Efficacy and safety of Xiaoyao Pill combined with Western medicine in the treatment of schizophrenia: A Meta-analysis and Systematic review.

BACKGROUND: The efficacy and safety of Xiaoyao Pill combined with Western medicine in the treatment of schizophrenia are still inconclusive. This meta-analysis summarized relevant studies to compare the efficacy and safety of Xiaoyao Pill combined with Western medicine and Western medicine alone in the treatment of schizophrenia, aiming to provide guidance for clinical treatment. METHODS: In this meta-analysis, we searched PubMed, Embase, Cochrane Library, CNKI, Wanfang, CQVIP, and CBM databases from the establishment of the databases to August 2023. The study proposed to include studies that reported combination of Xiaoyao Pill with Western medicine and Western medicine alone in the treatment of schizophrenia, excluding published literature, unpublished literature, literature with incomplete or inadequate information, animal experiments, literature reviews and systematic studies. Data were analyzed using Review manager 5.3. RESULTS: About 9 studies (6 RCTs and 3 case-control studies) were included in this meta-analysis. The sample size ranged from 60 to 128, with a total of 779 patients, including 395 in the combined treatment group and 384 in the control group. Pooled results showed that the total effective rate of combined treatment group was significantly higher than that of Western medicine alone (OR = 4.21, 95% CI: 1.50-11.83, P = .006). Positive and Negative Syndrome Scale (PANSS) (-) (MD = -2.30, 95% CI: -3.72 ~ -0.89, P = .001) and PANSS (+) (MD = -2.60, 95% CI: -3.34 ~ -1.86, P < .00001) of combined treatment group were all significantly lower than that of Western medicine alone. Additionally, PRL levels of combined treatment group was significantly lower than that of Western medicine alone (MD = -28.78, 95% CI: -42.20 ~ -15.35, P < .0001). However, there was no significant difference in BPRS and total PANSS between combined treatment group and Western medicine alone group. Notably, pooled results showed that there was no significant difference in incidence of adverse events between combined treatment group and Western medicine alone group. CONCLUSION: The effective rate of Xiaoyao Pill combined with Western medicine in the treatment of schizophrenia is higher than that of Western medicine alone, which can effectively relieve the positive and negative symptoms of schizophrenia, and can significantly reduce the level of PRL. In the treatment of schizophrenia, clinicians can give priority to Xiaoyao Pill combined with Western medicine therapy.

Investigating the Potential Mechanisms and Therapeutic Targets of Inflammatory Cytokines in Post-stroke Depression.

Post-stroke depression (PSD) affects approximately one-third of stroke survivors, severely impacting general recovery and quality of life. Despite extensive studies, the exact mechanisms underlying PSD remain elusive. However, emerging evidence implicates proinflammatory cytokines, including interleukin-1ß, interleukin-6, tumor necrosis factor-alpha, and interleukin-18, play critical roles in PSD development. These cytokines contribute to PSD through various mechanisms, including hypothalamic-pituitary-adrenal (HPA) axis dysfunction, neurotransmitter alterations, neurotrophic factor changes, gut microbiota imbalances, and genetic predispositions. This review is aimed at exploring the role of cytokines in stroke and PSD while identifying their potential as specific therapeutic targets for managing PSD. A more profound understanding of the mechanisms regulating inflammatory cytokine expression and anti-inflammatory cytokines like interleukin-10 in PSD may facilitate the development of innovative interventions to improve outcomes for stroke survivors experiencing depression.

Complete perforated bladder from intrauterine devices: A case series report from a nationwide monitoring system.

AIM: Complete perforation of the bladder caused by an intrauterine device (IUD) is rare. This study examined the characteristics of patients associated with IUD-related bladder perforation and evaluated the relationship between mislocated IUDs and their potential complications. METHODS: From October 2005 to December 2021, 13 reports regarding complete perforations to the bladder by IUDs were retrieved from the National Contraceptives Adverse Reaction Monitoring System of China. The clinical features of these cases were analyzed. RESULTS: The median patient age was 30 (range, 27-46) years. There were four cases (4/13, 30.8%) with IUDs placed during lactation, one case (1/13, 7.7%) with an IUD placed after medical abortion, and eight cases (8/13, 61.5%) placed after menstruation. Seven cases (7/13, 53.9%) were first-time IUD users. The median duration of IUD placement was 47 (range, 1-145) months. Unexpected pregnancy was reported in five cases (5/13, 38.5%). Six cases (6/13, 46.2%) reported bladder stones with varying degrees of abdominal pain or urinary tract infection. Removal methods included laparotomy (four cases), cystoscopy (four cases), laparoscopy (two cases), laparoscopy combined with cystoscopy (two cases), and laparotomy after cystoscopy (one case). All IUDs were successfully removed. CONCLUSIONS: Complete perforation to the bladder by IUDs is a rare adverse event. Regular follow-up is required after the placement of IUDs. The possibility of uterine perforation should be investigated if IUD users encounter persistent lower abdominal pain or urinary tract infection.

Spontaneous symmetry-breaking of the active cluster drives the directed movement and self-sustained oscillation of symmetric rod-like passive particles.

Active particles without detailed balance can rectify their random motions to drive the directed movement or rotation of asymmetric passive obstacles. However, whether they can drive the directed movement of symmetric passive obstacles is still unclear. Here, we show that a rod-like passive particle which is fixed to move along the x-axis in an active bath can keep long-lived directed movement at nearly constant speed due to the spontaneous symmetry breaking of the neighboring active particle cluster. If the passive particle is further confined by a harmonic potential, it may undergo self-sustained periodic oscillation for an appropriate length of the passive particle and self-propelled velocity of active particles. The restoring force from the harmonic potential will trigger the velocity jump-off and thus lead to self-sustained periodic oscillation. Remarkably, the relationship between the velocity of the passive particle and the external force shows that the effective viscosity of the active bath may become negative in some regime. Finally, we develop a minimum 1D theoretical model to further probe the mechanism underlying the directed movement and self-sustained oscillation of the passive particle. Our findings reveal the effect of the moving boundary on the active bath and demonstrate a novel method to extract practical mechanical work from the active bath to propel microdevices.

Lateral locking plate plus antero-posterior lag screws techniques for the management of posterolateral tibial plateau fracture: preliminary clinical results and biomechanical study.

INTRODUCTION: To date, there is no consensus on the optimal surgical strategy for the treatment of posterolateral tibial plateau fracture (PLF). This study introduced a novel, simple technique for treating PLF with a lateral locking plate plus antero-posterior lag screws (LPpLS). METHODS: We conducted a retrospective case series of 42 patients (Female/Male 19/23) with PLF treated with LPpLS between 1 July 2016 and 30 June 2019. Several pre- and postoperative outcomes were recorded, including operative time, intraoperative blood loss, CT findings, HSS, and ROM. For biomechanical studies, seventy synthetic tibiae with a simulated posterolateral split fracture were divided into seven groups. The biomechanical evaluation included displacement measurement at axial compression and fatigue testing. RESULTS: Forty-two eligible patients were followed up for an average of 18 months (range 14-21 months). Postoperative radiographs and CT showed good positioning of plates and screws, no fracture fragment loss, and normal articular surfaces in all 42 cases. The biomechanical study showed that the axial stiffness of LPpLS was in the same fashion as the posterior buttress plate and better than the other fixation methods (P < 0.05). Additionally, the LPpLS group had a smaller displacement of fracture fragments along the X-axis (medial to lateral direction) than the BP group (P < 0.01). CONCLUSIONS: The LPpLS technique could implement good reconstruction of the PLF, showing satisfactory therapeutic effect. The biomechanical evaluation demonstrated that the LPpLS had better stability in three-dimensional directions for PLF than other fixation strategies.

A Low Dose of Ouabain Alters the Metabolic Profile of Adult Rats Experiencing Intrauterine Growth Restriction in a Sex-Specific Manner.

Intrauterine growth restriction (IUGR) increases the risk of type 2 diabetes mellitus (T2DM) and metabolic diseases. The pancreas of fetuses with IUGR is usually characterized by pancreatic dysplasia and reduced levels of insulin secretion caused by the diminished replication of ß-cells. Previous studies showed that a low dose of ouabain could reduce the apoptosis of embryonic nephric cells during IUGR and partially restore the number of nephrons at birth. The rescued kidneys functioned well and decreased the prevalence of hypertension. Thus, we hypothesized that ouabain could rescue pancreatic development during IUGR and reduce the morbidity of T2DM and metabolic diseases. Maternal malnutrition was used to induce the IUGR model, and then a low dose of ouabain was administered to rats with IUGR during pregnancy. Throughout the experiment, we monitored the pattern of weight increase and evaluated the metabolic parameters in the offspring in different stages. Male, but not female, offspring in the IUGR group presented catch-up growth. Ouabain could benefit the impaired glucose tolerance of male offspring; however, this desirable effect was eliminated by aging. The insulin sensitivity was significantly impaired in male offspring with IUGR, but it was improved by ouabain, even during old age. However, in the female offspring, low birth weight appeared to be a beneficial factor even in old age; administering ouabain exacerbated these favorable effects. Our data suggested that IUGR influenced glucose metabolism in a sex-specific manner and ouabain treatment during pregnancy exerted strongly contrasting effects in male and female rats.

Electromechanical model for object roughness perception during finger sliding.

Touch allows us to gather abundant information in the world around us. However, how sensory cells embedded in the fingers convey texture information into their firing patterns is still poorly understood. Here, we develop an electromechanical model for roughness perception by incorporating main ingredients such as voltage-gated ion channels, active ion pumps, mechanosensitive channels, and cell deformation. The model reveals that sensory cells can convey texture wavelengths into the period of their firing patterns as the finger slides across object surfaces, but they can only convey a limited range of texture wavelengths. We also show that an increase in sliding speed broadens the decoding wavelength range at the cost of reduction of lower perception limits. Thus, a smaller sliding speed and a bigger contact force may be needed to successfully discern a smooth surface, consistent with previous psychophysical observations. Moreover, we show that cells with slowly adapting mechanosensitive channels can still fire action potentials under static loadings, indicating that slowly adapting mechanosensitive channels may contribute to the perception of coarse textures under static touch. Our work thus provides a new theoretical framework to study roughness perception and may have important implications for the design of electronic skin, artificial touch, and haptic interfaces.

Bioinspired Nanovesicles Convert the Skeletal Endothelium-Associated Secretory Phenotype to Treat Osteoporosis.

Recently, bone marrow endothelial cells (BMECs) were found to play an important role in regulating bone homeostasis. However, few studies utilized BMECs to treat bone metabolic diseases including osteoporosis. Here, we reported bioinspired nanovesicles (BNVs) prepared from human induced pluripotent stem cells-derived endothelial cells under hypoxia culture through an extrusion approach. Abundant membrane C-X-C motif chemokine receptor 4 conferred these BNVs bone-targeting ability and the endothelial homology facilitated the BMEC tropism. Due to their unique endogenous miRNA cargos, these BNVs re-educated BMECs to secret cytokines favoring osteogenesis and anti-inflammation. Owing to the conversion of secretory phenotype, the osteogenic differentiation of bone mesenchymal stem cells was facilitated, and the M1-macrophage-dominant pro-inflammatory microenvironment was ameliorated in osteoporotic bones. Taken together, this study proposed BMEC-targeting nanovesicles treating osteoporosis via converting the skeletal endothelium-associated secretory phenotype.

A clinical and biomechanical comparison of INFIX plus single versus double sacroiliac screw fixation for unstable pelvic ring injury.

BACKGROUND: The aim of this study is to compare the clinical and biomechanical outcome of INFIX plus single with two sacroiliac screw fixation for unstable pelvic fractures of Type C. METHODS: Sixteen cadavers were randomly subjected to INFIX plus single or double sacroiliac screw fixations and then mounted onto the ElectroForce loading machine under different vertical loads. To investigate the clinical outcomes of the two techniques, nineteen patients were retrospectively analyzed. The main outcome measures were postoperative radiographic reduction grading (using the Tornetta and Matta grading system), functional outcome (using the Majeed scoring system), and incidence of complications. RESULTS: In the biomechanical study, INFIX plus double sacroiliac screw fixation showed better biomechanical stability than fixation with a single sacroiliac screw (p < 0.05). In our clinical case series, all 19 patients had bony union 6 months after the operation. INFIX plus double sacroiliac screw fixation also demonstrated a better functional outcome and a higher radiographic satisfactory rate than INFIX plus single sacroiliac screw fixation (79.25 ± 5.47; 91.33 ± 4.97; p < 0.05), (77.78% vs. 60%; p = 0.05). One patient in INFIX plus single-screw fixation group had screw loosening at 6-month follow-up postoperatively. One case in each group suffered heterotopic ossification and the lateral femoral cutaneous nerve paralysis, and one patient suffered from infection. CONCLUSION: INFIX plus double sacroiliac screw fixation demonstrated more stability in cadaveric biomechanical analysis and better clinical outcomes than INFIX plus single sacroiliac screw fixation.

Intercellular water exchanges trigger soliton-like waves in multicellular systems.

Oscillations and waves are ubiquitous in living cellular systems. Generations of these spatiotemporal patterns are generally attributed to some mechanochemical feedbacks. Here, we treat cells as open systems, i.e., water and ions can pass through the cell membrane passively or actively, and reveal a new origin of wave generation. We show that osmotic shocks above a shock threshold will trigger self-sustained cell oscillations and result in long-range waves propagating without decrement, a phenomenon that is analogous to the excitable medium. The traveling wave propagates along the intercellular osmotic pressure gradient, and its wave speed scales with the magnitude of intercellular water flows. Furthermore, we also find that the traveling wave exhibits several hallmarks of solitary waves. Together, our findings predict a new mechanism of wave generation in living multicellular systems. The ubiquity of intercellular water exchanges implies that this mechanism may be relevant to a broad class of systems.

Recurrent acute portal vein thrombosis with severe abdominal infection after right hemihepatectomy in a patient with perihilar cholangiocarcinoma: A case report and literature review.

INTRODUCTION AND IMPORTANCE: Portal vein thrombosis (PVT) is a serious complication after hepatobiliary-pancreatic surgery. There have been few studies on recurrent PVT after hepatectomy for perihilar cholangiocarcinoma. CASE PRESENTATION: We report the case of a 66-year-old woman who was diagnosed with perihilar cholangiocarcinoma and treated with right hemihepatectomy. On the sixth day, the patient developed acute portal vein thrombosis, and emergency portal vein incision and surgical thrombectomy were performed. On the seventh day after thrombectomy, the patient developed acute portal vein thrombosis again, and portal vein thrombectomy+portal vein bridging was performed again. There was still thrombosis after the operation. The patient was then treated with superior mesenteric arteriography + indirect portal vein catheterization thrombolysis and local thrombolysis + anticoagulation and systemic anticoagulation therapy. The patient had a complicated abdominal infection. The total hospital stay was 84 days. There was no thrombosis in the portal vein at discharge. CLINICAL DISCUSSION: Although the procedure was carefully performed with a preoperative plan and fine intraoperative vascular anastomosis, postoperative PVT occurred. There are many factors of portal vein thrombosis, and there are many treatment methods. CONCLUSION: PVT often develops in patients with liver cirrhosis postoperatively and after liver transplantation. Recurrent PVT after hepatectomy for perihilar cholangiocarcinoma is a rare complication.

Advances in pathogenesis and therapeutic strategies for osteoporosis.

Osteoporosis, is the most common bone disorder worldwide characterized by low bone mineral density, leaving affected bones vulnerable to fracture. Bone homeostasis depends on the precise balance between bone resorption by osteoclasts and bone matrix formation by mesenchymal lineage osteoblasts, and involves a series of complex and highly regulated steps. Bone homeostasis will be disrupted when the speed of bone resorption is faster than bone formation. Based on various regulatory mechanisms of bone homeostasis, a series of drugs targeting osteoporosis have emerged in clinical practice, including bisphosphonates, selective estrogen receptor modulators, calcitonin, molecular-targeted drugs and so on. However, many drugs have major adverse effects or are unsuitable for long-term use. Therefore, it is very urgent to find more effective therapeutic drugs based on the new pathogenesis of osteoporosis. In this review, we summarize novel mechanisms involved in the pathological process of osteoporosis, including the roles of gut microbiome, autophagy, iron balance and cellular senescence. Based on the above pathological mechanism, we found promising drugs for osteoporosis treatment, such as: probiotics, alpha-ketoglutarate, senolytics and hydrogen sulfide. This new finding may provide an important basis for elucidating the complex pathological mechanisms of osteoporosis and provide promising drugs for clinical osteoporosis treatment.

Single-stage debridement via autogenous iliac bone graft through the OLIF corridor and lateral fixation in treating spontaneous single-level lumbar pyogenic spondylodiscitis.

BACKGROUND: The aim of the present study was to investigate the efficacy and safety of mini-open oblique debridement and lumbar interbody fusion combined with lateral screw fixation for treating single-level pyogenic spondylodiscitis. METHODS: Twelve patients with single-level lumbar pyogenic spondylodiscitis underwent OLIF combined with lateral screw fixation were analyzed. Patients underwent follow-up for 12 to 24 months. The clinical characteristics, etiological examinations, operative time, intraoperative blood loss, Oswestry Disability Index (ODI), visual analog scale score (VAS), postoperative complications, and the bony fusion rate were recorded. RESULTS: The mean follow-up period of time was 14.8 months. The average operative time and intra-operative blood loss were 129.0 ± 19.76 min and 309.2 ± 92.96 mL, respectively. No severe intra-operative complications were observed during surgery, except in 1 case that develops abdominal pain and distension after surgery, 2 cases that develop left-sided transient thigh pain/numbness and 8 cases that complains of donor site (iliac crest) pain. All of these symptoms disappeared 8 weeks after surgery. Tissue sample cultures were obtained from all patients intraoperatively and four (33.3%) were positive, including 2 with Staphylococcus aureus, 1 with Staphylococcus epidermidis, and 1 with Escherichia coli. During an average of 22.5 ± 2.1 days (range, 14-29 days) after surgery, WBC, CPR, and ESR levels in all patients had returned to normal. All patients were pain free with no recurring infection. Solid bony fusions were observed in all cases within 6 months, including 10 with I grade fusion, 2 with II grade fusion according to the classification suggested by Burkus et al. No fixation failure was observed during follow up and solid bony fusions were observed in all 12 patients at finally follow-up. A significant postoperative increase was also observed in the mean segmental height and lordosis (P < 0.05), followed by a slight decrease of segmental height and lordosis at final follow-up. At the final follow up, the mean VAS (1.5 ± 0.6) and ODI (18.9 ± 7.6) were significantly lower than VAS (8.4 ± 2.7) and ODI (71.2 ± 16.5) before surgery (P < 0.01). CONCLUSION: Single-stage debridement with autogenous iliac bone graft through the OLIF corridor and lateral fixation was a feasible surgical approach in our consecutive 12 cases of pyogenic spondylitis.

Endocytosis and exocytosis protect cells against severe membrane tension variations.

The ability of cells to regulate their shape and volume is critical for many cell functions. How endocytosis and exocytosis, as important ways of membrane trafficking, affect cellular volume regulation is still unclear. Here, we develop a theoretical framework to study the dynamics of cell volume, endocytosis, and exocytosis in response to osmotic shocks and mechanical loadings. This model can not only explain observed dynamics of endocytosis and exocytosis during osmotic shocks but also predict the dynamics of endocytosis and exocytosis during cell compressions. We find that a hypotonic shock stimulates exocytosis, while a hypertonic shock stimulates endocytosis; and exocytosis in turn allows cells to have a dramatic change in cell volume but a small change in membrane tension during hyposmotic swelling, protecting cells from rupture under high tension. In addition, we find that cell compressions with various loading speeds induce three distinct dynamic modes of endocytosis and exocytosis. Finally, we show that increasing endocytosis and exocytosis rates reduce the changes in cell volume and membrane tension under fast cell compression, whereas they enhance the changes in cell volume and membrane tension under slow cell compression. Together, our findings reveal critical roles of endocytosis and exocytosis in regulating cell volume and membrane tension.

Mechanical properties of external confinement modulate the rounding dynamics of cells.

Many studies have demonstrated that mitotic cells can round up against external impediments. However, how the stiffness of external confinement affects the dynamics of rounding force/pressure and cell volume remains largely unknown. Here, we develop a theoretical framework to study the rounding of adherent cells confined between a substrate and a cantilever. We show that the rounding force and pressure increase exclusively with the effective confinement on the cell, which is related to the cantilever stiffness and the separation between cantilever and substrate. Remarkably, an increase of cantilever stiffness from 0.001 to 1 N/m can lead to a 100-fold change in rounding force. This model also predicts an active role of confinement stiffness in regulating the dynamics of cell volume and hydrostatic pressure. We find that the dynamic changes of cellular volume and hydrostatic pressure after osmotic shocks are opposite if the cantilever is soft, whereas the dynamic changes of cellular volume and pressure are the same if the cantilever is stiff. Taken together, this work demonstrates that confinement stiffness appears as a critical regulator in regulating the dynamics of rounding force and pressure. Our findings also indicate that the difference in cantilever stiffness need to be considered when comparing the measured rounding force and pressure from various experiments.

Oxidative stress induces downregulation of TP53INP2 and suppresses osteogenic differentiation of BMSCs during osteoporosis through the autophagy degradation pathway.

Oxidative stress plays an important role in the pathogenesis of osteoporosis and impaired bone formation. However, the mechanisms behind which oxidative stress represses bone formation remains unclear. TP53INP2, a target of the tumor suppressor p53, is ubiquitously expressed in various cell types including BMSCs and contributes to autophagosome formation by recruiting ubiquitinated substrates to autophagosomes for degradation. However, little is known about its function in BMSCs and its relation to osteoporosis. In this study, first, we verified that the expression of TP53INP2 was persistently decreased in BMSCs derived from osteoporosis patients and OVX mice, and that the antioxidant N-acetylcysteine could ameliorate this decreased TP53INP2 level in vitro. Second, we identified that the mRNA and protein levels of TP53INP2 decreased in BMSCs under H2O2 induced oxidative stress in a dose-dependent manner, with resultant co-location of LC3 and TP53INP2. Additionally, the autophagy-lysosome system was involved in the degradation process of TP53INP2 and applying autophagy inhibitors (Baf-A1) could significantly increase the TP53INP2 levels in murine and human BMSCs under oxidative stress. Third, gain- and loss-of-function assays revealed that knockdown of TP53INP2 inhibited osteogenic differentiation of BMSCs, while overexpression of TP53INP2 promoted osteogenic differentiation of BMSCs in vitro. Further analysis demonstrated that TP53INP2 promoted osteogenic differentiation of BMSCs by activating Wnt/ß-cantenin signaling. DKK1, an inhibitor of Wnt signaling, resulted in osteogenic defects of BMSCs that had over-expressed TP53INP2. Lithium, a Wnt/ß-catenin activator, improved the mineralization ability in TP53INP2-knockdown BMSCs. Moreover, restoring TP53INP2 levels recovered OVX-derived BMSCs osteogenic differentiation and attenuated bone loss in OVX mice. Taken together, our study indicated that oxidative stress-induced downregulation of TP53INP2 suppressed osteogenic differentiation of BMSCs during osteoporosis and was mediated by the autophagy degradation pathway. These findings may introduce a novel therapeutic target for osteoporosis.

Autophagy in spinal ligament fibroblasts: evidence and possible implications for ossification of the posterior longitudinal ligament.

BACKGROUND: The molecular mechanisms of ossification of the posterior longitudinal ligament (OPLL) remain to be elucidated. The aim of the present study was to investigate the autophagy of spinal ligament fibroblasts derived from patients with OPLL and to examine whether autophagy-associated gene expression was correlated with the expression of osteogenic differentiation genes. METHODS: Expression of autophagy-associated genes was detected in 37 samples from 21 OPLL patients and 16 non-OPLL patients. The correlation of autophagy-associated gene expression and the expression of osteogenic differentiation genes was analyzed by Pearson's correlation. The expression of autophagy-associated genes of ligament fibroblasts was assessed by reverse transcription-quantitative polymerase chain reaction (RT-qPCR), western blotting, and immunofluorescence. The incidence of autophagy was assessed by flow cytometry. After knockdown using small interfering RNA targeting Beclin1, the expression of osteogenic differentiation genes were compared in spinal ligament fibroblasts. RESULTS: In clinical specimens, mRNA expression levels of microtubule-associated protein 1 light chain 3 and Beclin1 were higher in the OPLL group compared with the non-OPLL group. Pearson correlation analysis demonstrated that Beclin1 expression was positively correlated with expression of osteocalcin (OCN) (r = 0.8233, P < 0.001), alkaline phosphatase, biomineralization associated (ALP) (r = 0.7821, P < 0.001), and collagen type 1 (COL 1) (r = 0.6078, P = 0.001). Consistently, the upregulation of autophagy-associated genes in ligament fibroblasts from patients with OPLL were further confirmed by western blotting and immunofluorescence. The incidence of autophagy was also increased in ligament fibroblasts from patients with OPLL. Furthermore, knockdown of Beclin1 led to a decrease in the expression of OCN, ALP, and COL 1 by 63.2% (P < 0.01), 52% (P < 0.01), and 53.2% (P < 0.01) in ligament fibroblasts from patients with OPLL, respectively. CONCLUSIONS: Beclin1-mediated autophagy was involved in the osteogenic differentiation of ligament fibroblasts and promoted the development of OPLL.

Durotaxis Index of 3T3 Fibroblast Cells Scales with Stiff-to-Soft Membrane Tension Polarity.

Cell durotaxis is an essential process in tissue development. Although the role of cytoskeleton in cell durotaxis has been widely studied, whether cell volume and membrane tension are implicated in cell durotaxis remains unclear. By quantifying the volume distribution during cell durotaxis, we show that the volume of 3T3 fibroblast cells decreases by almost 40% as cells migrate toward stiffer regions of gradient gels. Inhibiting ion transporters that can reduce the amplitude of cell volume decrease significantly suppresses cell durotaxis. However, from the correlation analysis, we find that durotaxis index does not correlate with the cell volume decrease. It scales with the membrane tension difference in the direction of stiffness gradient. Because of the tight coupling between cell volume and membrane tension, inhibition of Na+/K+ ATPase and Na+/H+ exchanger results in smaller volume decrease and membrane tension difference. Collectively, our findings indicate that the polarization of membrane tension is a central regulator of cell durotaxis, and Na+/K+ ATPase and Na+/H+ exchanger can help to maintain the membrane tension polarity.

Does anxiety influence the prognosis of percutaneous transforaminal endoscopic discectomy in the treatment of lumbar disc herniation? A preliminary propensity score matching analysis.

PURPOSE: Previous reports revealed a correlation between psychological problems and spinal surgery. There is a lack of knowledge on the effect of anxiety on the percutaneous transforaminal endoscopic discectomy (PTED) outcome at the two year follow-up. The purpose of this study is to investigate changes in anxiety after PTED among patients with lumbar disc herniation (LDH), to compare the effect of anxiety on the prognosis using propensity score matching analysis, and to identify the related parameters of anxiety. METHODS: A total of 145 patients with LDH requiring PTED surgery were included. Twenty-six LDH patients with anxiety were matched with 26 control patients utilizing propensity score matching analysis. The demographic and peri-operative data were collected and analyzed. A correlation analysis was utilized. RESULTS: Both groups achieved significant improvements in visual analogue scale (VAS) scores for pain, Japanese Orthopedic Association (JOA) scores for neurological deficit, and 36-item Short-Form Health Survey (SF-36) scores and Oswestry Disability Index (ODI) scores for quality of life. A statistical difference was detected between the pre-operative and the post-operative Zung Self-Rating Anxiety Scale scores in the anxiety cohort. However, the difference between the anxiety group and the control group was statistically significant in the aforementioned parameters. The VAS, JOA, ODI and the SF-36 scores, and the disease duration were associated with pre-operative anxiety. CONCLUSION: PTED may provide significant improvements in clinical outcomes and symptoms of anxiety. A negative impact on the patient's prognosis may be caused by the presence of anxiety. Pain severity, neurological deficit, disease duration, and quality of life were associated with anxiety.

The roles of autophagy in osteogenic differentiation in rat ligamentum fibroblasts: Evidence and possible implications.

Autophagy, a macromolecular degradation process, plays a pivotal role in cell differentiation and survival. This study was designed to investigate the role of autophagy in the osteogenic differentiation in ligamentum fibroblasts. Rat ligamentum fibroblasts were isolated from the posterior longitudinal ligament and cultured in osteogenic induction medium. Ultrastructural analysis, immunofluorescence assay, western blot, flow cytometry, and lysosomal activity assessment were performed to determine the presence and activity of autophagy in the cells. The mineralization deposit and osteogenic gene expressions were evaluated to classify the association between autophagy activity and the bone formation ability of the spinal ligament cells. The influence of leptin and endothelin-1 on the autophagy activity was also evaluated. Our study demonstrated that autophagy was present and increased in the ligament cells under osteogenic induction. Inhibition of autophagy with either pharmacologic inhibitors (Bafilomycin A and 3-methyladenine) or Belcin1 (BECN1) knocking down weakened the mineralization capacity, decreased the gene expressions of COL1A1, osteocalcin (Ocn), and runt-related transcription factor 2 (Runx2) in the ligamentum fibroblasts and increased cell apoptosis. The Adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPK)-BECN1 autophagic pathway was activated in the osteogenic differentiating ligamentum fibroblasts. Leptin significantly increased the autophagy activity in the ligament cells under osteogenic induction. These discoveries might improve our understanding for the mechanism of ossification of the posterior longitudinal ligament (OPLL) and provide new approaches on the prevention and treatment of this not uncommon disease.