CircPRMT5 promotes progression of osteosarcoma by recruiting CNBP to regulate the translation and stability of CDK6 mRNA.

Research has demonstrated that circular RNAs (circRNAs) exert critical functions in the occurrence and progression of numerous malignant tumors. CircPRMT5 was recently reported to be involved in the pathogenesis of cancers. However, the potential role of circPRMT5 in osteosarcoma needs further investigation. In present study, our results suggested that circPRMT5 was highly upregulated in osteosarcoma cells and mainly localizes in the cytoplasm. CircPRMT5 promoted the proliferation, migration and invasion capacities of osteosarcoma cells, and suppressed cell apoptosis. Knockdown of circPRMT5 exerted the opposite effects. Mechanically, circPRMT5 promoted the binding of CNBP to CDK6 mRNA, which enhanced the stability of CDK6 mRNA and facilitated its translation, thereby promoting the progression of osteosarcoma. Knockdown of CDK6 reversed the promoting effect of circPRMT5 on osteosarcoma cells. These findings suggest that circPRMT5 promotes osteosarcoma cell malignant activity by recruiting CNBP to regulate the translation and stability of CDK6 mRNA. Thus, circPRMT5 may represent a promising therapeutic target for osteosarcoma.

[Intestinal absorption components and absorption characteristics of Wuwei Qingzhuo San by everted intestinal sac models].

This study investigated the absorption profile of Wuwei Qingzhuo San in different intestinal segments and the absorption characteristics of its alkaloids(piperine, piperanine, piperlonguminine, and dihydropiperlonguminine). The everted gut sac model was established, and the chemical components of Wuwei Qingzhuo San in different intestinal segments were detected by UPLC-Q-TOF-MS. The content of piperine, piperanine, piperlonguminine, and dihydropiperlonguminine in intestinal absorption fluid was determined by UPLC-Q-TRAP-MS and the absorption parameters were calculated. The absorption characteristics in different intestinal segments at different time were analyzed. As a result, 27, 27, 8, and 6 absorbent components from Wuwei Qingzhuo San were detected in the intestinal cyst fluid of jejunum, ileum, duodenum, and colon by UPLC-Q-TOF-MS technology, respectively. It was also found that piperine, piperanine, piperlonguminine, and dihydropiperlonguminine from Wuwei Qingzhuo San showed linear absorption in various intestinal segments, with r values exceeding 0.9. In terms of absorption content, the components were ranked as piperine>piperanine>dihydropiperlonguminine>piperlonguminine in various intestinal segments, but the absorption rate and mechanism of each component varied. The results demonstrate that the absorption of the components of Wuwei Qingzhuo San in different intestinal segments is selective and is not a simple semi-permeable membrane permeation process.

Efficacy and safety of anisodine hydrobromide injection for acute ischemic stroke: a systematic review and meta-analysis.

Background: Acute ischemic stroke (AIS) is a leading cause of death and disability worldwide. This study aimed to evaluate the efficacy and safety of anisodine hydrobromide (Ani) injection in the treatment of AIS. Methods: Randomized controlled trials (RCTs) based on Ani injection for the treatment of AIS were retrieved from both Chinese and English databases. The retrieval period was from the databases' inception to May 2023. The Cochrane Collaboration Risk of Bias Tool was used to assess the methodological quality. The outcome indicators were analyzed using RevMan 5.3 software. Results: We included the findings of 11 RCTs encompassing 1,337 patients with AIS. Our meta-analysis revealed that Ani injection supplementation significantly reduced the National Institutes of Health Stroke Scale [MD = -1.53, 95%CI = (-1.94, -1.12), p < 0.00001], modified Rankin Scale [MD = -0.89, 95%CI = (-0.97, -0.81), p < 0.00001], and the relative time to peak [SMD = -0.81, 95%CI = (-1.08, -0.55), p < 0.00001] significantly. Additionally, Ani injection significantly increased the Barthel Index [MD = 10.65, 95%CI = (4.30, 17.00), p = 0.001], relative cerebral blood volume [SMD = 0.28, 95%CI = (0.02, 0.53), p = 0.03], and clinical efficacy [RR = 1.2, 95%CI = (1.08, 1.34), p = 0.001]. No statistically significant difference in the rate of adverse events was observed between the Ani injection supplemental group and the control group. Conclusion: Based on currently published evidence, Ani injection was found to be effective and safe in improving AIS outcome. Nevertheless, limitations of the included RCTs still exist, and thus, more multi-center, large-sample, high-quality RCTs are required to further verify the efficacy and safety of Ani injection in patients with AIS. Systematic Review Registration: [https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42023427591], identifier [PROSPERO 2023 CRD42023427591].

The Critical Role of The Piezo1/ß-catenin/ATF4 Axis on The Stemness of Gli1+ BMSCs During Simulated Microgravity-Induced Bone Loss.

Disuse osteoporosis is characterized by decreased bone mass caused by abnormal mechanical stimulation of bone. Piezo1 is a major mechanosensitive ion channel in bone homeostasis. However, whether intervening in the action of Piezo1 can rescue disuse osteoporosis remains unresolved. In this study, a commonly-used hindlimb-unloading model is employed to simulate microgravity. By single-cell RNA sequencing, bone marrow-derived mesenchymal stem cells (BMSCs) are the most downregulated cell cluster, and coincidentally, Piezo1 expression is mostly enriched in those cells, and is substantially downregulated by unloading. Importantly, activation of Piezo1 by systemically-introducing yoda1 mimics the effects of mechanical stimulation and thus ameliorates bone loss under simulated microgravity. Mechanistically, Piezo1 activation promotes the proliferation and osteogenic differentiation of Gli1+ BMSCs by activating the ß-catenin and its target gene activating transcription factor 4 (ATF4). Inhibiting ß-catenin expression substantially attenuates the effect of yoda1 on bone loss, possibly due to inhibited proliferation and osteogenic differentiation capability of Gli1+ BMSCs mediated by ATF4. Lastly, Piezo1 activation also slightly alleviates the osteoporosis of OVX and aged mice. In conclusion, impaired function of Piezo1 in BMSCs leads to insufficient bone formation especially caused by abnormal mechanical stimuli, and is thus a potential therapeutic target for osteoporosis.

Postoperative management of FIGO 2018 stage IIA1 cervical squamous cell carcinoma with only one intermediate-risk factor: Is radiotherapy needed?

OBJECTIVE: To investigate whether postoperative radiotherapy is required for FIGO 2018 stage IIA1 cervical squamous cell carcinoma patients with only one intermediate-risk factor. METHODS: This was a multicenter retrospective study. The selected patients were classified into no postoperative adjuvant therapy and postoperative radiotherapy groups. The 5-year overall survival (OS) and disease-free survival (DFS) rates were compared. RESULTS: In total, 159 patients with no postoperative adjuvant therapy and 179 patients with postoperative radiotherapy were included, with the former group showing a lower OS but no difference in DFS. No postoperative adjuvant therapy was an independent risk factor for patient mortality. Patients were also stratified by tumor diameter: 56 patients had a tumor diameter ≤2 cm, comprising 32 patients with postoperative radiotherapy and 24 patients without (no between-group difference was found); 272 patients had a tumor diameter >2 cm, comprising 122 patients with postoperative radiotherapy and 150 patients without, with the former group showing a higher OS, and no postoperative adjuvant therapy was an independent risk factor for patient mortality. CONCLUSION: For FIGO 2018 stage IIA1 cervical squamous cell carcinoma patients with only one intermediate-risk factor and a tumor diameter >2 cm, postoperative radiotherapy is likely beneficial to improve prognosis.

Comparison of the Perineal Body Between Chinese Women With Pelvic Organ Prolapse and Women With Normal Support by Magnetic Resonance Imaging With 3-Dimensional Reconstruction.

OBJECTIVE: This study aimed to determine whether the perineal body (PB) is different between women with and without prolapse and to analyze its association with prolapse. METHODS: This cross-sectional observational study was performed in a tertiary-level urology department and included patients with stage II-IV pelvic organ prolapse (POP) and normal controls with all points 1 cm or more above the hymen. The patients underwent supine midsagittal magnetic resonance imaging (MRI) at rest and during the maximum Valsalva maneuver. Perineal mobility and PB length, height, perimeter, and area were measured; in addition, the genital hiatus and PB were measured according to the definition of the Pelvic Organ Prolapse Quantification system. Univariate associations of POP with characteristics were assessed using the chi-square test or Fisher exact test for categorical variables and the t test for continuous variables. Multivariate logistic regression analysis was used to estimate the adjusted odds ratios and 95% confidence intervals. RESULTS: Seventy-two controls and 130 patients were analyzed. The PB length, height, and area measurements were significantly lower in the POP group. The perineal mobility in different directions was significantly higher in the POP group. Multivariate analysis demonstrated that the PB area and perineal mobility in the ventral-dorsal and cranio-caudal directions were associated with POP. CONCLUSIONS: Our data suggest that a smaller PB area and greater dorsal or caudal mobility are associated with prolapse.

Three-dimensional magnetic resonance imaging assessment of levator ani in women progressing from full-term pregnancy to 10 months postpartum.

AIM: To identify the anatomical morphology of levator ani (LA) in primigravidae at term pregnancy and its natural process of changing after delivery. METHODS: Forty-one primigravidae (vaginal delivery: 29 women, cesarean delivery in the first stage of labor: 12 women) underwent magnetic resonance imaging (MRI) at full-term pregnancy, 6 weeks and 10 months postpartum. Three-dimensional (3-D) model of LA created from MRI data using Mimics v.21.0 software and source images were assessed to determine the morphology. LA volume (LVOL) was calculated and used as indicator of muscle atrophy. RESULTS: Decrease of levator hiatus length (LH-L) was shown in both groups since 6 weeks postpartum. In the vaginal delivery group, the differences in LVOL between time points were significant (p < 0.05), showing a persistent decreasing tendency. Puborectalis attachment width (PAW) on the left was the smallest at 6 weeks postpartum (p < 0.05). LA avulsion and significant 2-D morphological change after delivery were only observed in this group (p < 0.05); In the cesarean section group, smaller LVOL was found at 6 weeks postpartum comparing with full-term pregnancy (p < 0.05); Larger levator-symphysis gap (LSG) and levator hiatus width (LH-W), smaller PAW were observed in vaginal delivery group comparing with cesarean section group at 6 weeks postpartum (p < 0.05), but none of the values exhibited between-group differences (p > 0.05) at 10 months postpartum. No other comparisons were considered significant (p >0.05). CONCLUSIONS: Vaginal delivery, or even active labor itself may both lead to LA atrophy. And the morphology of LA is basically similar in different delivery modes at 10 months postpartum once the onset of labor has occurred, even though it changes more complicatedly after vaginal delivery.

Mechanosensitive Piezo1 is crucial for periosteal stem cell-mediated fracture healing.

The biomechanical environment plays a dominant role in fracture healing, and Piezo1 is regarded as a major mechanosensor in bone homeostasis. However, the role of Piezo1 in fracture healing is not yet well characterized. In this study, we first delineated that Piezo1 is highly expressed in periosteal stem cells (PSCs) and their derived osteoblastic lineage cells and chondrocytes. Furthermore, downregulation of Piezo1 in callus leads to impaired fracture healing, while activation by its specific agonist promotes fracture healing through stimulation of PSC-modulated chondrogenesis and osteogenesis, along with accelerated cartilage-to-bone transformation. Interestingly, vascular endothelial growth factor A is upregulated after Yoda1 treatment of PSCs, indicating an indirect role of Piezo1 in angiogenesis. Mechanistically, activation of Piezo1 promotes expression of Yes-associated protein (YAP) and its nuclear localization in PSCs, which in turn increases the expression and nuclear localization of ß-catenin. In detail, YAP directly interacts with ß-catenin in the nucleus and forms a transcriptional YAP/ß-catenin complex, which upregulates osteogenic, chondrogenic and angiogenic factors. Lastly, Yoda1 treatment significantly improves fracture healing in a delayed union mouse model generated by tail suspension. These findings indicate that Piezo1 is a potential therapeutic target for fracture delayed union or nonunion.

Genus Spatholobus: a comprehensive review on ethnopharmacology, phytochemistry, pharmacology, and toxicology.

Edible medicinal plants are important sources for the development of health beneficial products and drugs. Several species of the genus Spatholobus are considered as medicinal and food homologous plants in various Asian countries for the treatment of menstrual pain, anemia, paralysis, arthralgia, etc. Regarding this genus, mounting investigations on different aspects have been conducted; however, a comprehensive review about these findings is yet to be compiled. Herein, we reviewed the up-to-date information on the botanical description, distribution, ethnopharmacology, phytochemistry, pharmacology, and toxicology of the Spatholobus species for the first time to support their development potential. Thus far, 175 phytochemicals have been isolated, and flavonoids are the predominant constituents. Furthermore, 141 compounds show the ideal characteristic behavior of a drug-like molecule. Besides, the compounds and crude extracts of this genus have been demonstrated to exert a wide range of in vitro and in vivo bioactivities, such as antitumor activity, antioxidant activity, antiinflammatory activity, antiischemic activity, antimicrobial activity, and neuroprotective activity. Toxicity studies have revealed that Spatholobus species seem to have no apparent toxic effects. Even so, the need for in-depth studies to reveal the scientific connotation of the widely documented traditional actions, the structure-activity relationship of the bioactive compounds, and the systematic toxic reactions are warranted, and also to provide essential evidence for the beneficial use of Spatholobus plants and developing novel health care products and therapeutic drug from this genus.

Country-Brand Fit: The Effect of COO Stereotypes and Brand Positioning Consistency on Consumer Behavior: Evidence From EEG Theta-Band Oscillation.

Grounded on the cognitive consistency theory, this paper adopts the prime-probe paradigm and Electroencephalography (EEG) experiment to examine the impact of country-of-origin (COO) stereotypes-brand positioning congruence on consumer behavior, the boundary effect of brand positioning strategy, as well as the underlying cognitive mechanism. Behaviorally, consumers show a higher purchase intention in the congruence condition. Moreover, this congruence effect of purchase intention can be found for competence brand positioning strategies rather than warmth brand positioning strategies. At the brain level, we found that compared with the congruence condition, the incongruence condition enhances consumers' cognitive conflict, reflected in enhanced frontal theta-band oscillation. Furthermore, the cognitive conflict effect is accentuated in the competence positioning strategy condition rather than the warmth strategy positioning condition, confirming the boundary effect of brand positioning strategy from the brain level. These findings provide neural evidence that the congruence between COO stereotypes and brand positioning influences consumer purchase behavior, reveals a boundary effect in the COO stereotype-brand positioning congruence, and highlights the importance of the competence dimension. Finally, the theoretical and practical implications are discussed.

Wnt10b-overexpressing umbilical cord mesenchymal stem cells promote fracture healing via accelerated cartilage callus to bone remodeling.

The aim of this study was to investigate whether HUCMSCsWnt10b could promote long bone fracture healing. Commercially-available HUCMSCsEmp (human umbilical cord mesenchymal stem cells transfected with empty vector) in hydrogel, HUCMSCsWnt10b in hydrogel and HUCMSCsWnt10b with the Wnt signaling pathway inhibitor IWR-1 were transplanted into the fracture site in a rat model of femoral fracture. We found that transplantation of HUCMSCsWnt10b significantly accelerated bone healing in a rat model of femoral fracture. Meanwhile, three-point bending test proved that the mechanical properties of the bone at the fracture site in the HUCMSCWnt10b treatment group were significantly better than those of the other treatment groups. To understand the cellular mechanism, we explored the viability of periosteal stem cells (PSCs), as they contribute the greatest number of osteoblast lineage cells to the callus. In line with in vivo data, we found that conditioned medium from HUCMSCsWnt10b enhanced the migration and osteogenic differentiation of PSCs. Furthermore, conditioned medium from HUCMSCsWnt10b also induced endothelial cells to form capillary-like structures in a tube formation assay, which was blocked by SU5416, an angiogenesis inhibitor, suggesting that enhanced vessel formation and growth also contribute to accelerated hard callus formation. In summary, our study demonstrates that HUCMSCsWnt10b promote fracture healing via accelerated hard callus formation, possibly due to enhanced osteogenic differentiation of PSCs and vessel growth. Therefore, HUCMSCsWnt10b may be a promising treatment for long bone fractures.

KLF9 regulates miR-338-3p/NRCAM axis to block the progression of osteosarcoma cells.

Background: MiR-338-3p is revealed to serve as a tumor suppressor in several carcinomas. Whereas, the effect of miR-338-3p in the progression of osteosarcoma has not been explored. The aim of this paper was to analyze the functional influences of miR-338-3p on osteosarcoma progression and the potential mechanism. Methods: The expression of genes and miRNAs in osteosarcoma cells was assessed via western blotting or quantitative reverse transcription-polymerase chain reaction (qRT-PCR). Osteosarcoma cellular proliferation was explored by MTT and EdU incorporation assay. Osteosarcoma cellular migratory and invasive capacity was explored by wound-healing and transwell assay. Bioinformatics approaches were adopted to predict target genes. The relationships between miR-338-3p and neuron­glial­related cell adhesion (NRCAM), between kruppel-like factor 9 (KLF9) and miR-338-3p were verified by dual-luciferase reporter assay. Results: We found that miR-338-3p was reduced in osteosarcoma and that higher expression of miR-338-3p suppressed proliferative, invasive and migratory ability of osteosarcoma cells. Furthermore, the result showed that overexpression of NRCAM could reduce the anti-tumor role of miR-338-3p in osteosarcoma cells. In addition, we found that overexpression of KLF9 could enhance the expression level of miR-338-3p in osteosarcoma cells. Conclusion: The KLF9/miR-338-3p/NRCAM axis played a significant role in regulating osteosarcoma progression, which may become a promising therapeutic method for osteosarcoma.

Effect of Preeclampsia on Ultrastructure of Thyroid Gland, Hepatic Type 1 Iodothyronine Deiodinase, and Thyroid Hormone Levels in Rats.

BACKGROUND: Although hypothyroidism during pregnancy may develop grave outcomes for both mothers and offspring, management of which is still a challenge due to the insufficient understanding of this disease. The close correlation between hypothyroidism and preeclampsia is well documented, suggesting that preeclampsia is a potential risk factor for the development of maternal hypothyroidism. However, the exact role of preeclampsia in gestational hypothyroidism is still obscure. OBJECTIVE: In this study, we explored the possible mechanisms of the effect of preeclampsia on thyroid function of maternal rats. METHODS: Thirty pregnant rats were randomly divided into normal pregnancy control (NOP), preeclampsia (PE), and preeclampsia supplemented with amlodipine besylate (PEAml). NG-Nitro-L-arginine-methyl ester was used to induce preeclamptic symptoms. On gestational day 21, rats were sacrificed, and then, the ultrastructure of the thyroid gland, type 1 iodothyronine deiodinase (Dio1) expression, and serum-free thyroxine (FT4), free triiodothyronine (FT3), and thyroid stimulation hormones (TSH) were assessed. RESULTS: Compared to NOP rats, results of PE rats showed that thyroid follicular cells' ultrastructure was damaged; both hepatic Dio1 mRNA and protein levels were decreased. Interestingly, these changes were ameliorated in PEAml rats. Additionally, FT4, FT3, and TSH levels have no significant differences among groups. CONCLUSION: These findings indicated that preeclampsia could disrupt synthesis, secretion, and metabolism function of thyroid hormones by damaging thyroid follicular cells and interfering Dio1 expression.

Corrigendum: Protecting Healthcare Workers Amid the COVID-19 Crisis: A Safety Protocol in Wuhan.

[This corrects the article DOI: 10.3389/fpubh.2020.577499.].

Ischemic Necrosis of Lower Extremity in COVID-19: A Case Report.

Coronavirus disease 2019 (COVID-19), which is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is an acute infectious disease that spreads mainly via the respiratory route. Elderly patients or those with underlying diseases are more seriously affected. We report a case of COVID-19 infection in a geriatric patient with arteriovenous thrombosis of the right lower limb. Despite persistent anticoagulant therapy, the patient's arterial thrombosis continued to progress and presented with ischemic necrosis of the lower extremity. After amputation in this case, the levels of D-dimer and inflammatory cytokine increased progressively, and he presented with acute myocardial infarction, which progressed rapidly to multisystem organ failure. However, whether coronavirus can directly cause the damage of the cardiovascular system and thrombosis needs further investigation.

Protecting Healthcare Workers Amid the COVID-19 Crisis: A Safety Protocol in Wuhan.

Coronavirus disease 2019 (COVID-19), which is caused by a distinct coronavirus, is an acute infectious disease that spreads mainly via the respiratory route. During the COVID-19 outbreak, many healthcare systems faced a severe burden when a large number of healthcare workers (HCWs) became infected due to the lack of adequate protection. Consequently, it was apparent that it is important to ensure the health and safety of HCWs in order to control the outbreak throughout society. In this article, we share our successful protocol for protecting the safety of HCWs in the course of their daily work in an orthopedics department with the aim of eventually reducing the risk of nosocomial infection. None of our HCWs or their families contracted the infection during the COVID-19 pandemic.

Effects of Anisodine Hydrobromide on the Cardiovascular and Respiratory Functions in Conscious Dogs.

PURPOSE: Anisodine hydrobromide (Ani) is isolated from the medicinal plant Anisodus tanguticus (Maxim.) Pascher for clinical use. Although considerable research regarding Ani has been reported, the safety profiles of Ani are currently unknown. This study investigated the cardiorespiratory effects of Ani in conscious dogs to provide clinicians a detailed safety profile of Ani on the cardiorespiratory system. MATERIALS AND METHODS: Using the Latin square design, the study was divided into six phases, where in each phase, six telemetered beagle dogs received one dose of normal saline or sotalol hydrochloride or Ani (0.1, 0.4, 1.6, or 6.4 mg/kg). Electrocardiogram, blood pressure (BP) and respiratory parameters were collected before and after administration for 24 hours. Statistical comparisons were performed at scheduled time-points. RESULTS: The heart rate was significantly increased, PR and QTCV intervals were significantly shortened in Ani 0.4, 1.6, 6.4 mg/kg treatment group after drug administration. Compared with the saline group, a significant increase in heart rate and shortening of PR, QTCV intervals were observed in the Ani 1.6, 6.4 mg/kg treatment groups from 5 min to 4 h time-points. Diastolic and mean BP were significantly increased in Ani 1.6, 6.4 mg/kg from 1 h to 2 h time-points compared to those of the saline control. Accelerated breathing was observed in the first 20 min after Ani 0.4, 1.6, and 6.4 mg/kg treatment, although not statistically significant. Furthermore, no significant differences were observed in any of the corresponding indexes of Ani 0.1 mg/kg treatment group at different time-points compared to those of the saline group. CONCLUSION: Ani may have adverse effects on the cardio-respiratory systems of dogs at doses above 0.4 mg/kg, whereas Ani 0.1 mg/kg was devoid of potentially deleterious effects on cardiorespiratory function.

A network meta-analysis protocol of conservative interventions for urinary incontinence in postpartum women.

BACKGROUND: Postpartum urinary incontinence (PPUI) is a common urological condition in women after childbirth. Due to the side effects of surgical and pharmacological therapies, the patients and physicians alike express a strong preference for conservative approaches on PPUI, such as pelvic floor muscle training, biofeedback, electrical stimulation, bladder training, vaginal cones and acupuncture. Application of these conservative approaches should be guided by high quality evidence, yet their comparative effectiveness has not been well documented. Therefore, the network meta-analysis aims to compare, rank and summarize all available studies to determine which conservative intervention is more effective for PPUI. METHODS: In this present study, qualified English and Chinese studies will be searched in PubMed, Scopus, EMBASE, The Cochrane Library, Web of Science, VIP Database, Wanfang Database, Chinese Biomedical Literature Database and China National Knowledge Infrastructure. All eligible randomized controlled trails (RCTs) of conservative interventions for PPUI will be included. R software 3.61 (R Foundation for Statistical Computing, Vienna, Austria) will be applied to synthesize data and conduct network meta-analysis. I statistic and Z test will be used to assess heterogeneity and inconsistency, respectively. RESULTS: Ethical approval is not required for this existed literature based meta-analysis. The findings of this research will be disseminated through a recognized journal. CONCLUSION: The findings of this study will provide ranking evidence for clinicians and patients to choose a more appropriate conservative therapy on PPUI. TRIAL REGISTRATION NUMBER: PROSPERO CRD42020168042.

Non-pharmacological interventions for postpartum depression: A protocol for systematic review and network meta-analysis.

BACKGROUND: Postpartum depression (PPD) is one of the most common mental disorders in women following childbirth with heightened prevalence across the globe. Both pharmacotherapy and non-pharmacological interventions are effective for PPD. However, due to the concerns about the side effect on the mother and child of pharmacological treatments, most of women with PPD choose non-pharmacological therapies as their first line option. Prescription of these non-drug approaches should be guided by high quality evidence. Therefore, this network meta-analysis aims to compare, rank and interpret existed non-pharmacological evidence for the effective treatment of women with PPD. METHODS: Electronic bibliographic databases including EMBASE, PubMed, Scopus, The Cochrane Library, Web of Science, China National Knowledge Infrastructure (CNKI),VIP Database, Wanfang Database and Chinese Biomedical Literature Database will be searched for relevant randomized controlled trials (RCTs) of non-pharmacological interventions for PPD. Heterogeneity and inconsistencies will be analyzed by I statistic and Z test, respectively. We will assess the quality of evidence by the Grading of Recommendations Assessment, Development and Evaluation (GRADE) and evaluate the risk of bias according to Cochrane risk of bias tool. R software 3.6.1 (R Foundation for Statistical Computing, Vienna, Austria) will be used to conduct a network meta-analysis. RESULTS: Formal ethical approval is not required, because the present study is a meta-analysis based on existed studies. The findings of this research will be reported in a recognized journal. CONCLUSION: The review results will ascertain the hierarchy of effectiveness of different non-pharmacological approaches for PPD, and systematically provide suggests for physicians and patients. TRIAL REGISTRATION NUMBER: PROSPERO CRD42020166801.

Pioglitazone Protects Compression-Mediated Apoptosis in Nucleus Pulposus Mesenchymal Stem Cells by Suppressing Oxidative Stress.

Excessive compression, the main cause of intervertebral disc (IVD) degeneration, affected endogenous repair of the intervertebral disc. Pioglitazone (PGZ) is the agonist of peroxisome proliferator-activated receptor γ, which has been widely used in the treatment of diabetes mellitus. The present study aim at investigating whether pioglitazone has protective effects on compression-mediated cell apoptosis in nucleus pulposus mesenchymal stem cells (NP-MSCs) and further exploring the possible underlying mechanism. Our results indicated that the isolated cells satisfied the criteria of MSC stated by the International Society for Cellular Therapy. Besides, our research revealed that pioglitazone could protect cell viability, cell proliferation of NP-MSCs and alleviated the toxic effects caused by compression. The actin stress fibers was suppressed obviously under compression, and pioglitazone alleviated the adverse outcomes. Pioglitazone exerted protective effects on compression-induced NP-MSCs apoptosis according to annexin V/PI double-staining and TUNEL assays. Pioglitazone suppressed compression-induced NP-MSCs oxidative stress, including decreasing compression-induced overproduction of reactive oxygen species (ROS) and malondialdehyde (MDA), and alleviated compression-induced mitochondrial membrane potential (MMP) decrease. Ultrastructure collapse of the mitochondria exhibited a notable improvement by pioglitazone in compression-induced NP-MSCs according to transmission electron microscopy (TEM). Furthermore, the molecular results showed that pioglitazone significantly decreased the expression of apoptosis-associated proteins, including cyto.cytochrome c, Bax, cleaved caspase-9, and cleaved caspase-3, and promoted Bcl-2 expression. These results indicated that pioglitazone alleviated compression-induced NP-MSCs apoptosis by suppressing oxidative stress and the mitochondrial apoptosis pathway, which may be a valuable candidate for the treatment of IVD degeneration.