Exosomal lncRNA HCP5 derived from human bone marrow mesenchymal stem cells improves chronic periodontitis by miR-24-3p/HO1/P38/ELK1 pathway.

Objective: The present study aimed to explore the function of human bone marrow mesenchymal stem cells (hBMMSCs)-derived exosomal long noncoding RNA histocompatibility leukocyte antigen complex P5 (HCP5) in the osteogenic differentiation of human periodontal ligament stem cells (hPDLSCs) to improve chronic periodontitis (CP). Methods: Exosomes were extracted from hBMMSCs. Alizarin red S staining was used to detect mineralised nodules. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was used to measure HCP5 and miR-24-3p expression. The mRNA and protein levels of alkaline phosphatase (ALP), osteocalcin, osterix, runt-related transcription factor 2, bone morphogenetic protein 2, osteopontin, fibronectin, collagen 1, heme oxygenase 1 (HO1), P38, and ETS transcription factor ELK1 (ELK1) were detected using RT-qPCR and Western blot. Enzyme-linked immunosorbent assay (ELISA) kits were used to determine the HO1 and carbon monoxide concentrations. Heme, biliverdin, and Fe2+ levels were determined using detection kits. Micro-computed tomography, hematoxylin and eosin staining, ALP staining, tartrate-resistant acid phosphatase staining, ELISA, and RT-qPCR were conducted to evaluate the effect of HCP5 on CP mice. Dual luciferase, RNA immunoprecipitation, and RNA pulldown experiments were performed to identify the interactions among HCP5, miR-24-3p, and HO1. Results: The osteogenic ability of hPDLSCs significantly increased when co-cultured with hBMMSCs or hBMMSCs exosomes. Overexpression of HCP5 and HO1 in hBMMSCs exosomes promoted the osteogenic differentiation of hPDLSCs, and knockdown of HCP5 repressed the osteogenic differentiation of hPDLSCs. HCP5 knockdown enhanced the inflammatory response and repressed osteogenesis in CP mice. MiR-24-3p overexpression diminished the stimulatory effect of HCP5 on the osteogenic ability of hPDLSCs. Mechanistically, HCP5 acted as a sponge for miR-24-3p and regulated HO1 expression, and HO1 activated the P38/ELK1 pathway. Conclusion: HBMMSCs-derived exosomal HCP5 promotes the osteogenic differentiation of hPDLSCs and alleviates CP by regulating the miR-24-3p/HO1/P38/ELK1 signalling pathway.

[Impact of Liparis nervosa extract on neuroinflammation mediated by LPS-induced BV-2 microglial cells and its bioactive components analysis].

To investigate the impact and potential mechanisms of extracts from different parts of Liparis nervosa on neuroinflammation by lipopolysaccharide(LPS)-induced BV-2 microglial cells. The materials of L. nervosa were subjected to crushing, ethanol extraction, and concentration to obtain an alcohol extract. Subsequently, the extract was further extracted to obtain petroleum ether extract, ethyl acetate extract, N-butanol extract, and aqueous phase extract. The ethyl acetate extract was separated into distillate(1)-(6)using D101 macroporous resin column chromatography. The experiment was divided into control group, LPS model group, L. nervosa extract group, and LPS + L. nervosa group. LPS was utilized to induce a neuroinflammatory cell model in BV-2 microglial cells. The Griess test was utilized for detecting the production of nitric oxide(NO) in the cell supernatant. Cell viability was detected by MTT assay. The release of interleukin-6(IL-6) and tumor necrosis factor alpha(TNF-α) in the cell supernatant was quantified using ELISA.RT-qPCR was utilized to assess the m RNA levels of pro-inflammatory cytokines inducible nitric oxide synthase(iNOS), cyclooxygenase-2(COX-2), interleukin( IL)-6, IL-1ß, and TNF-α. The protein expression of i NOS, COX-2, nuclear factor kappa-B p65(p65), p-p65, extracellular signal-regulated kinase(ERK), p-ERK, c-jun N-terminal kinase(JNK), p-JNK, p38 mitogen-activated protein kinase(p38), and p-p38 MAPK(p-p38) were also evaluated by Western blot. The chemical composition of active substances in L. nervosa was analyzed using the UHPLC-Q-Exactive Orbitrap technology and literature comparison. Our findings indicate that extracts from different parts of L. nervosa exhibit a significant reduction in the release of NO from LPS-induced BV-2 microglial cells.Specifically, the ethyl acetate extract demonstrates the most notable inhibitory effect without causing cell toxicity. Additionally, the distillate(6) extracted from the ethyl acetate exhibits a reduction in the m RNA and protein levels of i NOS, COX-2, IL-6, IL-1ß, and TNF-α in a dose-dependent manner, and it inhibits the protein expression of p-p65, p-ERK, p-p38, and p-JNK in LPS-induced BV-2 microglial cells. A total of 79 compounds in the distillate(6) were identified by mass spectrometry, including 12 confirmed compounds with anti-inflammatory effects. This study confirmed the remarkable efficacy of L. nervosa extract in the treatment of neuroinflammation, which may be achieved through the inhibition of NF-κB and MAPK signaling pathways.

Ropivacaine prompts ferroptosis to enhance the cisplatin-sensitivity of human colorectal cancer through SIRT1/Nrf2 signaling pathway.

The ineffectiveness of cisplatin therapy in treating colorectal cancer (CRC) is attributed to an increase of resistance. It's necessary to investigate adjunctive agents capable of enhancing drug efficacy. Previous studies have shown that ropivacaine inhibit the growth of various cancer cells, but its impact on cisplatin resistance in tumors is not well understood. This study was to illustrate the impact and mechanism of ropivacaine enhanced cisplatin-sensitivity of CRC. Cisplatin alone treatment resulted in the elevation of reactive oxygen species (ROS) and intracellular Fe2+ levels, as well as a reduction in mitochondrial membrane potential (MMP) in cisplatin-sensitive LOVO cells, while these effects were mitigated in the cisplatin-resistant LOVO/DDP cells. The co-administration of ropivacaine with cisplatin inhibited cell viability and cell migration, decreased MMP, and promoted ROS accumulation and apoptosis in both LOVO cells and LOVO/DDP cells. And they upregulated the levels of ferroptosis makers and downregulated the expression of anti-ferroptosis proteins. However, this effect was reversed by ferroptosis inhibitor ferrostatin-1 or liproxstatin-1. Furthermore, we o demonstrated that the co-administration of ropivacaine and cisplatin resulted in a decrease in SIRT1 expression, and SIRT1 knockdown in LOVO/DDP cells enhanced the ferroptosis and the anti-tumor properties of ropivacaine, while also inhibiting the activation of the Nrf2/Keap1 pathway. The above results suggested that ropivacaine increased the sensitivity of CRC cells to cisplatin by promoting ferroptosis through the inhibition of SIRT1 expression, which proposes a therapeutic approach for overcoming cisplatin resistance in CRC.

Macrophage migration inhibitor factor (MIF): Potential role in cognitive impairment disorders.

Macrophage migration inhibitory factor (MIF) is a cytokine in the immune system, participated in both innate and adaptive immune responses. Except from immune cells, MIF is also secreted by a variety of non-immune cells, including hematopoietic cells, endothelial cells (ECs), and neurons. MIF plays a crucial role in various diseases, such as sepsis, rheumatoid arthritis, acute kidney injury, and neurodegenerative diseases. The role of MIF in the neuropathogenesis of cognitive impairment disorders is emphasized, as it recruits multiple inflammatory mediators, leading to activating microglia or astrocyte-derived neuroinflammation. Furthermore, it contributes to the cell death of neurons and ECs with the binding of apoptosis-inducing factor (AIF) through parthanatos-associated apoptosis-inducing factor nuclease (PAAN) / MIF pathway. This review comprehensively delves into the relationship between MIF and the neuropathogenesis of cognitive impairment disorders, providing a series of emerging MIF-targeted pharmaceuticals as potential treatments for cognitive impairment disorders.

Different doses of bevacizumab in combination with chemotherapy for advanced colorectal cancer: a meta-analysis and Bayesian analysis.

OBJECTIVE: The aim of the present study was to explore the incremental benefit of bevacizumab (Bev) in the treatment of advanced colorectal cancer (CRC) with different doses. METHODS: A literature search of eight electronic databases (China National Knowledge Infrastructure, Wanfang databases, Chinese Biomedical Database, VIP medicine information, Cochrane Library, MEDLINE, PubMed, and EMBASE) was conducted from database creation to December 2022. Randomized controlled trials (RCTs) that compared Bev at various dosages + chemotherapy (CT) versus placebo (or blank control) + CT were selected. The overall survival (OS), progression-free survival (PFS), overall response rate (ORR; complete response [CR] + partial response [PR]), and grade ≥ 3 adverse events (AEs) were integrated first by pooled analysis. The likelihood of ideal dosage of Bev was then ranked using random effects within Bayesian analysis. RESULTS: Twenty-six RCTs involving 18,261 patients met the inclusion criteria. OS increased significantly after using 5 mg (HR: 0.87, 95% CI 0.75 to 1.00) and 10 mg dosages of Bev (HR: 0.75, 95% CI 0.66 to 0.85) with CT, but statistical significance was not attained for the 7.5 mg dose (HR: 0.95, 95% CI 0.83 to 1.08). A significantly increased in PFS with doses of 5 mg (HR: 0.69, 95% CI 0.58 to 0.83), 7.5 mg (HR: 0.81, 95% CI 0.66 to 1.00), and 10 mg (HR: 0.60, 95% CI 0.53 to 0.68). ORR distinctly increased after 5 mg (RR: 1.34, 95% CI 1.15 to 1.55), 7.5 mg (RR: 1.25, 95% CI 1.05 to 1.50), and10 mg (RR: 2.27, 95% CI 1.82 to 2.84) doses were administered. Grade ≥ 3 AEs increased clearly in 5 mg (RR: 1.11, 95% CI 1.04 to 1.20) compared to 7.5 mg (RR: 1.05, 95% CI 0.82 to 1.35) and 10 mg (RR: 1.15, 95% CI 0.98 to 1.36). Bayesian analysis demonstrated that 10 mg Bev obtained the maximum time of OS (HR: 0.75, 95% CrI 0.58 to 0.97; probability rank = 0.05) indirectly compared to 5 mg and 7.5 mg Bev. Compared with 5 mg and 7.5 mg Bev, 10 mg Bev also holds the longest duration for PFS (HR: 0.59, 95% CrI 0.43 to 0.82; probability rank = 0.00). In terms of ORR, 10 mg Bev holds the maximum frequency (RR: 2.02, 95% CrI 1.52 to 2.66; probability rank = 0.98) in comparison to 5 mg and 7.5 mg Bev clearly. For grade ≥ 3 AEs, 10 mg Bev has the maximum incidence (RR: 1.15, 95% CrI 0.95 to 1.40, probability rank = 0.67) in comparison to other doses of Bev. CONCLUSION: The study suggests that 10 mg dose Bev could be more effective in treating advanced CRC in efficacy, but 5 mg Bev could be more safer in terms of safety.

Both-Column Acetabular Fractures: Should Pelvic Ring Reduction or Acetabulum be Performed First?

OBJECTIVE: Both-column acetabular fracture is a type that accumulates both the pelvis and acetabulum with complex fracture line alignment and has variant fracture fragments. The selection of different reduction landmarks and sequences produces different qualities of reduction. This study aims to compare the operation-related items, quality of reduction, and hip functional outcome by using different reduction landmarks and sequences for management of both-column acetabular fractures (BCAF). METHODS: A consecutive cohort of 42 patients from January 2013 to January 2019 with BCAF were treated operatively with different reduction landmarks and sequences: pelvic ring fractures reduction first (PRFRF group) and acetabular fractures reduction first (AFRF group). Preoperative computer visual surgical procedures were applied. There were 22 patients in PRFRF group and 20 patients in AFRF group. The surgical details, complications, radiographic and clinical results were recorded. The quality of reduction was assessed by the Matta scoring system. The functional outcome was evaluated by the modified Merle d'Aubigné and Postel scoring system. The measurement data were analyzed using the t-test of independent samples and rank-sum test of ranked data. RESULTS: The real reduction sequence in both groups was almost identical to the preoperative surgical procedures. The excellent/good quality of reduction in PRFRF group (21/22) was better than AFRF group (17/20). Operative time (152.3 ± 16.3 mins) and intra-operative blood loss (639.5 ± 109.9ml) were significantly reduced in PRFRF group (p < 0.05). The incidence of deep vein thrombosis in PRFRF group (2/22) was less than AFRF group (4/20), but without statistical signification. CONCLUSION: Selection of an appropriate reduction landmark and sequence could result in better quality of reduction, operative time, and decreased blood loss during treatment of BCAF.

The novel infra-pectineal buttress plates used for internal fixation of elderly quadrilateral surface involved acetabular fractures.

OBJECTIVES: In geriatric acetabular fractures, the quadrilateral surface (QLS) was frequently involved in acetabular fracture patterns and accompanied by medial displacement. It was important to buttress the medial displaced QLS and reconstruct the congruity of the affected acetabulum. To evaluate the clinical effectiveness of the novel infra-pectineal quadrilateral surface buttress plates for the treatment of geriatric acetabular fractures. METHODS: Twenty-three geriatric patients who were treated for acetabular fractures involving QLS with the novel infra-pectineal buttress plates (NIBP) through a single supra-ilioinguinal approach between January 2015 and June 2019 were retrospectively analyzed; all patients received at least 1 year's follow-up. All patients were aged ≥60 years old and including 18 males and five females. Radiologic and clinical outcomes of patients involved in the study were collated and analyzed according to the Matta scoring system and the Merle D'Aubigné-Postel scoring system. The functional recovery scoring was compared using q-test. RESULTS: All 23 consecutive patients had relatively satisfactory clinical treatment effectiveness. Average ages, length of incision, operation time, and intraoperative blood loss were 69.8 ± 6.1 years, 12.1 ± 2.6 cm, 166.5 ± 43.5 min, and 500 (500,700) ml, respectively. According to the Matta scoring system, 14 cases of reduction were graded as excellent, five as good, and four as fair. At the last follow-up, the clinical outcome evaluation was excellent in 13 cases, good in seven cases, and poor in three cases with the use of the Merle D'Aubigné-Postel scoring system. The difference of modified Merle D'Aubigne-Postel score at 3 months, 6 months and last follow up was statistically significant (F = 21.56, p < 0.05). Postoperative lateral femoral cutaneous nerve injury occurred in three patients and heterotopic ossification occurred in one patient. CONCLUSIONS: For the treatment of geriatric acetabular fractures, the NIBP could provide stable and effective fixation to the QLS involved acetabular fractures, and related satisfactory clinical results with few complications were noted.

Melatonin Attenuates Ropivacaine-Induced Apoptosis by Inhibiting Excessive Mitophagy Through the Parkin/PINK1 Pathway in PC12 and HT22 Cells.

Melatonin, as an endogenous circadian indoleamine secreted by the pineal gland, executes extensive biological functions, including antioxidant, anti-inflammatory, anti-tumor, and neuroprotective effects. Although melatonin has been reported to serve as a potential therapeutic against many nerve injury diseases, its effect on ropivacaine-induced neurotoxicity remains obscure. Our research aimed to explore the impact and mechanism of melatonin on ropivacaine-induced neurotoxicity. Our results showed that melatonin pretreatment protected the cell viability, morphology, and apoptosis of PC12 and HT22 cells, and it also improved ropivacaine-induced mitochondrial dysfunction and the activation of mitophagy. In addition, we found that autophagy activation with rapamycin significantly weakened the protective effect of melatonin against ropivacaine-induced apoptosis, whereas autophagy inhibition with 3-MA enhanced the effect of melatonin. We also detected the activation of Parkin and PINK1, a canonical mechanism for mitophagy regulation, and results shown that melatonin downregulated the expression of Parkin and PINK1, and upregulated Tomm20 and COXIV proteins, so that those results indicated that melatonin protected ropivacaine-induced apoptosis through suppressing excessive mitophagy by inhibiting the Parkin/PINK1 pathway. Melatonin may be a useful potential therapeutic agent against ropivacaine-induced neurotoxicity.

Ropivacaine Induces Cell Cycle Arrest in the G0/G1 Phase and Apoptosis of PC12 Cells via Inhibiting Mitochondrial STAT3 Translocation.

STAT3 has neuroprotective effect via non-canonical activation and mitochondrial translocation, but its effect on ropivacaine-induced neurotoxicity remains unclear. Our previous study revealed that apoptosis was an important mechanism of ropivacaine-induced neurotoxicity; this study is to illustrate the relationship between STAT3 with ropivacaine-induced apoptosis. Those results showed that ropivacaine treatment decreased cell viability, induced cell cycle arrest in the G0/G1 phase, apoptosis, oxidative stress, and mitochondrial dysfunction in PC12 cells. Moreover, ropivacaine decreased the phosphorylated levels of STAT3 at Ser727 and downregulated the expression of STAT3 upstream gene IL-6. The mitochondrial translocation of STAT3 was also hindered by ropivacaine. To further illustrate the connection of STAT3 protein structure with ropivacaine, the autodock-vina was used to examine the interaction between STAT3 and ropivacaine, and the results showed that ropivacaine could bind to STAT3's proline site and other sites. In addition, the activator and inhibitor of mitoSTAT3 translocation were used to demonstrate it was involved in ropivacaine-induced apoptosis; the results showed that enhancing the mitochondrial STAT3 translocation could prevent ropivacaine-induced apoptosis. Finally, the expression of p-STAT3 and the levels of apoptosis in the spinal cord were also detected; the results were consistent with the cell experiment; ropivacaine decreased the expression of p-STAT3 protein and increased the levels of apoptosis in the spinal cord. We demonstrated that ropivacaine induced apoptosis by inhibiting the phosphorylation of STAT3 at Ser727 and the mitochondrial STAT3 translocation. This effect was reversed by the activation of the mitochondrial STAT3 translocation.

Late Postoperative Cervical Spinal Cord Herniation with Pseudomeningocele.

We report a middle-aged man with a history of traumatic cervical spinal cord injury with extensive edema. Decompressive surgery of posterior laminectomy and fixation was performed. An irreparable dural rupture on dorsal-lateral side of the cord was found during operation. The patient was managed with a myofascial and fibrin glue assisted closure and underwent watertight closure of fascia and skin. No cerebrospinal fluid leakage was detected in the postoperative period and the wound was healing, thus the patient was discharged. Clinical symptoms resolved. Half a year later, however, the patient presented with C5 nerve palsy. Magnetic resonance imaging revealed cervical spinal cord herniation with pseudomeningocele. Late postoperative cervical spinal cord herniation with pseudomeningocele may occur in any cervical spine trauma cases with dural rupture and/or defect, and close follow-up and observation are needed in the postoperative period.

P53 inhibitor pifithrin-α inhibits ropivacaine-induced neuronal apoptosis via the mitochondrial apoptosis pathway.

The neurotoxicity of local anesthetics (LAs) has attracted more and more attention, However, they lack preventive and therapeutic measures. Many studies have shown that apoptosis plays an important role in the process of LA-induced neurotoxicity. As an important signaling molecule to activate apoptosis, p53 has been proved to be involved in the neurotoxicity induced by LAs, but the mechanism is unclear. In this study, we explored the effect of pifithrin-α (PFT-α), a p53 inhibitor, on apoptosis by ropivacaine (Rop) in vivo and in vitro. Cell viability and apoptosis detected by CCK-8 and a JC-1 apoptosis detection kit, the changes of spinal cord structure observed after hematoxylin and eosin staining, apoptosis of the spinal cord measured by terminal deoxynucleotidyl transferase dUTP nick end labeling staining, behavioral assessment of the nerve Injury evaluated by the detection of sciatic nerve conduction velocity (SNCV) andmechanical withdrawal threshold (MWT), the expression of p53 and many apoptosis-related genes included Bax, Bcl-2, and caspase-3 detected by quantitative real-time polymerase chain reaction, Western blot analysis, immunofluorescence, and immunohistochemistry. Results showed that PC12 cell viability decreased because of Rop, but the pretreatment of PFT-α could protect it. And PFT-α reduced the injuries in the spinal cord by Rop included vacuoles or edema. The results of immunofluorescence and immunohistochemistry testing showed that PFT-α inhibited the p53 protein upregulated by Rop. Apoptosis rate and many proapoptotic genes include p53, Bax, caspase-3 messenger RNA, and proteins were increased by Rop, but PFT-α could decrease it. In conclusion, PFT-α inhibited cell apoptosis and spinal cord injuries induced by Rop.

Internal fixation of anterior acetabular fractures with a limited pararectus approach and the anatomical plates: preliminary results.

BACKGROUND: The surgical treatment of acetabular fracture has adverse outcomes and high risk, and minimally invasive method is a good way to reduce complications and improve hip joint function. This study is to investigate the treatment of certain acetabular fractures primarily involving the anterior column and quadrilateral plate using a limited pararectus approach and the anatomical plates. METHODS: A consecutive cohort of 17 patients with anterior displaced acetabular fractures were managed operatively with a limited approach and the anatomical plates. Ten patients had anterior column fractures, 1 patient had anterior wall fracture, 4 patients had transverse fractures and 2 patients had anterior column with posterior hemi-transverse fractures. The inferior half of the pararectus approach was adopted to open the medial window and to access the anterior column and the quadrilateral plate. The anatomical plates were used for internal fixation. Residual displacements were assessed on the postoperative CT scans using a standardized digital method. The surgical details, hip functional outcomes, and complications were noted. RESULTS: All of the patients were operated using the limited pararectus approach and the anatomical plates successfully. The mean operative time and blood loss were 90.9 min and 334.1 ml, respectively. The average postoperative residual gap and step displacement on CT were 2.9 mm and 0.7 mm, respectively. The radiological outcome was estimated according to the Matta score, ten of the cases were graded anatomical, six were graded imperfect, and one was graded poor. Follow up averaged 15 months. Functional outcomes were excellent for nine, good for six, and fair for two. It was noted that one case of peritoneal injury was repaired intraoperatively. CONCLUSIONS: The limited pararectus approach with the advantages of less trauma, direct exposure to the anterior column and quadrilateral plate. The anatomical plates can fit with the surface of the acetabulum, which saves the time of remodeling plates during operation and facilitate fracture reduction. The combination approach can be a good choice for limited surgery of displaced anterior acetabular fractures especially involving the quadrilateral plate.

Treatment of anterior column posterior hemitransverse fracture with supra-ilioinguinal approach.

OBJECTIVE: To report the feasibility and effect of the supra-ilioinguinal approach for treatment of anterior posterior hemitransverse fracture of the acetabulum. METHODS: Nineteen consecutive patients who underwent treatment for an anterior column posterior hemitransverse fracture of the acetabulum from January 2013 to June 2018 were retrospectively analyzed. All patients underwent treatment by the single supra-ilioinguinal approach with at least 1 year of follow-up. RESULTS: The mean time to surgery, operative time, incision length, and blood loss were 10.2 ± 3.8 days, 157 ± 125 minutes, 10.2 ± 0.6 cm, and 876 ± 234 mL, respectively. According to the Matta scoring system, the reduction quality was excellent in 13 patients, good in 6, and poor in 0. According to the Merle d'Aubigné scoring system, the outcome at the last follow-up was excellent in 12 patients, good in 5, fair in 1, and poor in 1. Postoperative complications occurred in three patients (deep vein thrombosis in one, lateral femoral cutaneous nerve injury in one, and both complications in one). CONCLUSIONS: Use of the supra-ilioinguinal approach for treatment of anterior column posterior hemitransverse fracture of the acetabulum produced excellent clinical results because of the direct visualization of the anterior column and quadrilateral plate.

Resveratrol inhibits the progression of cervical cancer by suppressing the transcription and expression of HPV E6 and E7 genes.

Resveratrol is a representative polyphenol of diet­derived putative cancer chemopreventive agents, which have attracted increasing interest in the cancer chemoprevention community. The inhibition of the action of human papillomavirus (HPV) E6 and E7 has been considered a key approach for cervical cancer therapy. Resveratrol has been shown to induce the apoptosis, and reduce both the viability and mitotic index of a number of cancer cell lines, including human cervical cancer cells. In the present study, it was confirmed that resveratrol inhibited the HPV E6 mRNA, HPV E6 protein and phosphorylated retinoblastoma protein (p­pRb1) levels, and increased the p53 protein levels in HeLa and Ca Ski cells, as well as in subcutaneous tumor tissue grown from HeLa cells. High­risk HPV uses a bicistronic RNA to control E6 and E7 genes simultaneously. On the whole, the present study demonstrates that resveratrol inhibits cervical cancer development by suppressing the transcription and translation of E6 and E7, and also by promoting the apoptosis and G1/S phase transition arrest. These findings may provide the basis for the development of resveratrol as a candidate for cervical cancer therapy.

Resveratrol suppresses the growth and metastatic potential of cervical cancer by inhibiting STAT3Tyr705 phosphorylation.

Aberrant signal transducer and activator of transcription 3 (STAT3) signaling promotes the initiation and progression of cancer in humans by either inhibiting apoptosis or inducing cell proliferation, angiogenesis, invasion, and metastasis. The role of resveratrol（RES）in inhibiting the STAT3 signaling pathway in vivo, particularly in cervical cancer is still unknown. This study aims to investigate the role of STAT3 and its phosphorylation in RES-mediated suppression of cervical cancer. The effects of RES on cervical cancer were determined by examining tumor tissues, their histological changes, and the volume and weight of tumor tissues grown from HeLa cells injected in female athymic BALB/C nude mice. The structure and target interaction of RES were virtually screened using the molecular docking program Autodock Vina. The status of phosphorylated STAT3, protein levels of epithelial-mesenchymal transition molecular markers and extracellular matrix degradation enzymes were determined through Western blot. We demonstrated that RES could suppress the proliferation and metastatic potential of cervical cancer cells by inactivating phosphorylation of STAT3 at Tyr705 but not Ser727. This effect was intensified by inhibition of the STAT3 signal pathway.

Guideline for diagnosis and treatment of spine trauma in the epidemic of COVID-19.

Outbreak of COVID-19 is ongoing all over the world. Spine trauma is one of the most common types of trauma and will probably be encountered during the fight against COVID-19 and resumption of work and production. Patients with unstable spine fractures or continuous deterioration of neurological function require emergency surgery. The COVID-19 epidemic has brought tremendous challenges to the diagnosis and treatment of such patients. To coordinate the diagnosis and treatment of infectious disease prevention and spine trauma so as to formulate a rigorous diagnosis and treatment plan and to reduce the disability and mortality of the disease, multidisciplinary collaboration is needed. This expert consensus is formulated in order to (1) prevent and control the epidemic, (2) diagnose and treat patients with spine trauma reasonably, and (3) reduce the risk of cross-infection between patients and medical personnel during the treatment.

The CXCR4/miR-125b/FoxP3 axis regulates the function of the epithelial barrier via autophagy in allergic rhinitis.

An impaired epithelial barrier is often observed in allergic rhinitis (AR), which facilitates the infiltration of allergens. The aim of this study was to investigate the role of autophagy in the impaired epithelial barrier in AR and the related signalling pathways. A human nasal epithelial cell line was treated with dust mite allergen (Derp1). Autophagy was evaluated by GFP-LC3 adenovirus transfection and measurement of autophagy-related proteins. Epithelial barrier function was evaluated by measuring tight junction protein expression, transepithelial electrical resistance, and fluorescein isothiocyanate-dextran (FD4) permeability. Next, miR-125b inhibitor, miR-125b mimics, shRNA targeting FoxP3, pcDNA3.1 expressing FoxP3, and inhibitor of C-X-C motif chemokine receptor type 4 (CXCR4) were used to investigate the roles of miR-125b, FoxP3, and CXCR4 in epithelial cell autophagy and epithelial barrier function. An in vivo AR model was generated by exposing rat nasal mucosa to an allergen. Derp1 exposure enhanced autophagy and impaired the epithelial barrier in epithelial cells. Upregulation of miR-125b expression led to enhanced autophagy and impaired epithelial barrier through inhibition of FoxP3. Derp1 exposure increased miR-125b expression by increasing the expression and activation of CXCR4, which downregulated FoxP3 expression and led to enhanced autophagy and an impaired epithelial barrier. In vivo analysis confirmed the role of the CXCR4/miR-125b/FoxP3 axis in the impaired epithelial barrier in AR. This study demonstrates that the CXCR4/miR-125b/FoxP3 axis may participate in the pathogenesis of AR by regulating autophagy in epithelial cells and dysfunction of the epithelial barrier.

Recommendations of protective measures for orthopedic surgeons during COVID-19 pandemic.

PURPOSE: It was the primary purpose of the present systematic review to identify the optimal protection measures during COVID-19 pandemic and provide guidance of protective measures for orthopedic surgeons. The secondary purpose was to report the protection experience of an orthopedic trauma center in Wuhan, China during the pandemic. METHODS: A systematic search of the PubMed, Cochrane, Web of Science, Google Scholar was performed for studies about COVID-19, fracture, trauma, orthopedic, healthcare workers, protection, telemedicine. The appropriate protective measures for orthopedic surgeons and patients were reviewed (on-site first aid, emergency room, operating room, isolation wards, general ward, etc.) during the entire diagnosis and treatment process of traumatic patients. RESULTS: Eighteen studies were included, and most studies (13/18) emphasized that orthopedic surgeons should pay attention to prevent cross-infection. Only four studies have reported in detail how orthopedic surgeons should be protected during surgery in the operating room. No detailed studies on multidisciplinary cooperation, strict protection, protection training, indications of emergency surgery, first aid on-site and protection in orthopedic wards were found. CONCLUSION: Strict protection at every step in the patient pathway is important to reduce the risk of cross-infection. Lessons learnt from our experience provide some recommendations of protective measures during the entire diagnosis and treatment process of traumatic patients and help others to manage orthopedic patients with COVID-19, to reduce the risk of cross-infection between patients and to protect healthcare workers during work. LEVEL OF EVIDENCE: IV.

Survey of COVID-19 Disease Among Orthopaedic Surgeons in Wuhan, People's Republic of China.

BACKGROUND: Coronavirus disease 2019 (COVID-19) broke out in Wuhan, the People's Republic of China, in December 2019 and now is a pandemic all around the world. Some orthopaedic surgeons in Wuhan were infected with COVID-19. METHODS: We conducted a survey to identify the orthopaedic surgeons who were infected with COVID-19 in Wuhan. A self-administered questionnaire was distributed to collect information such as social demographic variables, clinical manifestations, exposure history, awareness of the outbreak, infection control training provided by hospitals, and individual protection practices. To further explore the possible risk factors at the individual level, a 1:2 matched case-control study was conducted. RESULTS: A total of 26 orthopaedic surgeons from 8 hospitals in Wuhan were identified as having COVID-19. The incidence in each hospital varied from 1.5% to 20.7%. The onset of symptoms was from January 13 to February 5, 2020, and peaked on January 23, 8 days prior to the peak of the public epidemic. The suspected sites of exposure were general wards (79.2%), public places at the hospital (20.8%), operating rooms (12.5%), the intensive care unit (4.2%), and the outpatient clinic (4.2%). There was transmission from these doctors to others in 25% of cases, including to family members (20.8%), to colleagues (4.2%), to patients (4.2%), and to friends (4.2%). Participation in real-time training on prevention measures was found to have a protective effect against COVID-19 (odds ratio [OR], 0.12). Not wearing an N95 respirator was found to be a risk factor (OR, 5.20 [95% confidence interval (CI), 1.09 to 25.00]). Wearing respirators or masks all of the time was found to be protective (OR, 0.15). Severe fatigue was found to be a risk factor (OR, 4 [95% CI, 1 to 16]) for infection with COVID-19. CONCLUSIONS: Orthopaedic surgeons are at risk during the COVID-19 pandemic. Common places of work could be contaminated. Orthopaedic surgeons have to be more vigilant and take more precautions to avoid infection with COVID-19. LEVEL OF EVIDENCE: Diagnostic Level IV. See Instructions for Authors for a complete description of levels of evidence.

Epithelial cells expressed IL-33 to promote degranulation of mast cells through inhibition on ST2/PI3K/mTOR-mediated autophagy in allergic rhinitis.

Nasal epithelial cells are the first barrier against allergen infiltration in allergic rhinitis (AR), and the relationship between nasal epithelial cells and mast cell-mediated hypersensitivity remains unclear. This study aimed to investigate the possible association between allergen-challenged nasal epithelial cells (AR-HNEpC) and mast cell degranulation in AR. Our data revealed that calcium influx and degranulation were increased in AR-HNEpC-co-cultured mast cells. Expression of IL-33, a factor that binds to ST2 receptors on mast cells and regulates their degranulation, was elevated in AR-HNEpC. Blocking IL-33/ST2 pathway activated autophagy and inhibited degranulation and inflammatory factor release in mast cells. Furthermore, PI3K/mTOR was increased in IL-33-treated mast cells. Inhibition on PI3K/mTOR pathway enhanced autophagy and inhibited degranulation. Analysis using an in vivo AR model supported the above findings. In conclusion, IL-33 from epithelial cells promotes degranulation of mast cells in AR through inhibition on ST2/PI3K/mTOR-mediated autophagy, which provides a potential therapeutic target for the disease.Abbreviations: AR: allergic rhinitis; IL: interleukin; TNF-α: tumor necrosis factor-alpha; INF-γ: interferon-gamma; HNEpC: human nasal epithelial cell line; ATCC: American Type Culture Collection; C48/80: compound 48/80; 3-MA: 3-methyladenine; qPCR: quantitative PCR; AR-HNEpC: dust mite allergen-treated nasal epithelial cells; IgE: immunoglobulin E; Atg7: autophagy-related gene 7.