Correction: Duhuo Jisheng Decoction regulates intracellular zinc homeostasis by enhancing autophagy via PTEN/Akt/mTOR pathway to improve knee cartilage degeneration.

[This corrects the article DOI: 10.1371/journal.pone.0290925.].

Duhuo Jisheng Decoction regulates intracellular zinc homeostasis by enhancing autophagy via PTEN/Akt/mTOR pathway to improve knee cartilage degeneration.

BACKGROUND: Articular cartilage and cartilage matrix degradation are key pathological changes occurring in the early stage of knee osteoarthritis (KOA). However, currently, there are limited strategies for early prevention and treatment of KOA. Duhuo Jisheng Decoction (DHJSD) is a formula quoted in Bei Ji Qian jin Yao Fang, which was compiled by Sun Simiao in the Tang Dynasty of China. As a complementary therapy, it is widely used to treat early-stage KOA in China; however, its mechanism has not been completely elucidated. OBJECTIVE: This study investigated the potential role of DHJSD in preventing cartilage degradation and the underlying mechanism. METHODS: A rat model of KOA model was established via the Hulth method. Subsequently, 25 rats were randomized into sham (saline), model control (saline), high-DHJSD (1.9g/mL of DHJSD), medium-DHJSD (1.2g/mL of DHJSD), and low-DHJSD groups (0.6g/mL of DHJSD). After 4 weeks of treatment, all rats were sacrificed and the severity of the cartilage degeneration was evaluated by a series of histological methods. The autophagosome was observed using transmission electron microscopy, and the related functional proteins were detected by the western blotting and real-time polymerase chain reaction. Next, the mechanism by which DHJSD improves knee cartilage degeneration was further clarified the in vitro by gene silencing technology combined with a series of functional experiments. The proteins levels of PTEN, Akt, p-Akt, mTOR, and p-mTOR, as well as the marker proteins of autophagy and apoptosis were determined. Zinc levels in chondrocytes were determined using inductively coupled plasma mass spectrometry. RESULTS: Histopathological staining revealed that DHJSD had a protective effect on the cartilage. DHJSD increased autophagosome synthesis and the expression of autophagy proteins LC3 and Beclin-1 in chondrocytes. Moreover, it reduced the phosphorylation levels of Akt and mTOR and the levels of zinc, MMP-13, Bax, and Bcl-2. Following PTEN silencing, this DHJSD-mediated reduction in Akt and mTOR phosphorylation and Bax, Bcl-2, and zinc levels were further decreased; in addition, DHJSD-mediated increase in LC3 and Beclin-1 levels was decreased. CONCLUSION: DHJSD inhibits the Akt/mTOR signaling pathway by targeting PTEN to promote autophagy in chondrocytes, which may help reduce MMP-13 production by regulating zinc levels in chondrocytes.

The effect of ultrasound-guided acupotomy and Juanbi decoction on lumbar disc herniation: A randomized controlled trial.

BACKGROUND: Acupotomy as well as Juanbi decoction has been used in the treatment of lumbar disc herniation. However, there is no study on ultrasound-guided acupotomy combined with Juanbi decoction in the treatment of lumbar disc herniation. METHOD: This study was supported by the Sichuan Provincial Administration of Traditional Chinese Medicine [grant number: 2020LC0163] and the Science and Technology Department of Sichuan Province [grant number: 2022YFS0418]. This study was 3 center, open, randomized, controlled trial, and was carried out from December 2020 to December 2022. A total of 60 eligible patients with LDH were split into group A and group B at random. The group B received Juanbi Decoction 3 times daily for 2 weeks along with an acupotomy assisted by ultrasound. The acupotomy was administered once a week. The same protocol was used with the group A, but the Juanbi Decoction was replaced with normal saline. OBSERVATION INDEX: Visual analogue scale (VAS) score on 1 day and 1 week after treatment, VAS score, Japanese orthopedic association low back pain score(JOA) rate, Oswestry Disability Index (ODI), and low back outcome scale (LBOS) at 1, 3, 6, and 12 months after treatment in 2 groups. RESULTS: There were no significant differences in general information, VAS score before treatment, JOA, ODI, and LBOS between the 2 groups (P > .05). Intra-group comparison: VAS score, JOA rate, ODI, and LBOS were compared before and after treatment in both groups, and the differences were statistically significant (P < .05). There were significant differences in VAS and LBOS between the 2 groups at 3 and 6 months after treatment, and there were statistically significant differences in ODI and JOA rates at 3, 6, and 12 months after treatment between the 2 groups. CONCLUSION: Acupotomy aided by ultrasound combined with Juanbi Decoction significantly relieves lumbar pain and can improve lumbar function in patients with LDH, and the clinical efficacy lasts for about 6 months.

Age and risk for depression among the elderly: a meta-analysis of the published literature.

OBJECTIVE: The goal of this study was to determine the relationship between age and risk for depression among the old and the oldest old. Method MEDLINE, EMBASE, and the Cochrane Library database were used to identify potential studies. The studies were divided into cross-sectional and longitudinal subsets. For each study, the numbers of the total participants, cases (for cross-sectional study), or incident cases (for longitudinal study) of depression in each age group were extracted and entered into Review Manager 4.2 software. Qualitative meta-analyses of cross-sectional studies and of longitudinal studies were performed. For prevalence and incidence rates of depression, odds risk (OR) and relative risk (RR) were calculated, respectively. RESULTS: The qualitative meta-analyses showed that, compared with younger participants (above vs. below 65 years, above vs. below 70 years, above vs. below 75 years, and above vs. below 80 years), older age groups had a significantly higher risk for depression. (All of the ORs and RRs were significant.) Compared with participants aged 55-89, those aged above 90 years had no higher risk for depression. (Neither the OR nor the RR was significant.) CONCLUSIONS: Despite the methodological limitations of this meta-analysis, older age appears to be an important risk factor for depression in the general elderly population (aged below 80 years), but not in the oldest population (aged above 85 years).

Cognitive function and risk for depression in old age: a meta-analysis of published literature.

BACKGROUND: We assessed the relationship between cognitive impairment (including mild cognitive impairment with no signs of dementia, and dementia) and risk for depression in old age (60 years and older). METHODS: MEDLINE, EMBASE and the Cochrane Library database were used to identify potential studies. All of the clinical studies that produced data on the association between cognitive function and risk of depression among individuals aged 55 years or older were identified and included in this review. The studies were classified into cross-sectional and longitudinal subsets. The quantitative meta-analysis of cross-sectional and longitudinal studies were performed. For prevalence and incidence rates of depression, odds risk (OR) and relative risk (RR) were calculated, respectively. RESULTS: Since all but two studies found in the search were for individuals aged 60 years or over, we assessed and reported on results for this larger group only. In this review we included 13 cross-sectional and four prospective longitudinal studies. The quantitative meta-analysis showed that, in old age, individuals with non-dementia cognitive impairment had neither significant higher prevalence nor incidence rates of depression than those without (odds risk (OR): 1.48, 95% confidence intervals (95% CI): 0.87-2.52; relative risk (RR): 1.12, 95% CI: 0.62-2.01). In old age, individuals with dementia had both significant higher prevalence and incidence rates of depression than those without (OR: 1.82, 95% CI: 1.15-2.89; RR: 3.92, 95% CI: 1.93-7.99). CONCLUSIONS: Despite the methodological limitations of this meta-analysis, we found that in old age, there was no association between depression and cognitive impairment with no dementia; however, there was a definite association between depression and dementia and thus dementia might be a risk for depression.

The biomechanical effect of the relevant segments after facet-disectomy in different diameters under posterior lumbar percutaneous endoscopes: a three-dimensional finite element analysis.

OBJECTIVE: To evaluate the biomechanical influence after percutaneous endoscopic lumbar facetectomy in different diameters on segmental range of motion (ROM) and intradiscal pressure (IDP) of the relevant segments by establishing three dimensional finite element (FE) model. METHODS: An intact L3-5 model was successfully constructed from the CT of a healthy volunteer as Model A (MA). The Model B (MB), Model C (MC) and Model D (MD) were obtained through facetectomy on L4 inferior facet in diameters 7.5 mm, 10 mm and 15 mm on MA for simulation. The ROM and IDP of L3/4 and L4/5 of four models were all compared in forward flexion, backward extension, left and right bending, left and right rotation. RESULTS: Compared with MA, the ROM of L4/5 of MB, MC and MD all increased. MD changed more significantly than MB and MC in backward extension, right bending and right rotation. But that of MB and MC on L3/4 had no prominent change, while MD had a slight increase in backward extension. The IDP of MB and MC on L4/5 in six states was similar to MA, yet MD increased obviously in backward extension, right bending, left and right rotation. The IDP on L3/4 of MB and MC was resemble to MA in six conditions, nevertheless MD increased slightly only in backward extension. CONCLUSION: Compared with the facetectomy in diameters 7.5 mm and 10 mm, the mechanical effect brought by facetectomy in diameter 15 mm on the operating segment changed more significantly, and had a corresponding effect on the adjacent segments.

Effect of Percutaneous Endoscopic Lumbar Foraminoplasty of Different Facet Joint Portions on Lumbar Biomechanics: A Finite Element Analysis.

OBJECTIVE: To evaluate the influence of percutaneous endoscopic lumbar foraminoplasty of different facet joint portions on segmental range of motion (ROM) and intradiscal pressure (IDP) of L3 /L4 and L4 /L5 motion segments by establishing three dimensional finite element (FE) model. METHOD: Computed tomography images of a male adult volunteer of appropriate age and in good condition both mentally and physically. Obtained data was used in this study from July 2020 to December 2020, and an intact L3-5 three dimensional finite element model was successfully constructed using ANSYS and MIMICS software (model M1). The M1 was modified to simulate the foraminoplasty of different facet joint portions, with unilateral cylindrical excision (diameter = 0.75 cm) performed on the tip (model M2) and the base (model M3) of right L5 superior facet elements along with surrounding capsular ligaments, respectively. Under the same loading conditions, the ROM and IDP of L3 /4 and L4 /L5 segments in states of forward flexion, backward extension, left lateral bending, right lateral bending, left axial rotation and right axial rotation were all compared. RESULT: Compared with the intact model in backward extension, M2 increased the ROM of L4/5 segment by 9.4% and IDP by 11.7%, while the ROM and IDP of M3 changed only slightly. In right axial rotation, M2 and M3 increased the ROM of L4/5 segment by 17.9% and by 3.6%, respectively. In left axial rotation, M2 and M3 increased the ROM of L4 /L5 segment by 7.14% and 3.6%, respectively. As for other states including forward flexion, left lateral bending, right lateral bending, the ROM and IDP were not significantly distinct between these two models. While focusing on L3 /L4 segment, obviously changes in the ROM and IDP have not been presented and neither M2 nor M3 changed in any loading condition. CONCLUSION: This study provides evidence that the base-facet foraminoplasty of L5 superior facet provided a higher segmental stability compared with the tip-facet foraminoplasty in flexion and axial rotation. Meanwhile, it also shows the two types of foraminoplasty make few differences to the L4/5 segmental biomechanics. Besides, it does not appear to impact the stability of L3 /L4 in six states of forward flexion, backward extension, left lateral bending, right lateral bending, left axial rotation and right axial rotation when superior facet of L5 was partially removed. These findings might be useful in understanding biomechanics of the lumbar spine after foraminoplasty performed on different portions of the facet, thus providing endoscopic surgeons a better reference for operational approach to maintain the function and mobility of the spine.