Molecular Insight into CO2 Improving Oil Mobility in Shale Inorganic Nanopores Containing Water Films.

CO2 injection into shale reservoirs has been recognized as one of the most promising techniques for enhanced oil recovery and carbon capture, utilization, and storage. However, the omnipresent nanopores and the water films formed near the pore walls affect the understanding of mechanisms of CO2 regulating crude oil mobility in shale nanopores. In this work, we employ molecular dynamics simulations to study the occurrence and flow of CO2 and octane (nC8) mixtures in quartz nanopores containing water films, to illustrate the impact mechanisms of CO2 on nC8 mobility. The results indicate that nC8 exists between water films, and CO2 is mainly miscible with nC8 in the pore center, and a small portion of it accumulates at the interface between nC8 and the water film. CO2 significantly decreases the apparent viscosity of nC8 in both the bulk nC8 region and the nC8-water interface region, improving nC8 fluidity. As the percentage of CO2 in the CO2 and nC8 mixtures increases from 0 to 50%, the mean flow velocities of nC8 in the bulk phase region and the nC8-water interface region increase by 92.85 and 60.64%, respectively. Three major microscopic mechanisms of CO2 improving nC8 fluidity in quartz nanopores with water films are summarized: (i) CO2 reduces friction between nC8 and the water film by increasing the angle between nC8 molecules and the plane of the water film; (ii) CO2 widens the distance between nC8 molecules, causing the volume expansion of nC8 and its viscosity reduction; (iii) CO2 significantly increases the most probable and average velocities of nC8 molecules, thus improving their mobility. Our results enhance the comprehension of how CO2 facilitates oil flow in water-bearing shale reservoirs and the exploitation of unconventional oil resources.

[Two children with late-onset congenital central hypoventilation syndrome].

Two children with late-onset congenital central hypoventilation syndrome were reported, one of whom was male and had no abnormal manifestations after birth, respiratory failure occurs at the age of 1 year and 6 months. After being hospitalized, he was treated with oxygen inhalation and non-invasive ventilation, but carbon dioxide retention could not be corrected. After one month of tracheal intubation, he was failure to wean from ventilator, so tracheostomy was performed. He needs a ventilator to help breath while sleeping, and can breath autonomously during the day without ventilator. The other case was a female, with no abnormalities after birth. At the age of 11 months, she developed respiratory failure. During sleep, the child needs non-invasive assisted ventilation through a nasal mask, and during the day, she breathed autonomously.Two patients were followed up forever 2 years and their growth and development were normal.

Ultrasound-guided transforaminal epidural injection with fluoroscopy confirmation for the treatment of unilateral lumbar radiculopathy: A randomized controlled non-inferiority study.

BACKGROUND: Ultrasound (US)-guided injections for chronic pain has multiple advantages over traditional radiologic method. The study was performed to exam the clinical outcomes of lumbar transforaminal epidural injection (LTFEI) between US and fluoroscopy (FL) guidance for lumbar radiculopathy (LRP). METHODS: A total of 164 patients with LRP were randomly assigned into US and FL group to receive LTFEI in a 1:1 ratio. Pain relief and functional disability were assessed by numeric rating scale (NRS) and Modified Oswestry Disability Questionnaire (MODQ) scores before treatment, 1 month and 3 months post-intervention. Contrast spread pattern, fluoroscopic image number and complications were also recorded. The primary outcome was accurate rate of contrast dispersing into lumbar epidural space, and non-inferiority margin was predefined at -15 %. RESULTS: The accuracy of LTFEI was 90.2 % and 91.5 % in US and FL group, and the lower limit of the 95 %CI of mean difference between two modalities (-4.9 % (95 %CI: -12.8 %, 3.1 %)) was above the non-inferiority margin. Procedure time in US group (531.90 ± 67.12 s) was shorter than FL group (904.20 ± 120.20 s) (p < 0.05), while radiation dosage in the US group was lower than in the FL group (3047.20 ± 569.53 vs. 8807.50 ± 1039.10 µGy m2, p < 0.001). Both groups didn't differ in pain reduction (F = 1.050, p = 0.306) and functional improvement (F = 0.103, p = 0.749) during follow-up period. No severe complications occurred in both groups. CONCLUSIONS: US-guided LTFEI confirmed by FL was not inferior to conventional FL method in terms of accurate rate of lumbar epidural contrast dispersion. Effective pain relief and functional ability improvement were comparable between two modalities, and US technique had advantages of less radiation exposure and possible facilitation of avoiding critical vessels around intervertebral foramen.

An updated patent review of IDO1 inhibitors for cancer (2018-2022).

INTRODUCTION: Indoleamine 2,3-dioxygenase 1 (IDO1) is highly related to the immune evasion of a wide range of malignancies due to its role in the immune suppression caused by the depletion of tryptophan (Trp) and the accumulation of kynurenine (Kyn). The combination of IDO1 inhibitors with other treatments represents a promising strategy in immunotherapy, although considerable challenges lie ahead. AREAS COVERED: This review focuses on patent publications searched from Espacenet and Google Scholar, and related to IDO1 inhibitors with potential anti-cancer utilization during the period 2018-2022. EXPERT OPINION: Despite the clinical trial failure of the first-in-class IDO1 inhibitor epacadostat in combination with pembrolizumab, numerous studies have been carried on to pursue more efficient IDO1-based immune-modulating therapeutic solutions. A large number of IDO1 inhibitors with new structures and design concepts have been produced with the impetus of crystallographic studies, and have shown great research potential. The elaboration on the combination of IDO1 inhibitors with other targeting agents, the more precise selection of patients, the identification of more reliable biomarkers for evaluating the IDO1 treatment, and the investigation of possible toxicity, are critical factors to promote IDO1-based immunotherapies from bench to bedside.

[Preliminary study on efficacy and safety of submucosal plasma ablation of inferior turbinate in children with allergic rhinitis complicated with obstructive sleep apnea syndrome].

Objective:This study aimed to investigate the long-term clinical efficacy and safety of inferior turbinate submucosal plasma ablation combined with or without tonsillar and adenoid surgery in children with allergic rhinitis（AR） combined with obstructive sleep apnea syndrome（OSAS） who were ineffective after conservative systemic treatment. Methods:A total of 43 children with AR complicated with OSAS who met the inclusion criteria among 68 children hospitalized from January 2019 to February 2022 were retrospectively analyzed. The data were collected, including the clinical characteristics, surgical methods perioperative management and prevention and treatment of complications. Moreover, one year follow-up was performed to compare the VAS scores of children before and after surgery, and to evaluate their mid-term and long-term outcomes. Results:The average operation time was 36 minutes, meanwhile, the intraoperative blood was limited. The symptoms of nasal congestion, runny nose, sleep snoring, and mouth breathing were significantly improved after operation, and the results were satisfactory after one-year follow-up without complications such as bleeding, hematoma, intraoperative adhesion, and nasal dryness. Conclusion:Submucosal plasma ablation of inferior turbinate with or without tonsillectomy adenoidectomy in children with AR can effectively improve the clinical symptoms of AR combined with OSAS children who are ineffective after conservative treatment. It can improve the symptoms of sleep-disordered breathing such as sleep snoring and mouth breathing, with good mid-and long-term curative effects and fewer complications, which is an effective and safe treatment for children with AR combined with OSAS.

[Application of multimodal combined surgical strategy in children with intractable laryngeal airway obstruction].

Objective:To explore the selection of surgical methods and intraoperative strategies for the treatment of children with intractable laryngeal airway obstruction, and to provide new options for the diagnosis and treatment of children with intractable laryngeal airway obstruction. Methods:The clinical data of 12 children with intractable laryngeal airway obstruction treated by our team from January 2005 to December 2021 were retrospective analyzed. All the children were treated with minimally invasive surgery under rigid bronchoscope or suspension laryngoscope combined with electronic endoscope. The surgical methods included laryngeal microsurgery, plasma ablation, balloon dilatation, drug-eluting stents, laser ablation, endoscopic snare, etc. The patients were followed up after operation. Results:All patients completed the operation under general anesthesia, and there were no intraoperative or postoperative complications. Except for one patient with bilateral vocal cord paralysis who failed to extubation due to restenosis, the others were successfully extubated after operation. Among them, 9 cases of benign space-occupying obstruction were followed up for 5-60 months without recurrence, and 2 cases of malignant tumor-induced obstruction were followed up for 24 months（acinar cell carcinoma） and 36 months（mucoepidermoid carcinoma） without recurrence. Conclusion:Endoscopic multi-operation is effective for children with intractable obstruction. Compared with traditional thoracotomy, endoscopic multi-operation strategies has the advantages of less trauma, faster and safer. For different sizes, locations and pathological types of obstruction, different surgical equipment and methods should be combined.

Modified Spared Nerve Injury Surgery Model of Neuropathic Pain in Mice.

Spared nerve injury (SNI) is an animal model that mimics the cardinal symptoms of peripheral nerve injury for studying the molecular and cellular mechanism of neuropathic pain in mice and rats. Currently, there are two types of SNI model, one to cut and ligate the common peroneal and the tibial nerves with intact sural nerve, which is defined as SNIs in this study, and another to cut and ligate the common peroneal and the sural nerves with intact tibial nerve, which is defined as SNIt in this study. Because the sural nerve is purely sensory whereas the tibial nerve contains both motor and sensory fibers, the SNIt model has much less motor deficit than the SNIs model. In the traditional SNIt mouse model, the common peroneal and the sural nerves are cut and ligated separately. Here a modified SNIt surgery method is described to damage both common peroneal and sural nerves with only one ligation and one cut with a shorter procedure time, which is easier to perform and reduces the potential risk of stretching the sciatic or tibial nerves, and produces similar mechanical hypersensitivity as the traditional SNIt model.

Hydromorphone for cancer pain.

BACKGROUND: This is an update of the original Cochrane Review first published in Issue 10, 2016. For people with advanced cancer, the prevalence of pain can be as high as 90%. Cancer pain is a distressing symptom that tends to worsen as the disease progresses. Evidence suggests that opioid pharmacotherapy is the most effective of these therapies. Hydromorphone appears to be an alternative opioid analgesic which may help relieve these symptoms. OBJECTIVES: To determine the analgesic efficacy of hydromorphone in relieving cancer pain, as well as the incidence and severity of any adverse events. SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase and clinical trials registers in November 2020. We applied no language, document type or publication status limitations to the search. SELECTION CRITERIA: We included randomised controlled trials (RCTs) that compared hydromorphone with placebo, an alternative opioid or another active control, for cancer pain in adults and children. Primary outcomes were participant-reported pain intensity and pain relief; secondary outcomes were specific adverse events, serious adverse events, quality of life, leaving the study early and death. DATA COLLECTION AND ANALYSIS: Two review authors independently extracted data. We calculated risk ratio (RR) and 95% confidence intervals (CI) for binary outcomes on an intention-to-treat (ITT) basis. We estimated mean difference (MD) between groups and 95% CI for continuous data. We used a random-effects model and assessed risk of bias for all included studies. We assessed the evidence using GRADE and created three summary of findings tables. MAIN RESULTS: With four new identified studies, the review includes a total of eight studies (1283 participants, with data for 1181 participants available for analysis), which compared hydromorphone with oxycodone (four studies), morphine (three studies) or fentanyl (one study). All studies included adults with cancer pain, mean age ranged around 53 to 59 years and the proportion of men ranged from 42% to 67.4%. We judged all the studies at high risk of bias overall because they had at least one domain with high risk of bias. We found no studies including children. We did not complete a meta-analysis for the primary outcome of pain intensity due to skewed data and different comparators investigated across the studies (oxycodone, morphine and fentanyl). Comparison 1: hydromorphone compared with placebo We identified no studies comparing hydromorphone with placebo. Comparison 2: hydromorphone compared with oxycodone Participant-reported pain intensity We found no clear evidence of a difference in pain intensity (measured using a visual analogue scale (VAS)) in people treated with hydromorphone compared with those treated with oxycodone, but the evidence is very uncertain (3 RCTs, 381 participants, very low-certainty evidence). Participant-reported pain relief We found no studies reporting participant-reported pain relief. Specific adverse events We found no clear evidence of a difference in nausea (RR 1.13 95% CI 0.74 to 1.73; 3 RCTs, 622 participants), vomiting (RR 1.18, 95% CI 0.72 to 1.94; 3 RCTs, 622 participants), dizziness (RR 0.91, 95% CI 0.58 to 1.44; 2 RCTs, 441 participants) and constipation (RR 0.92, 95% CI 0.72 to 1.19; 622 participants) (all very low-certainty evidence) in people treated with hydromorphone compared with those treated with oxycodone, but the evidence is very uncertain. Quality of life We found no studies reporting quality of life. Comparison 3: hydromorphone compared with morphine Participant-reported pain intensity We found no clear evidence of a difference in pain intensity (measured using the Brief Pain Inventory (BPI) or VAS)) in people treated with hydromorphone compared with those treated with morphine, but the evidence is very uncertain (2 RCTs, 433 participants; very low-certainty evidence). Participant-reported pain relief We found no clear evidence of a difference in the number of clinically improved participants, defined by 50% or greater pain relief rate, in the hydromorphone group compared with the morphine group, but the evidence is very uncertain (RR 0.99, 95% CI 0.84 to 1.18; 1 RCT, 233 participants; very low-certainty evidence). Specific adverse events At 24 days of treatment, morphine may reduce constipation compared with hydromorphone, but the evidence is very uncertain (RR 1.56, 95% CI 1.12 to 2.17; 1 RCT, 200 participants; very low-certainty evidence). We found no clear evidence of a difference in nausea (RR 0.94, 95% CI 0.66 to 1.30; 1 RCT, 200 participants), vomiting (RR 0.87, 95% CI 0.58 to 1.31; 1 RCT, 200 participants) and dizziness (RR 1.15, 95% CI 0.71 to 1.88; 1 RCT, 200 participants) (all very low-certainty evidence) in people treated with hydromorphone compared with those treated with morphine, but the evidence is very uncertain. Quality of life We found no studies reporting quality of life. Comparison 4: hydromorphone compared with fentanyl Participant-reported pain intensity We found no clear evidence of a difference in pain intensity (measured by numerical rating scale (NRS)) at 60 minutes in people treated with hydromorphone compared with those treated with fentanyl, but the evidence is very uncertain (1 RCT, 82 participants; very low-certainty evidence). Participant-reported pain relief We found no studies reporting participant-reported pain relief. Specific adverse events We found no studies reporting specific adverse events. Quality of life We found no studies reporting quality of life. AUTHORS' CONCLUSIONS: The evidence of the benefits and harms of hydromorphone compared with other analgesics is very uncertain. The studies reported some adverse events, such as nausea, vomiting, dizziness and constipation, but generally there was no clear evidence of a difference between hydromorphone and morphine, oxycodone or fentanyl for this outcome. There is insufficient evidence to support or refute the use of hydromorphone for cancer pain in comparison with other analgesics on the reported outcomes. Further research with larger sample sizes and more comprehensive outcome data collection is required.

A Personalized Mass Spectrometry-Based Assay to Monitor M-Protein in Patients with Multiple Myeloma (EasyM).

PURPOSE: M-protein is a well-established biomarker used for multiple myeloma monitoring. Current improvements in multiple myeloma treatment created the need to monitor minimal residual disease (MRD) with high sensitivity. Measuring residual levels of M-protein in serum by MS was established as a sensitive assay for disease monitoring. In this study we evaluated the performance of EasyM-a noninvasive, sensitive, MS-based assay for M-protein monitoring. EXPERIMENTAL DESIGN: Twenty-six patients enrolled in MCRN-001 clinical trial of two high-dose alkylating agents as conditioning followed by lenalidomide maintenance were selected for the study. All selected patients achieved complete responses (CR) during treatment, whereas five experienced progressive disease on study. The M-protein of each patient was first sequenced from the diagnostic serum using our de novo protein sequencing platform. The patient-specific M-protein peptides were then measured by targeted MS assay to monitor the response to treatment. RESULTS: The M-protein doubling over 6 months measured by EasyM could predict the relapse in 4 of 5 relapsed patients 2 to 11 months earlier than conventional testing. In 21 disease-free patients, the M-protein was still detectable by EasyM despite normal FLC and MRD negativity. Importantly, of 72 MRD negative samples with CR status, 62 were positive by EasyM. The best sensitivity achieved by EasyM, detecting 0.58 mg/L of M-protein, was 1,000- and 200-fold higher compared with serum protein electrophoresis and immunofixation electrophoresis, respectively. CONCLUSIONS: EasyM was demonstrated to be a noninvasive, sensitive assay with superior performance compared with other assays, making it ideal for multiple myeloma monitoring and relapse prediction.

Cervicogenic dizziness alleviation after coblation discoplasty: a retrospective study.

OBJECTIVE: Little is known about the therapeutic relationship between coblation discoplasty and cervicogenic dizziness (CGD). CGD can be caused by abnormal proprioceptive inputs from compressed nerve roots, intradiscal mechanoreceptors and nociceptors to the vestibulospinal nucleus in the degenerative cervical disc. The aim was to analyze the efficacy of coblation discoplasty in CGD through intradiscal nerve ablation and disc decompression in a 12-month follow-up retrospective study. METHODS: From 2015 to 2019, 42 CGD patients who received coblation discolplasty were recruited as the surgery group, and 22 CGD patients who rejected surgery were recruited as the conservative group. Using intent-to-treat (ITT) analysis, we retrospectively analyzed the CGD visual analogue scale (VAS), neck pain VAS, CGD frequency score, and the CGD alleviation rating throughout a 12-month follow-up period. RESULTS: Compared with conservative intervention, coblation discoplasty revealed a better recovery trend with effect sizes of 1.76, 2.15, 0.92, 0.78 and 0.81 in CGD VAS, and effect sizes of 1.32, 1.54, 0.93, 0.86 and 0.76in neck pain VAS at post-operative 1 week, and 1, 3, 6, 12 months, respectively. The lower CGD frequency score indicated fewer attacks of dizziness until postoperative 3 months (p < 0.01). At post-operative 12 months, the coblation procedure showed increased satisfactory outcomes of CGD alleviation rating (p < .001, -1.00 of effect size). CONCLUSIONS: Coblation discoplasty significantly improves the severity and frequency of CGD, which is important inbridging unresponsive conservative intervention and open surgery.Key messagesThere is a correlation between the degenerative cervical disc and cervicogenic dizziness (CGD).CGD can be caused by abnormal proprioceptive inputs from a compressed nerve root and intradiscal mechanoreceptors and nociceptors to the vestibulospinal nucleus in the degenerative cervical disc.Cervical coblation discoplasty can alleviate CGD through ablating intradiscal nerve endings and decompressing the nerve root.

Oxycodone versus other opioid analgesics after laparoscopic surgery: a meta-analysis.

BACKGROUND: Intravenous opioids are administered for the management of visceral pain after laparoscopic surgery. Whether oxycodone has advantages over other opioids in the treatment of visceral pain is not yet clear. METHODS: In this study, the analgesic efficiency and adverse events of oxycodone and other opioids, including alfentanil, sufentanil, fentanyl, and morphine, in treating post-laparoscopic surgery visceral pain were evaluated. This review was conducted according to the methodological standards described in the Cochrane Handbook for Systematic Reviews of Interventions and the Preferred Reporting Items for Systematic Reviews and Meta-analysis statement. The PubMed, Embase, and Cochrane databases were searched in December 2019. RESULTS: Ten studies were included in this review. The sample size was 695 participants. The results showed that compared with morphine and fentanyl, oxycodone had a more potent analgesic efficacy on the first day after laparoscopic surgery, especially during the first 0.5 h. There was no significant difference in sedation between the two groups. Compared to morphine and fentanyl, oxycodone was more likely to lead to dizziness and drowsiness. Overall, patient satisfaction did not differ significantly between oxycodone and other opioids. CONCLUSIONS: Oxycodone is superior to other analgesics within 24 h after laparoscopic surgery, but its adverse effects should be carefully considered.

Efficacy of coblation versus radiofrequency thermocoagulation for the clinical treatment of trigeminal neuralgia.

INTRODUCTION: Postoperative facial numbness is the main complication of radiofrequency thermocoagulation in treating trigeminal neuralgia, which could seriously affect the surgical efficacy. This problem is expected to be resolved by coblation technique. AIM: To compare the long-term efficacy and safety of coblation and percutaneous trigeminal radiofrequency thermocoagulation (PT-RFT) under fluoroscopic guidance in the treatment of trigeminal neuralgia (TN). MATERIAL AND METHODS: A case-control prospective study was carried out. Patients with TN were randomly scheduled to receive coblation or PT-RFT. Both surgical procedures were performed under fluoroscopic guidance. The data, including the degree of pain, pain relief and complications, were recorded during follow-up evaluation, which was performed on the first day and at the end of the first month, third month, sixth month and first year after surgery. RESULTS: A total of 50 patients were enrolled in this study, with 25 patients in each group. The visual analog scale (VAS) scores in both groups at each time point after surgery were significantly lower compared with before surgery (p < 0.05). There were no significant differences in VAS scores or pain relief between the two groups at any time point after surgery (p > 0.05). However, patients in the PT-RFT group exhibited greater facial numbness after surgery (p < 0.05). For other complications, there were no significant differences between the two groups (p > 0.05). CONCLUSIONS: Coblation and PT-RFT showed similar effectiveness in reducing pain; however, coblation was associated with a lower rate of postoperative facial numbness. Therefore, coblation may be a better treatment option for TN.

Computed Tomography-Guided Percutaneous Coblation of the Thoracic Nerve Root for Treatment of Postherpetic Neuralgia.

BACKGROUND: Postherpetic neuralgia (PHN) is one of the most intractable pain disorders and often does not respond to medication, physical, and interventional procedures. Coblation technology has been demonstrated to have potential for neuralgia, but there are rare reports of the efficacy and security of coblation for PHN. The thoracic segment is the most common predilection part of PHN, so we conducted this long-term study to investigate the results of coblation for the treatment of thoracic PHN. OBJECTIVES: The aim of this study was to determine the efficacy and security of computed tomography (CT)-guided coblation of the thoracic nerve root for treatment of PHN. STUDY DESIGN: Self before-after controlled clinical assessment. SETTING: Department of Pain Management, Xuanwu Hospital, Capital Medical University. METHODS: Seventy-seven patients with thoracic PHN sustained for at least 6 months and refractory to conservative therapy were identified. Patients underwent CT-guided percutaneous coblation to ablate the thoracic nerve root for thoracic PHN. The therapeutic effects were evaluated using a Visual Analog Scale (VAS), medication doses, and pain-related quality of life (QoL) scale before coblation, and at 1 week, and at 1, 3, and 6 months after the procedure. Patients who achieved more than 50% pain relief were defined as responders. In addition, adverse effects were also recorded to investigate the security of this procedure. RESULTS: The VAS score significantly decreased from 7.22 ± 1.15 before the coblation to 3.51 ± 1.12 (P = 0.01), 3.02 ± 1.21 (P = 0.006), 3.11 ± 2.15 (P = 0.014), and 2.98 ± 2.35 (P = 0.008) at 1 week, and at 1, 3, and 6 months after the procedure, respectively. The number of responders were 56 (77.78%), 54 (75%), 55 (76.39%), and 54 (75%) at 1 week, and at 1, 3, and 6 months after the procedure, respectively. The doses of anticonvulsants and analgesics were decreased significantly at all time points after the procedure compared with before treatment (P < 0.05). Patient responses on the Brief Pain Inventory Short Form indicated mean scores that were significantly lower than baseline across all domains of pain interference with QoL at all evaluations (P = 0.001). Most of the patients had mild numbness and it did not affect the daily activities after the procedure. No other severe adverse events occurred during or after the procedure. LIMITATIONS: A single-center study, relatively small number of patients, short duration of review of medical record, and the retrospective study. CONCLUSIONS: CT-guided percutaneous thoracic nerve root coblation is an effective and safe method for the treatment of thoracic PHN, and the procedure can also significantly improve the QoL in patients with PHN.

[The significance of evaluation of sleep respiration in infants with Pierre Robin sequence].

Objective:This study aimed to evaluate the sleep disorders of infants with Pierre Robin sequence by PSG, and to understand the sleep breathing characteristics of them. Method:Seventeen patients with Pierre Robin sequence underwent polysomnography lasting over 7 hours. Sleep apnea and oxygen index was recorded and analyzed. Result:14（82.35%） patients with Pierre Robin sequence presented with apnea, hypopnea and hypoxemia with varying degree. The apnea-hypopnea index（12.39±9.86） and lowest arterial oxygen saturation（84.12±8.12） %were not significantly different between sexes. However, age showed a negative impact with apnea-hypopnea index, which was worse in younger infants. Conclusion:Most patients with the Pierre Robin sequence have sleep apnea and hypoxemia, and appropriate management should be implemented in an early age. Polysomnography can provide objective analysis of the treatment.

Coblation annuloplasty in cervical discogenic pain without radiculopathy.

INTRODUCTION: The nerve fibers innervating the annulus fibrosus are the major origin of degeneration-associated discogenic pain. Coblation is a tissue-dissociating technique in which the nerve fibers in the degenerative disc tissue are ablated. We hypothesized that coblation annuloplasty would be an effective maneuver for cervical discogenic pain without radiculopathy. AIM: To observe the therapeutic efficacy of coblation annuloplasty in patients with cervical discogenic pain without radiculopathy. MATERIAL AND METHODS: Forty patients diagnosed with cervical discogenic pain without radiculopathy were screened for coblation annuloplasty therapy. The patient-rated visual analog scale (VAS) score for pain, significant pain relief rate, and Modified MacNab pain-relieving effect were adopted to evaluate the therapeutic effect within a 1-year follow-up period. RESULTS: Thirty-three patients eventually completed the study. The average pain duration was 4.6 ±1.6 years (range: 0.5-8 years). The mean VAS pain score decreased from preoperative 6.8 ±0.9 to postoperative 2.5 ±1.3 (p < 0.01). For all participants, the immediate pain relief rate was 78.7% (26/33), which continued to postoperative 6 months. One year later, 22 (66.6%) subjects reported that their pain was significantly alleviated. According to the Modified MacNab criteria, 63.6-82.1% considered the effect of surgery for their pain therapy as "excellent" during the 1-year follow-up period. No significant complications such as hemorrhage, paresthesia, or infection were observed. CONCLUSIONS: This study is the first to demonstrate that coblation annuloplasty is an effective intervention providing significant alleviation of neck pain from cervical discogenic injury without radiculopathy.

MTH1 inhibitor amplifies the lethality of reactive oxygen species to tumor in photodynamic therapy.

Although photodynamic therapy (PDT) has been clinically applied tumor hypoxia still greatly restricts the performance of this oxygen-dependent oncological treatment. The delivery of oxygen donors to tumor may produce excessive reactive oxygen species (ROS) and damage the peripheral tissues. Herein, we developed a strategy to solve the hypoxia issue by enhancing the lethality of ROS. Before PDT, the ROS-defensing system of the cancer cells was obstructed by an inhibitor to MTH1, which is a key for the remediation of ROS-caused DNA damage. As a result, both nuclei and mitochondrial DNA damages were increased, remarkably promoting cellular apoptosis. The therapeutic results demonstrated that the performance of PDT can be improved by the MTH1 inhibitor, leading to efficient cancer cell killing effect in the hypoxic tumor. This strategy makes better use of the limited oxygen, holding the promise to achieve satisfactory therapeutic effect by PDT without generating redundant cytotoxic ROS.

Double-crosslinked nanocomposite hydrogels for temporal control of drug dosing in combination therapy.

Temporal control of drug dosing is indispensable for a successful combination therapy that utilizes cisplatin (CDDP) and irinotecan (IRN), with clinical evidence supporting a higher response rate when CDDP was administered prior to IRN. Herein, a peptide-based nanocomposite hydrogel (CDDP/Pept-AlgNP/IRN) was designed for differential release of CDDP and IRN to maximize synergism of two drugs. First, a double-crosslinking strategy was exploited for structural reinforcement of hydrogel, with integration of coordination interactions between CDDP and hydrogelator (Pept) as well as electrostatic interactions between Pept and alginate nanoparticles (AlgNP/IRN), that afforded nanocomposite hydrogel with 42-fold increase in storage modulus comparing to peptide gel alone. Next, the nanocomposite hydrogel with excellent injectability served as a depot for controlled release of dual drugs, and guaranteed a fast release of CDDP prior to a tunable release of IRN that is dependent on fraction ratios of AlgNP in the composite materials. Comparing to simple mixture of CDDP and IRN solution, CDDP/Pept-AlgNP/IRN hydrogel formulation demonstrated excelling synergism of CDDP and IRN in cell inhibition studies, with efficacious antitumor potency further proved in tumor regression studies in vivo. We believe that the strategy of utilizing co-assembly of multiple pairs of entities (i.e. drug-gelator, nanoparticle-gelator) in composite materials provides a generalized method to design mechanically stable supramolecular hydrogels, and further promises an exact temporal control of drug dosing by packing individual drugs in co-assembled structures/domains to satisfy clinical demands from combination therapy. STATEMENT OF SIGNIFICANCE: This study reports the design of nanocomposite hydrogels with two distinct co-assembling domains for structural reinforcement of hydrogel and differential release of two drugs (CDDP and IRN) in combination therapy. We first investigated the effects of co-assembling processes for the reinforcement of hydrogel. Then we utilized the hydrogel for differential release of CDDP and IRN to achieve better synergistic efficacy of drugs in inhibiting the growth of cancer cell A549 and better anticancer efficacies than single drug formulations or solution mixtures of dual drugs in an A549-xenografted mouse model. We believe that the strategy of packing individual drugs in distinct co-assembling structures promises a paradigm shift for regulating temporal control of drug dosing in combination therapy.

A20-OVA Nanoparticles Inhibit Allergic Asthma in a Murine Model.

The skewed T helper (Th) 2 response plays a critical role in the pathogenesis of allergic asthma. Regulatory T (Treg) cells and the regulatory cytokines are required in maintaining the homeostasis in the body. This study aims to determine the effects of a poly(lactic-co-glycolic) acid (PLGA)-ovalbumin (OVA)+A20 (a ubiquitin E3 ligase) nanovaccine on inhibiting allergic asthma in a murine model. In this study, A20 and OVA (a model antigen) were encapsulated into PLGA to be a nanovaccine (PLGA-OVA+A20). An allergic asthma murine model was developed with OVA as the specific antigen to test the role of PLGA-OVA+A20 nanovaccine in maintaining the immune homeostasis in the airway tissues. The results showed that PLGA-OVA+A20 nanovaccine inhibited the asthma responses in mice by suppressing Th2 inflammatory responses, promoting the generation of Treg cells in the airway tissues. We conclude that the PLGA-OVA+A20 nanovaccine has a marked inhibitory effect on the airway allergic response in sensitized mice by significantly promoting the generation of Treg cell and IL-10. The data suggest that PLGA-OVA+A20 has translational potential in the treatment of allergic asthma.

Microvascular decompression and radiofrequency for the treatment of trigeminal neuralgia: a meta-analysis.

PURPOSE: Surgical treatments are used for trigeminal neuralgia (TN) when drug treatment fails. Surgical options can be divided into two categories: ablation (destructive) or non-ablation. Microvascular decompression (MVD) is primarily a non-ablation option, while radiofrequency thermocoagulation/rhizotomy (RF) is an ablation option. The aim of this study was to compare outcomes of MVD versus RF in the treatment of TN. MATERIALS AND METHODS: This article evaluates the clinical results and economic effectiveness of trigeminal nerve RF and MVD for the treatment of TN. This review was conducted according to the methodological standards described in the Cochrane Handbook for Systematic Reviews of Interventions and the Preferred Reporting Items for Systematic Reviews and Meta-analysis statement. The PubMed, Embase and Cochrane libraries were searched in January 2018. We have registered our review at the Review Registry. RESULTS: Nine studies were included in this review. The sample size was 2163 participants. The results showed that compared with RF, MVD had a lower risk of requiring a secondary procedure. The MVD group also had a lower risk of facial numbness. There was no significant difference in postoperative medication use between the two groups. Compared to RF, MVD was more likely to increase the risk of hypacusis and hypesthesia and to decrease the risk of facial pain and dysesthesia. The total cost of MVD, including the operation, hospital stay and additional procedures, was much higher than that of RF. CONCLUSION: MVD had a lower risk of requiring a secondary procedure and facial numbness after surgery. RF could be considered in patients who are unfit for MVD or refused invasive treatment.