreased rates of apoptosis, promoted calcium homeostasis, decreased ROS accumulation, increased mitochondrial membrane potential, inhibited cytochrome C and AIF release, and prevented the cleavage of caspase-3 and PARP. In addition, PAP significantly decreased the CdCl₂-induced phosphorylation of CaMKII, Akt, and mTOR. In conclusion, PAP represents a potential therapeutic agent for the treatment of Cd-induced neurotoxicity, functioning in part via attenuating the activation of the mitochondrial apoptosis pathway and the Ca²⁺-CaMKII-dependent Akt/mTOR pathway.     

Metabolism of non-steroidal anti-inflammatory drugs (NSAIDs) by Streptomyces griseolus CYP105A1 and its variants

In the field of drug development, technology for producing human metabolites at a low cost is required. In this study, we explored the possibility of using prokaryotic water-soluble cytochrome P450 (CYP) to produce human metabolites. Streptomyces griseolus CYP105A1 metabolizes various non-steroidal anti-inflammatory drugs (NSAIDs), including diclofenac, mefenamic acid, flufenamic acid, tolfenamic acid, meclofenamic acid, and ibuprofen. CYP105A1 showed 4′-hydroxylation activity towards diclofenac, mefenamic acid, flufenamic acid, tolfenamic acid, and meclofenamic acid. It should be noted that this reaction specificity was similar to that of human CYP2C9. In the case of mefenamic acid, another metabolite, 3′-hydroxymethyl mefenamic acid, was detected as a major metabolite. Substitution of Arg at position 73 with Ala in CYP105A1 dramatically reduced the hydroxylation activity toward diclofenac, flufenamic acid, and ibuprofen, indicating that Arg73 is essential for the hydroxylation of these substrates. In contrast, substitution of Arg84 with Ala remarkably increased the hydroxylation activity towards diclofenac, mefenamic acid, and flufenamic acid. Recombinant Rhodococcus erythrocyte cells expressing the CYP105A1 variant R84A/M239A showed complete conversion of diclofenac into 4′-hydroxydiclofenac. These results suggest the usefulness of recombinant R. erythropolis cells expressing actinomycete CYP, such as CYP105A1, for the production of human drug metabolites.     

Optical coherence tomography angiography in the evaluation of vascular patterns of ocular surface squamous neoplasia during topical medical treatment

PurposeOptical coherence tomography angiography (OCTA) was utilized to examine changes in ocular surface squamous neoplasia (OSSN) vascular patterns over time in individuals treated with topical medical therapy.MethodsTen individuals with OSSN diagnosed by clinical examination and high resolution (HR)-optical coherence tomography (OCT) were recruited. All individuals received topical immuno- or chemotherapy. OCTA images were obtained and analyzed at three points: presentation, mid-treatment and tumor resolution. Tumor metrics including tumor area (TA), tumor volume (TV), tumor depth (TD), and total tumor density (TTD) were calculated. Vessel area density (VAD) was also quantified within the OSSN, the subepithelium under and adjacent to the OSSN and the subepithelium of the uninvolved, contralateral eye. Vascular network changes were also subjectively evaluated.ResultsTA, TV, TD and TTD all significantly decreased with time (p < 0.001). The mean VAD within the OSSN significantly decreased (p < 0.001) between visits (presentation: 26.52 ± 6.8%, mid-treatment: 7.19 ± 5.88%, tumor resolution: 0.11 ± 0.34%). The mean subepithelial VAD under the OSSN also decreased with time (23.22 ± 11.03%, 20.99 ± 5.99% and 19.58 ± 7.08%), and after resolution the sub-tumor VAD (19.58 ± 7.08%) was comparable to the subepithelial VAD in the contralateral eye (15.47 ± 4.37%, p > 0.05). The mean VAD in the subepithelium adjacent to the OSSN increased with treatment, then decreased significantly between mid-treatment and resolution (23.26 ± 4.54, 28.30 ± 7.43% and 21.68 ± 6.10%, p = 0.009). Qualitatively, the tumor subepithelial vascular network was complex and dense but with tumor resolution appeared less tortuous and similar to the uninvolved eye.ConclusionOCTA provided insight into the pathophysiology of tumor angiogenesis, showing decreased vascular density and normalization of vascular networks associated with tumor resolution.