Study on the mechanism of action of Saposhnikovia divaricata and its key phytochemical on rheumatoid arthritis based on network pharmacology and bioinformatics.

ETHNOPHARMACOLOGICAL RELEVANCE: Saposhnikovia divaricata (Turcz.) Schischk (SD; called "fangfeng" in China) has been widely used in the clinical treatment of rheumatoid arthritis (RA) and has shown well therapeutic effects, but the specific mechanisms of action of its bioactive phytochemicals remain unclear. AIM OF THE STUDY: This study aimed to investigate the molecular biological mechanism of SD in treating RA through a pharmacology-based strategy. The SD-specific core ingredient Prangenidin was screened for further in-depth study. MATERIALS AND METHODS: The bioactive phytochemicals of SD and potential targets for the treatment of RA were screened by network pharmacology, and phytochemicals-related parameters such as pharmacology, and toxicology were evaluated. The protein interaction network was established to screen the core targets, and the correlation between the core targets and RA was further validated by bioinformatics strategy. Finally, molecular docking of core components and corresponding targets was performed. The in vitro experiments were performed to elucidate the regulation of Prangenidin on MH7A cells and on the PI3K/AKT pathway, and the in vivo therapeutic effect of Prangenidin was validated in collagen-induced arthritis (CIA) mice. RESULTS: A total of 18 bioactive phytochemicals and 66 potential target genes intersecting with the screened RA disease target genes were identified from SD. Finally, core ingredients such as wogonin, beta-sitosterol, 5-O-Methylvisamminol, and prangenidin and core targets such as PTGS2, RELA, and AKT1 were obtained. The underlying mechanism of SD in treating RA might be achieved by regulating pathways such as PI3K/AKT, IL-17 pathway, apoptosis, and multiple biological processes to exert anti-inflammatory and immunomodulatory effects. Molecular docking confirmed that all core ingredients and key targets had great docking activity. Prangenidin inhibited viability, migration, and invasion, and induced apoptosis in MH7A cells. Prangenidin also reduced the production of IL-1ß, IL-6, IL-8, MMP-1, and MMP-3. Molecular analysis showed that Prangenidin exerts its regulatory effect on MH7A cells by inhibiting PI3K/AKT pathway. Treatment with Prangenidin ameliorated synovial inflammation in the joints of mice with CIA. CONCLUSION: Our findings provide insights into the therapeutic effects of SD on RA, successfully predicting the effective ingredients and potential targets, which could suggest a novel theoretical basis for further exploration of its molecular mechanisms. It also revealed that Prangenidin inhibited viability, migration, invasion, cytokine, and MMPs expression, and induced apoptosis in RA FLSs via the PI3K/AKT pathway.

[Robot-assisted PVP for the treatment of osteoporotic fractures of the upper thoracic vertebra].

OBJECTIVE: To investigate the clinical effect of "Tianji" orthopedic robot-assisted percutaneous vertebro plasty(PVP) surgery in the treatment of upper thoracic osteoporotic fracture. METHODS: A retrospective analysis was performed on 32 patients with upper thoracic osteoporotic fracture who underwent PVP surgery in Shenzhen Hospital of Traditional Chinese Medicine from August 2016 to June 2022. There were 8 males and 24 females, ranging in age from 58 to 90 years old, with a mean of (67.75±12.27) years old. Fifteen patients were treated with robot-assisted PVP surgery (robot group), including 3 males and 12 females, with an average age of (68.5±10.3) years. Fracture location:1 case of T2 fracture, 1 case of T3 fracture, 3 cases of T4 fracture, 3 cases of T5 fracture, and 7 cases of T6 fracture. The follow-up period ranged from 1.0 to 3.0 months, with a mean of (1.6±0.7) months. Seventeen patients underwent routine PVP surgery (conventional group), including 5 males and 12 females, with an average age of (66.8±11.6) years old. Fracture location:1 case of T1 fracture, 5 cases of T4 fracture, 2 cases of T5 fracture and 9 cases of T6 fracture. The follow-up period ranged from 0.5 to 4.0 months, with a mean of (1.5±0.6) months. Preoperative and postoperative visual analogue scale(VAS) and Oswestry disability index(ODI) scores were compared between the two groups, and the number of punctures, perspective times, operation time, intraoperative blood loss, bone cement distribution, bone cement leakage, and intraoperative radiation dose were compared between the two groups. RESULTS: Number of punctures times, perspective times, operation time, intraoperative blood loss, bone cement distribution, bone cement leakage and intraoperative radiation dose in the robot group were all significantly better than those in the conventional group(P<0.05). VAS of 2.03±0.05 and ODI of (22.16±4.03) % in the robot group were significantly better than those of the robot group before surgery, which were (8.67±0.25) score and (79.40±7.72)%(t=100.869, P<0.001;t=25.456, P<0.001). VAS of 2.17±0.13 and ODI of (23.88±6.15)% in the conventional group were significantly better than those before surgery, which were (8.73±0.18) score and (80.01±7.59)%(t=121.816, P<0.001;t=23.691, P<0.001). There was no significant difference in VAS and ODI between the two groups after operation (t=-3.917, P=0.476;t=-0.922, P=0.364). CONCLUSION: Robot-assisted PVP in the treatment of upper thoracic osteoporotic fractures can further improve surgical safety, reduce bone cement leakage, and achieve satisfactory clinical efficacy.

[Feasibility of enlarging the ventral space by using a drill under spinal endoscopy in the treatment of severe free lumbar disc herniation].

OBJECTIVE: To evaluate the clinical efficacy of spinal endoscopy in the treatment of severe free lumbar disc herniation and explore the feasibility and application of microscopic drills to expand ventral space. METHODS: Thirty patients with severe free lumbar intervertebral disc herniation treated by spinal endoscopic technique from April 2019 to March 2021 were collected, including 19 males and 11 females;aged from 19 to 76 years with an average of (44.03±16.92) years old. All patients had a single segmental lesion with prolapse of the nucleus pulposus. Among them, there were 3 cases on L2,3, 3 cases on L3,4, 15 cases on L4,5, and 9 cases on L5S1. During operation, posterior bone of vertebral body and pedicle notch were removed by a drill under the endoscope to enlarge the ventral space. And the free nucleus pulposus was exposed and completely removed. The intraoperative blood loss, operation time, hospital stay and postoperative neurological complications were recorded, and Japanese Orthopaedic Association (JOA) score, Oswestry Disability Index (ODI) and visual analogue scale (VAS) were compared before operation, 2 days, 3 months and 1 year after operation, and Macnab standard was used to evaluate clinical efficacy. RESULTS: All operations were successful and the free nucleus pulposus was completely removed. Pain in the lower back and legs was significantly relieved on the day after operation. Two patients experienced transient pain and numbness in lower limbs after operation, and no serious nerve injury complications occurred. ODI and VAS at each time point after surgery were significantly lower than those before surgery (P<0.01), and JOA score was significantly higher than before surgery (P<0.01). The excellent and good rates of Macnab were 66.67% (20/30), 83.33% (25/30) and 90.00% (27/30) on 2 days, 3 months and 1 year after operation, respectively. CONCLUSION: For severe free lumbar intervertebral disc herniation, using of a drill under endoscope to expand the ventral space can smoothly remove the free nucleus pulposus and avoid nerve damage.

Curcumol Alleviates the Inflammation of Nucleus Pulposus Cells via the PI3K/Akt/NF-κB Signaling Pathway and Delays Intervertebral Disk Degeneration.

BACKGROUND: Intervertebral disk degeneration (IVDD) is closely associated with inflammatory environments. Curcumol has been shown to alleviate inflammation in various disease models, but its effects on IVDD remain unclear. In this study, we sought to determine the mechanism of curcumol in tumor necrosis factor (TNF)-α-induced nucleus pulposus cells and a mouse IVDD model. METHODS: Nucleus pulposus cells were pretreated with curcumol and then exposed to TNF-α. Cell viability was analyzed using CCK-8, and the messenger ribonucleic acid and protein levels of inflammatory cytokines and PI3K/Akt/NF-κB-related signaling molecules were detected using real-time polymerase chain reaction, enzyme-linked immunosorbent assay, and western blotting. The mouse IVDD model was established by puncturing the C6/7 level of the caudal spine, and then it was treated with curcumol after surgery. Alcian blue/orange G staining was performed to evaluate the severity of intervertebral disk damage, and immunohistochemistry was performed to detect the expression of TNF-α. Toxicologic effects of curcumol were measured by performing hematoxylin-eosin staining and enzyme-linked immunosorbent assay. RESULTS: Curcumol reduced IL-1ß, IL-6, and TNF-α production in NPCs, and the phosphorylation of proteins in the PI3K/Akt/NF-κB signaling pathway was also decreased. The PI3K/Akt/NF-κB-related signaling molecules decreased when TNF-α-induced NPCs were treated with a PI3K inhibitor; however, curcumol did not reverse these effects. In vivo, curcumol ameliorated the progression of IVDD at the early stage and did not exert toxicologic effects. CONCLUSIONS: These results suggest a potential therapeutic use of curcumol to alleviate inflammation via the PI3K/Akt/NF-κB signaling pathway and delay the progression of IVDD.

[Analysis on clinical effects of two surgical approaches in percutaneous spinal endoscopy for L5S1 disc herniation].

OBJECTIVE: To analyze the clinical effects, complications and operational key points of the percutaneous endoscopic transforaminal discectomy (PETD) and percutaneous endoscopic interlaminar discectomy (PEID) in treating L5S1 disc herniation. METHODS: The clinical data of 158 patients with L5S1 disc herniation treated from July 2015 to March 2018 were restospectively analyzed. According to different surgical approaches, the patients were divided into PETD group or PEID group, 79 cases in each group. In PETD group, there were 41 males and 38 females, with an average age of (41.38±6.25) years and course of disease of (10.06±3.14) months. In PEID group, there were 43 males and 36 females, with an average age of (41.18±5.78) years and course of disease of (9.99±2.83) months. The operation length, intraoperative blood loss, intraoperative fluoroscopy times, days of hospital stay, and complications were recorded between two groups. Visual analogue score (VAS), Japanese Orthopedic Association(JOA) score, Oswestry Disability Index(ODI), modified Macnab criteria were used to assessed clinical effects after operation. RESULTS: All patients completed surgery and were followed up for more than 1 year. (1) There were no significant differences in the intraoperative blood loss or hospitalization length between two groups(P>0.05). The operation length and intraoperative fluoroscopy times in PETD group were significantly higher than in PEID group (P<0.05). (2)VAS, JOA scores, ODI at 1 week, 6 months, or 12 months after operation were significantly improved between two groups (P<0.05), but there was no statistical significance between two groups(P>0.05). (3)The excellence rate was 89.87% (71 / 79) in PETD group and 87.34% (69 / 79) in PEID group at the latest follow-up, with no statistical significance(P>0.05). (4)Complications occurred in 2 cases in PETD group and in 3 cases in PEID group, with no significant differences between two groups. CONCLUSION: The short term efficacy of the PETD is equal to that of the PEID for the L5S1 disc herniation, but PEID is superior in the operation length, the access of stereotaxic puncture and intraoperative fluoroscopy times. The complications can be effectively reduced by following the indications, mastering the endoscopic technique, operating carefully and being familiar with the key points of common complications.

Combining YESS and TESSYS techniques during percutaneous transforaminal endoscopic discectomy for multilevel lumbar disc herniation.

The authors retrospectively characterized the clinical outcomes of combining the Yeung endoscopic spine system (YESS) and transforaminal endoscopic surgical system (TESSYS) techniques during percutaneous transforaminal endoscopic discectomy (PTED) to treat multilevel lumbar disc herniation.PTED using both YESS and TESSYS was performed on 52 patients with multilevel lumbar disc herniations who had shown no apparent response to previous conservative treatments. Postsurgical follow-ups were conducted at weeks 1, 26, and 48. Patients' preoperative and postoperative performances were assessed by modified MacNab classification, Japanese Orthopedic Association (JOA) scores, Oswestry disability index (ODI), and visual analog scale (VAS), and compared with 34 and 45 patients who were treated only by YESS and TESSYS, respectively.The postsurgery surgeon-performed assessment showed satisfactory results in 98% of the YESS + TESSYS-treated cases. The average operative time was 116 ±â€Š23 minutes, intraoperative bleeding was 19 ±â€Š12 mL, and bed stay was 3 days. No complications occurred, including infection, nerve injury, or spinal canal hematoma. One week after surgery, the modified MacNab classifications of the patients were excellent in 45, good in 6, fair in 1, and poor in 0 (98% were excellent or good). JOA, ODI, and VAS scores for low back pain significantly improved relative to the preoperative assessment (P < .01) and had remained stable at 26 and 48 weeks.PTED that combined YESS and TESSYS techniques, depending on the predominant type of lumbar disc herniation at individual levels, is safe, minimally invasive, and effective.

A Randomized Trial Comparing Clinical Outcomes Between Zero-Profile and Traditional Multilevel Anterior Cervical Discectomy and Fusion Surgery for Cervical Myelopathy.

STUDY DESIGN: Prospective randomized study from a single center OBJECTIVE.: The purpose of this study was to compare outcomes between a zero-profile (ZP) anterior cervical discectomy and fusion (ACDF) construct to a traditional ACDF with anterior cervical plate (ACP) in the treatment of multilevel cervical spondylotic myelopathy. SUMMARY OF BACKGROUND DATA: Multilevel cervical spondylotic myelopathy can be treated by a variety of techniques, most commonly with corpectomy, ACDF, posterior cervical fusion, or a combination of the three. Examples in the literature of comparative effectiveness of different anterior approach types are few. METHODS: A total of 104 patients with multilevel cervical spondylotic myelopathy were randomized in equal proportion between treated with ACDF and ZP or ACDF with ACP. Clinical efficacy of two groups was evaluated preoperatively and at all postoperative time points through 2 years postoperative by the Japanese Orthopedic Association score and the neck disability index. Radiographic changes from baseline, including disc height and cervical lordosis, were evaluated at the same postoperative time points. Complications were assessed perioperatively and through 2 years postoperatively. RESULTS: The ZP and ACP ACDF groups demonstrated substantially equivalent Japanese Orthopaedic Association, neck disability index, disc height, and lordosis improvements from baseline, which were maintained through 2 years postoperatively. Complications occurred in 4% of ZP and 17% of ACP patients (P = 0.052), and zero (0%) ZP and four (8%) ACP patients reported hoarseness or dysphagia. CONCLUSION: ZP used in multilevel ACDF may obtain favorable clinical outcomes and a lower postoperative complication. LEVEL OF EVIDENCE: 2.

Long non-coding RNA UCA1 contributes to the progression of oral squamous cell carcinoma by regulating the WNT/ß-catenin signaling pathway.

With the development of functional genomics studies, a mass of long non-coding RNAs (LncRNA) were discovered from the human genome. Long non-coding RNAs serve as pivotal regulators of genes that are able to generate LncRNA-binding protein complexes to modulate a great number of genes. Recently, the LncRNA urothelial carcinoma-associated 1 (UCA1) has been revealed to be dysregulated, which plays a critical role in the development of a few cancers. However, the role of the biology and clinical significance of UCA1 in the tumorigenesis of oral squamous cell carcinoma (OSCC) remain unknown. We found that UCA1 expression levels were upregulated aberrantly in tongue squamous cell carcinoma tissues and associated with lymph node metastasis and TNM stage. We explored the expression, function, and molecular mechanism of LncRNA UCA1 in OSCC. In the present work, we revealed that UCA1 silencing suppressed proliferation and metastasis and induced apoptosis of OSCC cell lines in vitro and in vivo, which might be related to the activation level of the WNT/ß-catenin signaling pathway. Our research results emphasize the pivotal role of UCA1 in the oncogenesis of OSCC and reveal a novel LncRNA UCA1-ß-catenin-WNT signaling pathway regulatory network that could contribute to our understanding in the pathogenesis of OSCC and assist in the discovery of a viable LncRNA-directed diagnostic and therapeutic strategy for this fatal disease.

[ESTABLISHMENT OF INTERVERTEBRAL DISC DEGENERATION OF RABBITS BY USING MINIMALLY INVASIVE ACUPUNCTURE AND ROTARY-CUTTING].

OBJECTIVE: To investigate the feasibility of establishing intervertebral disc degeneration (IDD) model by using minimally invasive acupuncture and rotary-cutting. METHODS: Forty New Zealand white rabbits [male or female, (2.9 ± 0.3) kg in weight] were randomly divided into control group (n = 20) and experimental group (n = 20). No treatment was done in the control group; percutaneous puncture was performed on L4,5 and L5,6 intervertebral disc by using 18G needle under C-arm X-ray monitoring for rotary-cutting of nucleus pulposus to promote degeneration of the disc in the experimental group. At 4, 8, 12, and 16 weeks after operation, general observation and MRI observation were done, and intervertebral disc degeneration was accessed based on Pfirrmann grade; the specimens were harvested for Masson staining and Safranine O staining. RESULTS: The nucleus pulposus showed dark colors and reduced elasticity in the experimental group when compared with the control group. T2-weighted MRI images indicated that the disc signal intensity of control group had no obvious change at early stage, and weakened slightly at late stage; disc signal intensity of the experimental group decreased with time. According to Pfirrmann grade for disc degeneration, disc degeneration degree was significantly aggravated with time in 2 groups (P < 0.05); degeneration was significantly more severe in the experimental group than the control group at the other time points (P < 0.05) except 4 weeks (P > 0.05). Masson staining results showed that irregular arrangement of annulus with integrate structure was observed in the control group with time; the annulus of the experimental group arranged in disorder, or even disc fibrous circle rupture appeared with time. Safranin O staining showed that the nucleus pulposus cells reduced significantly in the experimental group, but did not in the control group. CONCLUSION: Minimally invasive acupuncture and rotary-cutting could successfully establish the IDD model in rabbits.