Multiplexed electrochemical nucleic acid sensor based on visible light-mediated metal-free thiol-yne click reaction for simultaneous detection of different nucleic acid targets.

Simultaneous detection of multiple tumor biomarkers with a simple and low-cost assay is crucial for early cancer detection and diagnosis. Herein, we presented a low-cost and simple assay for multiplexed detection of tumor biomarkers using a spatially separated electrodes strategy. The sensor is fabricated based on a metal-free thiol-yne click reaction, which is mediated by visible light, on commercially available indium tin oxide (ITO) electrodes. Four biomarkers, including p53 DNA, Brca2 DNA, K-ras DNA, and MicroRNA-204 RNA, were used as model analytes, and the corresponding oligonucleotide probes were modified on the desired electrode units sequentially with 530 nm irradiation light in the presence of photosensitizer Eosin Y. By this visible light-mediated coupling reaction, oligonucleotide probe densities of up to 9.2 ± 0.7 × 1010 molecules/cm2 were readily obtained on the ITO electrode surface. The proposed multiplexed E-NA sensor could detect four different nucleic acid targets concurrently without crosstalk among adjacent electrodes and was also successfully applied for detecting targets in a 20% fetal calf serum sample. The detection limits for p53 DNA, Brca2 DNA, K-ras DNA, and MicroRNA-204 RNA were 0.72 nM, 0.97 nM, 2.15 nM, and 1.73 nM, respectively. The developed approach not only has a great potential for developing cost-effective biosensors on affordable substrates for nucleic acid target detection, but also be easily extended to detect other targets by modifying the specific oligonucleotide probes anchored on the electrode.

Polysaccharides as a promising platform for the treatment of spinal cord injury: A review.

Spinal cord injury is incurable and often results in irreversible damage to motor function and autonomic sensory abilities. To enhance the effectiveness of therapeutic substances such as cells, growth factors, drugs, and nucleic acids for treating spinal cord injuries, as well as to reduce the toxic side effects of chemical reagents, polysaccharides have been gained attention due to their immunomodulatory properties and the biocompatibility and biodegradability of polysaccharide scaffolds. Polysaccharides hold potential as drug delivery systems in treating spinal cord injuries. This article aims to present an extensive evaluation of the potential applications of polysaccharide materials in scaffold construction, drug delivery, and immunomodulation over the past five years so that offering new directions and opportunities for the treatment of spinal cord injuries.

Tea leaf-derived exosome-like nanotherapeutics retard breast tumor growth by pro-apoptosis and microbiota modulation.

While several artificial nanodrugs have been approved for clinical treatment of breast tumor, their long-term applications are restricted by unsatisfactory therapeutic outcomes, side reactions and high costs. Conversely, edible plant-derived natural nanotherapeutics (NTs) are source-widespread and cost-effective, which have been shown remarkably effective in disease treatment. Herein, we extracted and purified exosome-like NTs from tea leaves (TLNTs), which had an average diameter of 166.9 nm and a negative-charged surface of - 28.8 mV. These TLNTs contained an adequate slew of functional components such as lipids, proteins and pharmacologically active molecules. In vitro studies indicated that TLNTs were effectively internalized by breast tumor cells (4T1 cells) and caused a 2.5-fold increase in the amount of intracellular reactive oxygen species (ROS) after incubation for 8 h. The high levels of ROS triggered mitochondrial damages and arrested cell cycles, resulting in the apoptosis of tumor cells. The mouse experiments revealed that TLNTs achieved good therapeutic effects against breast tumors regardless of intravenous injection and oral administration through direct pro-apoptosis and microbiota modulation. Strikingly, the intravenous injection of TLNTs, not oral administration, yielded obvious hepatorenal toxicity and immune activation. These findings collectively demonstrate that TLNTs can be developed as a promising oral therapeutic platform for the treatment of breast cancer.

Immune regulation and emerging roles of noncoding RNAs in Mycobacterium tuberculosis infection.

Tuberculosis, caused by Mycobacterium tuberculosis, engenders an onerous burden on public hygiene. Congenital and adaptive immunity in the human body act as robust defenses against the pathogens. However, in coevolution with humans, this microbe has gained multiple lines of mechanisms to circumvent the immune response to sustain its intracellular persistence and long-term survival inside a host. Moreover, emerging evidence has revealed that this stealthy bacterium can alter the expression of demic noncoding RNAs (ncRNAs), leading to dysregulated biological processes subsequently, which may be the rationale behind the pathogenesis of tuberculosis. Meanwhile, the differential accumulation in clinical samples endows them with the capacity to be indicators in the time of tuberculosis suffering. In this article, we reviewed the nearest insights into the impact of ncRNAs during Mycobacterium tuberculosis infection as realized via immune response modulation and their potential as biomarkers for the diagnosis, drug resistance identification, treatment evaluation, and adverse drug reaction prediction of tuberculosis, aiming to inspire novel and precise therapy development to combat this pathogen in the future.

Nanomedicines for Overcoming Cancer Drug Resistance.

Clinically, cancer drug resistance to chemotherapy, targeted therapy or immunotherapy remains the main impediment towards curative cancer therapy, which leads directly to treatment failure along with extended hospital stays, increased medical costs and high mortality. Therefore, increasing attention has been paid to nanotechnology-based delivery systems for overcoming drug resistance in cancer. In this respect, novel tumor-targeting nanomedicines offer fairly effective therapeutic strategies for surmounting the various limitations of chemotherapy, targeted therapy and immunotherapy, enabling more precise cancer treatment, more convenient monitoring of treatment agents, as well as surmounting cancer drug resistance, including multidrug resistance (MDR). Nanotechnology-based delivery systems, including liposomes, polymer micelles, nanoparticles (NPs), and DNA nanostructures, enable a large number of properly designed therapeutic nanomedicines. In this paper, we review the different mechanisms of cancer drug resistance to chemotherapy, targeted therapy and immunotherapy, and discuss the latest developments in nanomedicines for overcoming cancer drug resistance.

Near-Infrared-Enpowered Nanomotor-Mediated Targeted Chemotherapy and Mitochondrial Phototherapy to Boost Systematic Antitumor Immunity.

Phototherapy is an important strategy to inhibit tumor growth and activate antitumor immunity. However, the effect of photothermal/photodynamic therapy (PTT/PDT) is restricted by limited tumor penetration depth and unsatisfactory potentiation of antitumor immunity. Here, a near-infrared (NIR)-driven nanomotor is constructed with a mesoporous silicon nanoparticle (MSN) as the core, end-capped with Antheraea pernyi silk fibroin (ApSF) comprising arginine-glycine-aspartate (RGD) tripeptides. Upon NIR irradiation, the resulting ApSF-coated MSNs (DIMs) loading with photosensitizers (ICG derivatives, IDs) and chemotherapeutic drugs (doxorubicin, Dox) can efficiently penetrate into the internal tumor tissues and achieve effective phototherapy. Combined with chemotherapy, a triple-modal treatment (PTT, PDT, and chemotherapy) approach is developed to induce the immunogenic cell death of tumor cells and to accelerate the release of damage-associated molecular patterns. In vivo results suggest that DIMs can promote the maturation of dendritic cells and surge the number of infiltrated immune cells. Meanwhile, DIMs can polarize macrophages from M2 to M1 phenotypes and reduce the percentages of immunosuppressive Tregs, which reverse the immunosuppressive tumor microenvironment and activate systemic antitumor immunity. By achieving synergistic effects on the tumor inhibition and the antitumor immunity activation, DIMs show great promise as new nanoplatforms to treat metastatic breast cancer.

The role of interferons in ovarian cancer progression: Hinderer or promoter?

Ovarian cancer (OC) is a common gynecologic malignancy with poor prognosis and high mortality. Changes in the OC microenvironment are closely related to the genesis, invasion, metastasis, recurrence, and drug-resistance. The OC microenvironment is regulated by Interferons (IFNs) known as a type of important cytokines. IFNs have a bidirectional regulation for OC cells growth and survival. Meanwhile, IFNs positively regulate the recruitment, differentiation and activation of immune cells. This review summarizes the secretion and the role of IFNs. In particular, we mainly elucidate the actions played by IFNs in various types of therapy. IFNs assist radiotherapy, targeted therapy, immunotherapy and biotherapy for OC, except for some IFN pathways that may cause chemo-resistance. In addition, we present some advances in OC treatment with the help of IFN pathways. IFNs have the ability to powerfully modulate the tumor microenvironment and can potentially provide new combination strategies for OC treatment.

Multifunctional Mitochondria-Targeting Nanosystems for Enhanced Anticancer Efficacy.

Mitochondria, a kind of subcellular organelle, play crucial roles in cancer cells as an energy source and as a generator of reactive substrates, which concern the generation, proliferation, drug resistance, and other functions of cancer. Therefore, precise delivery of anticancer agents to mitochondria can be a novel strategy for enhanced cancer treatment. Mitochondria have a four-layer structure with a high negative potential, which thereby prevents many molecules from reaching the mitochondria. Luckily, the advances in nanosystems have provided enormous hope to overcome this challenge. These nanosystems include liposomes, nanoparticles, and nanomicelles. Here, we summarize the very latest developments in mitochondria-targeting nanomedicines in cancer treatment as well as focus on designing multifunctional mitochondria-targeting nanosystems based on the latest nanotechnology.

The landscape of immune checkpoint inhibitor therapy in advanced lung cancer.

BACKGROUND: The advent of immune checkpoint inhibitors (ICIs) therapy has resulted in significant survival benefits in patients with non-small-cell lung cancer (NSCLC) without increasing toxicity. However, the utilisation of immunotherapy for small-cell lung cancer (SCLC) remains unclear, with a scarcity of systematic comparisons of therapeutic effects and safety of immunotherapy in these two major lung cancer subtypes. Herein, we aimed to provide a comprehensive landscape of immunotherapy and systematically review its specific efficacy and safety in advanced lung cancer, accounting for histological types. METHODS: We identified studies assessing immunotherapy for lung cancer with predefined endpoints, including overall survival (OS), progression-free survival (PFS), objective response rate (ORR), and treatment-related adverse events (TRAE), from PubMed, Embase, Medline, and Cochrane library. A random-effects or fixed-effect model was adopted according to different settings. RESULTS: Overall, 38 trials with 20,173 patients with lung cancer were included in this study. ICI therapy resulted in a significantly prolonged survival in both patients with NSCLC and SCLC when compared with chemotherapy (hazard ratio [HR] = 0.74; 95% confidence interval [CI], 0.70-0.79] and [HR = 0.82; 95% CI, 0.75-0.90], respectively). The magnitude of disease control and survival benefits appeared superior with ICI plus standard of care (SOC) when compared with SOC alone. OS and PFS advantages were observed only when immunotherapy was employed as the first-line treatment in patients with SCLC. CONCLUSION: ICI therapy is a promising therapeutic option in patients with NSCLC and SCLC. ICI plus SOC can be recommended as the optimal first-line treatment for patients with SCLC, and double-target ICIs combined with SOC are recommended in patients with NSCLC as both the first and subsequent lines of treatment. Additionally, non-first-line immunotherapy is not recommended in patients with SCLC.

A meta-analysis of randomized controlled trials of a traditional Chinese medicine prescription, modified RunChang-Tang, in treating functional constipation.

BACKGROUND: Modified Runchang-Tang (MRCT), a Chinese herbal medicine, is widely used to treat functional constipation (FC), which is a common digestive system disease. However, its efficacy has not been evaluated systematically and objectively. Thus, a meta-analysis was conducted to assess the efficacy and safety of MRCT for treating functional constipation. METHODS: We searched for relevant publications from Embase, Medline, The Cochrane Library, Chinese Biomedical Literature Database, China National Knowledge Infrastructure, Chinese Scientific Journals Database, and Wanfang Data for relevant literature. The timeframe of retrieval was set from the founding date of each database to July 15, 2020. RESULT: A total of 26 randomized controlled trials with 2103 individuals were included in this meta-analysis. All trials were conducted in mainland China and were written in Chinese. The results showed that MRCT monotherapy provided better symptom relief in FC patients compared to prokinetic agent monotherapy (odds ratio, [OR] = 4.06), osmotic laxatives (OR = 4.39) and stimulant laxatives (OR = 2.99). Additionally, there were no obvious adverse effects in MRCT group compared with control group. CONCLUSION: MRCT treatment is an efficient and safe treatment for FC. However, considering the limitations of this study, further well-designed randomized controlled trials are required to validate this conclusion.

Full-Endoscopic Decompression with the Application of an Endoscopic-Matched Ultrasonic Osteotome for Removal of Ossification of the Thoracic Ligamentum Flavum.

BACKGROUND: Resection of the ossification of the thoracic ligamentum flavum (OTLF) with a high-speed burr may cause a high rate of perioperative complications, such as dural laceration and/or iatrogenic spinal cord injury. OBJECTIVES: The aim of this study was to investigate the safety and feasibility of the endoscopic-matched ultrasonic osteotome in full-endoscopic spinal surgery for direct removal of OTLF. STUDY DESIGN: Retrospective study. SETTING: All data were from Honghui Hospital in Xi'an. METHODS: This study conducted between December 2017 and December 2018, included 27 consecutive patients who met the study criteria, had single-level OTLF, and underwent full-endoscopic decompression under local anesthesia. The postoperative follow-up was scheduled at 1, 3, 6, and 12 months postoperatively. Outcomes evaluations included the Visual Analog Scale (VAS) score for lower extremity pain and the modified Japanese Orthopaedic Association (mJOA) score and improvement rate for the assessment of thoracic myelopathy. Removal of OTLF was measured by comparing the pre- and postoperative computed tomography (CT) and magnetic resonance imaging (MRI) scans. RESULTS: The operation was completed in all patients without conversion to open surgery. The operation time ranged from 65 to 125 minutes (average, 83.7 ± 12.3 minutes). All patients were followed up for 12 to 18 months, with an average follow-up of 14.3 ± 1.3 months. Satisfactory neurologic decompression was confirmed by postoperative CT and MRI, and no revision surgery was required. The VAS and mJOA scores showed statistically higher improvement at the 1-month follow-up and the last follow-up compared with the preoperative assessment (P < 0.05). According to the improvement rate at the final follow-up, 20 cases were classified as good, 6 cases were fair, and 1 case remained unchanged. LIMITATIONS: A single-center, noncontrol study. CONCLUSIONS: The endoscopic-matched ultrasonic osteotome can be considered quite safe and feasible for direct removal of OTLF during full-endoscopic spinal surgery in strictly selected patients, as this allows for effective direct decompression of OTLF while minimizing trauma and instability. In addition, because of the design characteristics of the ultrasonic osteotome, surgical complications, especially dural tears and spinal cord injury, can also be effectively controlled.

Can Additional Facet Joint Block Improve the Clinical Outcome of Kyphoplasty for Acute Osteoporotic Vertebral Compression Fractures?

BACKGROUND: Percutaneous kyphoplasty (PKP) has been reported to provide a favorable analgesic effect for pain caused by osteoporotic vertebral compression fractures (OVCFs). However, a systematic review demonstrated that pain relief was only reported for approximately 86% of kyphoplasty treatments. OBJECTIVES: To explore whether an additional facet joint block (FJB) can minimize pain and improve the clinical outcome of PKP in patients with acute OVCFs. STUDY DESIGN: Prospective study. SETTING: All data were from Honghui Hospital in Xi'an. METHODS: According to the inclusion and exclusion criteria, 194 patients were eventually included in our study; they were randomly divided into 2 groups of 97 patients each and treated with either PKP + FJB or PKP alone. Follow-up consultations were scheduled 1 day, 3 days, 1 week, 1 month, 3 months, and 1 year postoperatively; the demographic characteristics, related surgical information, and complications observed within both groups were recorded. The clinical evaluation parameters included the intraoperative satisfaction score, the Visual Analog Scale (VAS) score, and the Oswestry Disability Index (ODI). RESULTS: A total of 171 patients (61 men and 110 women; age range: 62-85 years) completed the full postoperative follow-up schedule, with 83 patients in the PKP + FJB group and 88 in the PKP group. No significant differences were observed in the genders, ages, preoperative bone mineral density, surgical levels, or volume of cement injected between the 2 groups (P > 0.05, respectively). The average duration of the surgeries in the PKP + FJB group was slightly longer than that in the PKP group (35.5 ± 4.8 min vs. 31.8 ± 4.3 min; P = 0.038), and in terms of the clinical outcomes, the average intraoperative satisfaction score was significantly higher in the PKP + FJB group (8.6 ± 1.1 vs. 6.3 ± 1.3; P < 0.001). Compared with the preoperative data, significant improvements in the VAS scores of back pain and ODI were observed at each follow-up interval (P < 0.05, respectively). These scores were significantly higher in the PKP + FJB group than in the PKP group; however, this was only observed within the first month after the procedure. LIMITATIONS: A single-center noncontrol study. CONCLUSIONS: The addition of an FJB (which in our study involved a unique combination of ropivacaine, prednisolone, and vitamin B12) improved the short-term clinical outcome of PKP for acute OVCFs. The local anti-inflammatory and analgesic effects on the facet joints resulted in higher intraoperative satisfaction and lower VAS and ODI scores for the first postoperative month when compared with the PKP group.

The therapeutic effect and safety of the drugs for COVID-19: A systematic review and meta-analysis.

BACKGROUND: Coronavirus disease 2019 (COVID-19) has spread almost all regions of the world and caused great loss to the whole body of mankind. Thus, numerous clinical trials were conducted to find specific medicine for COVID-19 recently. However, it remains unanswered whether they are beneficial. OBJECTIVE: This study aimed to evaluate the efficiency and safety of the COVID-19 medicine. METHODS: Studies were determined through searching PubMed, Embase, Cochrane Library, and Medline. The studies of COVID-19 medicine were involved with eligible end points containing mortality, discharge rate, rate of clinical improvement, and rate of serious adverse events. RESULTS: A total of 33 studies involving 37,879 patients were included in our study, whose intervening measures contained three major types of COVID-19 medicine, ACEI/ARB, antiviral medicine, and chloroquine/hydroxychloroquine. Compared to control group, COVID-19 drugs have no distinct effect on mortality (RR, 0.93; 95% CI, 0.79-1.11, P = .43) and discharge rate (RR, 1.06; 95% CI, 0.98-1.14, P = .13). However, antiviral medicine presents the obvious advantage in clinical improvement (RR, 1.11; 95% CI, 1.01-1.23, P < .05). In addition, the serious adverse events rate (RR, 0.75; 95% CI, 0.63-0.88, P < .05) of COVID-19 medicine is lower than control group. CONCLUSION: The results indicated antiviral medicine was potential specific medicine for COVID-19 treatment by improving clinical symptoms, but it failed to increase the discharge rate and reduce mortality. Chloroquine/hydroxychloroquine and ACEI/ARB had no significant effect on treatment of COVID-19, thus they were not recommended for routine medication. Moreover, more trials are needed to find effective drugs to lower the mortality of COVID-19 patients.

Spinal Epidural Hematoma After Percutaneous Kyphoplasty: Case Report and Literature Review.

OBJECTIVE: To present the case of a patient on long-term anticoagulants who developed acute spinal epidural hematoma (SEH) after percutaneous kyphoplasty (PKP) without signs of major cement extravasation to the spinal canal. METHODS: A 64-year-old woman with long-term oral antiplatelet drugs underwent the L1 PKP. Immediately after the operation, the back pain improved significantly without neurological deficit. However, 12 hours later, she developed progressive weakness of the bilateral lower limbs. No intraspinal cement leakage was obvious on the postoperative lumbar radiograph and computed tomography. RESULTS: An emergency MRI examination revealed a high signal aggregation in front of the spinal cord from T12 to L1, indicating spinal cord compression. The SEH was verified and removed during the laminectomy from T12-L1. Following the decompression surgery, the neurological deficit of the lower limbs improved. On follow-up after 6 months, the muscle strength of the bilateral lower limbs had returned to normal. CONCLUSION: For the patient with long-term oral antiplatelet drugs or coagulation malfunction, the transpedicle approach or that via the costovertebral joint with a smaller abduction angle is recommended to reduce the risk of injury to the inner wall of the pedicle. For progressive aggravation of neurological dysfunction after surgery, SEH formation should be suspected despite the absence of intraspinal bone cement leakage. Secondary emergency decompression should be considered to avoid permanent damage to spinal cord nerve function caused by continuous compression.

Gradient local anesthesia for percutaneous endoscopic interlaminar discectomy at the L5/S1 level: a feasibility study.

BACKGROUND: During the process of shearing the ligamentum flavum, rotating the working channel, and manipulating the annulus fibrosis, the sinuvertebral nerve and the spinal nerve root can be irritated, inducing intolerable back and leg pain. Thus, general anesthesia is recommended and well accepted by most surgeons when performing percutaneous endoscopic lumbar discectomy (PELD) via the interlaminar approach. The aim of our study was to explore the efficacy and safety of percutaneous endoscopy interlaminar lumbar discectomy with gradient local anesthesia (LA) in patients with L5/S1 disc herniation. METHODS: This retrospective study was conducted between December 2017 and June 2018. The study included 50 consecutive patients who met the study criteria, had single-level L5/S1 disc herniation, and underwent PELD via the interlaminar approach under gradient LA. Different concentrations of local anesthetic compound (LAC) were injected into different tissues inside and outside the ligamentum flavum to complete gradient LA. The evaluation criteria included the intraoperative satisfaction score, visual analog scale (VAS) score, Oswestry Disability Index (ODI), complications, and adverse reactions. RESULTS: The intraoperative satisfaction score was consistently over 7, with an average score of 9.3 ± 0.7, indicating that LAC can achieve satisfactory pain control throughout the PELD operation without additional anesthesia. The postoperative VAS score and ODI were dramatically improved at each follow-up interval (P < 0.001, respectively). There was no serious complication such as dural rupture caused by puncture, dural laceration caused by manipulation under endoscopy, total spinal anesthesia, iatrogenic nerve root injury, epidural hematoma, infections, or local anesthetic-related adverse reactions. Three patients experienced transient postoperative dysesthesia of the lower limbs that gradually recovered within 24 h. CONCLUSIONS: Gradient local anesthesia can satisfactorily and safely control intraoperative pain during the PELD via the interlaminar approach. It can not only improve intraoperative satisfaction, but also reduce local anesthesia-related adverse reactions and surgery-related complications.

Comparison of Clinical and Radiologic Outcome Between Mini-Open Wiltse Approach and Fluoroscopic-Guided Percutaneous Pedicle Screw Placement: A Randomized Controlled Trial.

OBJECTIVE: To compare clinical efficacy, radiographic outcome, and radiation exposure between mini-open pedicle screw (MPS) fixation with the Wiltse approach and percutaneous pedicle screw (PPS) fixation in treatment of young and middle-aged patients with thoracolumbar burst fractures. METHODS: Of 60 patients with thoracolumbar vertebrae fractures treated in our hospital from January 2017 to January 2018, 30 were randomly assigned to the MPS group and 30 were randomly assigned to the PPS group. Clinical efficacy, radiographic outcome, and radiation exposure were compared between the 2 groups. RESULTS: The average age of patients was 42.2 ± 6.7 years in the MPS group and 43.0 ± 6.9 years in the PPS group (P = 0.668). There was no significant difference between the 2 groups in blood loss, hospital stay, postoperative visual analog scale score for back pain, and Oswestry Disability Index score. The vertebral body height and vertebral body angle of the MPS group were significantly better than those of the PPS group at the last follow-up. There was no significant difference in the accuracy rate of pedicle screw placement between the MPS group and the PPS group; the facet joint violation was significantly higher in the PPS group. The average radiation exposure dosage was lower in the MPS group. CONCLUSIONS: Both MPS fixation with the Wiltse approach and PPS fixation are safe and effective in the treatment of single-segment thoracolumbar vertebral fractures. Nevertheless, considering the surgical duration, radiation exposure, facet joint violation, vertebral body height, and vertebral body angle at the last follow-up, MPS fixation with the Wiltse approach is a better choice than PPS.

The analgesic effect of tramadol combined with butorphanol on uterine cramping pain after repeat caesarean section: a randomized, controlled, double-blind study.

PURPOSE: This study aimed to explore the effect of patient-controlled intravenous analgesia (PCIA) using tramadol combined with butorphanol on uterine cramping pain in women undergoing repeat caesarean section. METHODS: A total of 126 patients, who were scheduled to undergo repeat caesarean section under spinal anesthesia, were included. PCIA using tramadol combined with butorphanol or sufentanil was randomly performed for postoperative pain control. Postoperative uterine cramping pain and wound pain within 48 h after surgery were evaluated. Postoperative analgesic consumption, early activity time, and length of hospital stay were also recorded and analyzed. RESULTS: Uterine cramping pain intensity in women undergoing repeat caesarean section was significantly higher compared with their wound pain (P < 0.05). The mean visual analog scale (VAS) score for uterine cramping pain in the tramadol-butorphanol group was significantly lower than that in the sufentanil group at rest, and at 6 h and 12 h after surgery. VAS scores for uterine cramping pain during movement at 6 h, 12 h, and 24 h after surgery in the tramadol-butorphanol group were also significantly lower than that in sufentanil group (P < 0.05). There was no significant difference in VAS score for wound pain at the different time points between the tramadol-butorphanol and sufentanil groups (P > 0.05). Patient-controlled intravenous analgesia with tramadol accelerated early rehabilitation and decreased the length of hospital stay (P < 0.05). CONCLUSION: PCIA using tramadol combined with butorphanol provided a better analgesic effect and accelerated postoperative rehabilitation compared with sufentanil, and may be an optimal analgesic strategy for women undergoing repeat caesarean section. CLINICAL TRIAL REGISTRATION: The trial was registered at Chinese Clinical Trial Registry ( www.chictr.org.cn ) with ID: ChiCTR-1800014986.

Primary radical hysterectomy vs chemoradiation for IB2-IIA cervical cancer: A systematic review and meta-analysis.

BACKGROUND: To compare the clinical outcomes of radical hysterectomy (RH) with chemoradiotherapy (CRT) in women with stage IB2-IIA cervical cancer. METHODS: Based on articles published up to December 2017, a literature search of PubMed, Embase, the Cochrane Central Register of Controlled Trials (CENTRAL), and Chinese National Knowledge Infrastructure (CNKI) databases was conducted to identify eligible studies. Overall survival (OS), progression-free survival (PFS) with hazard ratios (HRs), and toxicities with odds ratios (ORs) were analyzed. RESULTS: In total, 7 studies comprising 687 patients were identified for this meta-analysis. RH showed a significant trend toward improved survival outcomes compared with those of CRT, regardless of OS (HR = 0.49, 95% confidence interval [CI] 0.36-0.67, P < .001); or PFS (1.61, 95% CI 1.15-2.26, P = .005) for IB2-IIA cervical cancer. Subgroup analysis revealed that stage IB2 cervical cancer patients obtained better OS (HR = 0.36, 95% CI 0.23-0.56, P < .001; heterogeneity: P = .32, I = 13%). However, a higher incidence of grade 3/4 genitourinary abnormalities was evident with RH (OR = 2.3, 95% CI 1.42-3.87, P = .021). CONCLUSION: Our study suggested that RH had distinct advantages over CRT for carcinoma of the uterine cervix with FIGO stage IB2-IIA, especially for IB2 cervical cancer.

Inflammation-dependent overexpression of c-Myc enhances CRL4DCAF4 E3 ligase activity and promotes ubiquitination of ST7 in colitis-associated cancer.

Inflammation is well known as an important driver of the initiation of colitis-associated cancer (CAC). Some cytokines, such as IL-6 and TNF-α can activate expression of the oncogene c-Myc (MYC) and regulate its downstream effects. Cullin-RING E3 Ligases (CRLs) are emerging as master regulators controlling tumorigenesis. Here, we demonstrate that two cullin genes, CUL4A and CUL4B, but not other members, are specifically overexpressed in CAC tumour samples and positively correlate with levels of the proinflammatory cytokines IL-1ß and IL-6. In vitro experiments revealed that the transcription factor c-Myc can specifically activate the expression of CUL4A and CUL4B by binding to a conserved site (CACGTG) located in their promoters. Additionally, we found that both CUL4A and CUL4B can form an E3 complex with DNA damage-binding protein 1 (DDB1) and DDB1-CUL4-associated factor 4 (DCAF4). In vitro and in vivo ubiquitination analyses indicate that CRL4DCAF4 E3 ligase specifically directs degradation of ST7 (suppression of tumorigenicity 7). Overexpression of c-Myc in human colon epithelial cells resulted in the accumulation of CUL4A, CUL4B and DCAF4, but degradation of ST7. In contrast, knockdown of c-Myc, CUL4A or CUL4B in the colon adenocarcinoma cell line HT29 caused accumulation of ST7 and inhibition of cell proliferation, colony formation ability and in vivo tumour growth. Collectively, our results provide in vitro and in vivo evidence that c-Myc regulates CRL4DCAF4 E3 ligase activity to mediate ubiquitination of ST7, whose presence is physiologically essential for CAC tumorigenesis. © 2019 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Supramolecular Gel Based on Crown-Ether-Appended Dynamic Covalent Macrocycles.

A new type of dynamic covalent macrocycle with self-promoted supramolecular gelation behavior is developed. Under oxidative conditions, the dithiol compound containing a diamide alkyl linker with an odd number (7) of carbon chain and an appended crown ether shows a remarkable gelation ability in acetonitrile, without any template molecules. Due to the existence of crown ethers and disulfide bonds, the obtained gel shows a multiple stimuli-responsiveness behavior. The mechanical properties and reversibility of the gel are investigated. Computational modeling suggests that the peripheral chain for diamide hydrogen bonding is responsible for the gelation process.