Risk assessment and pathogen profile of surgical site infections in traumatic brain injury patients undergoing emergency craniotomy: A retrospective study.

Emergency craniotomy in patients with traumatic brain injury poses a significant risk for surgical site infections (SSIs). Understanding the risk factors and pathogenic characteristics of SSIs in this context is crucial for improving outcomes. This comprehensive retrospective analysis spanned from February 2020 to February 2023 at our institution. We included 25 patients with SSIs post-emergency craniotomy and a control group of 50 patients without SSIs. Data on various potential risk factors were collected, including demographic information, preoperative conditions, and intraoperative details. The BACT/ALERT3D Automated Bacterial Culture and Detection System was utilized for rapid bacterial pathogen identification. Statistical analyses included univariate and multivariate logistic regression to identify significant risk factors for SSIs. The study identified Klebsiella pneumoniae, Escherichia coli, and Staphylococcus aureus as the most prevalent pathogens in SSIs. Significant risk factors for SSIs included the lack of preoperative antibiotic use, postoperative drainage tube placement, diabetes mellitus, and the incorporation of invasive procedures, all of which showed a significant association with SSIs in the univariate analysis. The multivariate analysis further highlighted the protective effect of preoperative antibiotics and the increased risks associated with anaemia, diabetes mellitus, postoperative drainage tube placement, and the incorporation of invasive procedures. Our research underscores the critical role of factors like insufficient preoperative antibiotics, postoperative drainage, invasive techniques, anaemia, and diabetes mellitus in elevating the risk of surgical site infections in traumatic brain injury patients undergoing emergency craniotomy. Enhanced focus on these areas is essential for improving surgical outcomes.

Safety, pharmacokinetics, and efficacy of rifasutenizol, a novel dual-targeted antibacterial agent in healthy participants and patients in China with Helicobacter pylori infection: four randomised clinical trials.

BACKGROUND: Due to the rapid development of antimicrobial resistance, the efficacy of most Helicobacter pylori eradication therapies have progressively decreased to an unacceptable level. Rifasutenizol (TNP-2198) is a new molecular entity with a synergistic dual mechanism of action currently under clinical development for the treatment of microaerophilic and anaerobic bacterial infections. We aimed to evaluate the safety, pharmacokinetics, and efficacy of rifasutenizol in healthy Chinese participants and patients with H pylori. METHODS: We conducted four clinical trials of rifasutenizol capsules in healthy participants (aged 18-55 years) and patients with asymptomatic H pylori infection (aged 18-65 years) in a clinical trial centre in Jilin province, China. Trial 1 was a phase 1, double-blind, randomised, placebo-controlled, single ascending dose study, in which participants were enrolled into one of seven rifasutenizol dose groups (50 mg, 100 mg, 200 mg, 400 mg, 600 mg, 800 mg, or 1000 mg) and were randomly assigned in a 4:1 ratio to study drug or placebo. Trial 2 was a phase 1, double-blind, randomised, placebo-controlled, multiple ascending dose study, in which patients were enrolled into one of three rifasutenizol dose groups (200 mg, 400 mg, or 600 mg) and were randomly assigned in a 3:1 ratio to study drug or placebo. Trial 3 was a phase 2a, open-label, randomised, multiple-dose, dose-finding study in which patients enrolled into one of four cohorts were randomly assigned in a 1:1:1:1 ratio to a rifasutenizol dual or triple regimen. Trial 4 was a phase 2b, open-label, randomised, multiple-dose, regimen exploration study, in which patients enrolled into one of five cohorts were randomly assigned in a 2:2:1:1:2 ratio to a rifasutenizol dual therapy, triple therapy, or a control cohort. Block randomisation (block size 4 or 8) was used in all four trials. The key primary endpoints for trials 1, 2, and 3 were the tolerability, safety, and pharmacokinetics of rifasutenizol. For trial 4, the primary endpoint was the eradication rate of H pylori. These four trials were registered at ClinicalTrials.gov (NCT06081699, NCT06081712, NCT06076681, and NCT06076694) and chinadrugtrials.org.cn (CTR20190734, CTR20192553, CTR20212050, and CTR20220625) and are completed. FINDINGS: Between May 9, 2019, and Sept 14, 2022, 78 healthy participants (trial 1: n=10 per cohort in a 4:1 rifasutenizol:placebo ratio; and an additional eight for the food-effect cohort) and 168 patients with asymptomatic H pylori infection (trial 2: n=16 per cohort in a 3:1 rifasutenizol:placebo ratio; trial 3: n=10 per cohort; trial 4: n=10 or n=20 per cohort) were enrolled in the four clinical trials. Single doses of rifasutenizol (50-1000 mg) and multiple doses of rifasutenizol (200 mg to 600 mg, twice a day), either as monotherapy or co-administered with rabeprazole and amoxicillin, showed favourable safety and tolerability profiles. Most adverse events were mild, and no serious adverse events were reported. Rifasutenizol demonstrated a linear pharmacokinetic profile over the dose range of 50-800 mg, and there were no apparent pharmacokinetic interactions between rifasutenizol and the co-administrated drugs. Food intake slightly elevated the area under the plasma concentration-time curve (AUC) of rifasutenizol, and the geometric mean of AUC from time 0 to the last timepoint with a quantifiable concentration (AUC0-t) and AUC from time 0 to infinity (AUC0-∞) in the fed state were 1·334 and 1·396 times of those in the fasted state, respectively. There was mild accumulation after continuous administration of rifasutenizol, and the Rac(AUC) of rifasutenizol 400 mg in the dual and triple regiments in trial 3 were 1·37 and 1·49, respectively. In trial 3, the eradication rates of H pylori with 200 mg, 400 mg, or 600 mg of rifasutenizol in combination with rabeprazole, twice a day for 14 days, were 0% (95% CI 0-31), 30% (7-65), and 40% (12-74), respectively, identifying rifasutenizol 400 mg as the effective dose. In trial 4, H pylori eradication rates with the triple regimen in cohort A (400 mg rifasutenizol, 20 mg rabeprazole sodium, and 1 g amoxicillin) twice a day for 14 days was 95% (95% CI 74-100), and triple therapy (600 mg rifasutenizol, 20 mg rabeprazole sodium, and 1 g amoxicillin) three times a day for 7 days was 100% (69-100). INTERPRETATION: Rifasutenizol monotherapy and combination therapy was generally safe and well tolerated in healthy participants and patients with H pylori infection. A triple regimen of 400 mg rifasutenizol capsules, 20 mg rabeprazole sodium enteric-coated tablets, and 1 g amoxicillin capsules twice a day for 14 days showed promising efficacy as a new treatment regimen for H pylori infection. FUNDING: TenNor Therapeutics and National Natural Science Foundation of China. TRANSLATION: For the Chinese translation of the abstract see Supplementary Materials section.

Safety, Tolerability, Pharmacokinetics, and Immunogenicity of the Anti-IFNAR1 Monoclonal Antibody QX006N: A First-in-Human Single Ascending Dose Study in Healthy Chinese Volunteers.

BACKGROUND AND OBJECTIVE: QX006N is a novel, humanized, IgG4κ monoclonal antibody targeting IFNAR1, developed for the treatment of systemic lupus erythematosus. This study aims to investigate the pharmacokinetics, safety, tolerability, and immunogenicity of QX006N when administered intravenously to healthy Chinese individuals. METHODS: A double-blind, randomized, placebo-controlled, single-ascending-dose, phase I clinical trial was conducted comprising five cohorts (n = 10 per cohort, except n = 5 for the first cohort). Subjects in each cohort were randomly assigned in a 4:1 ratio to receive a single intravenous infusion of QX006N (0.3 mg/kg, 1.0 mg/kg, 3.0 mg/kg, 6.0 mg/kg, or 10.0 mg/kg) or placebo for 30 minutes. Tolerability assessments included adverse events, vital signs, 12-lead electrocardiogram, physical examination, and clinical laboratory tests. The serum concentration of QX006N was measured using the enzyme-linked immunosorbent assay method, and the anti-drug antibodies were detected using the electrochemiluminescence assay method. RESULTS: QX006N demonstrated a favorable safety and tolerability profile throughout the study. All treatment-emergent adverse events were of Grade 1-2 (CTCAE Version 5.0), and no serious adverse events, deaths, or drug discontinuations because of treatment-emergent adverse events were observed. All drug-related treatment-emergent adverse events showed no clear dose-related trends. Following an intravenous infusion of QX006N at doses that ranged from 0.3 mg/kg to 10 mg/kg, the half-life increased from 24.7 to 208 hours in a dose-dependent manner, while clearance decreased from 0.0828 to 0.0065 L/h. The maximum concentration exhibited nearly dose-proportional increases, and the area under the curve displayed a more than dose-proportional increment with non-linear pharmacokinetic characteristics. The incidence of anti-drug antibodies was observed to increase over time for doses that ranged from 1.0 mg/kg to 10.0 mg/kg of QX006N, reaching its peak at day 57 (range 62.50-87.50%). Conversely, the incidence of anti-drug antibodies in the QX006N 0.3-mg/kg and placebo cohorts remained low. CONCLUSIONS: QX006N demonstrated acceptable safety, tolerability, and pharmacokinetic characteristics in healthy subjects when administered as a single intravenous infusion at doses that ranged from 0.3 mg/kg to 10.0 mg/kg. Based on the pharmacokinetic and safety outcomes, a recommended effective dose of 300 mg is proposed for future phase Ib studies. CLINICAL TRIAL REGISTRATION: This study has been registered at http://www.chinadrugtrials.org.cn/ under identifier CTR20212834.

ZSP1601, a novel pan-phosphodiesterase inhibitor for the treatment of NAFLD, A randomized, placebo-controlled phase Ib/IIa trial.

Non-alcoholic fatty liver disease is a growing health burden with limited treatment options worldwide. Herein we report a randomized, double-blind, placebo-controlled, multiple-dose trial of a first-in-class pan-phosphodiesterase inhibitor ZSP1601 in 36 NAFLD patients (NCT04140123). There were three cohorts. Each cohort included twelve patients, nine of whom received ZSP1601 50 mg once daily, 50 mg twice daily, or 100 mg twice daily, and three of whom received matching placebos for 28 days. The primary outcomes were the safety and tolerability of ZSP1601. A total of 27 (27/36, 75%) patients experienced at least one treatment-emergent adverse event (TEAE). Most TEAEs were mild to moderate. There was no Serious Adverse Event. Diarrhea, transiently elevated creatinine and adaptive headache were frequently reported adverse drug reaction. We conclude that ZSP1601 is well-tolerated and safe, showing effective improvement in liver chemistries, liver fat content and fibrosis in patients with NAFLD.

Analysis of the influence factors of cervical lymph node metastasis in Papillary thyroid carcinoma: A retrospective observational study.

Papillary thyroid carcinoma (PTC) is the most common type of thyroid cancer, and surgery is crucial for curing PTC. PTC patients often experience lymph node metastasis (LNM) in the neck, and central lymph node metastasis (CLNM) significantly affects the recurrence rate of PTC. Therefore, the thoroughness of the surgery is particularly important for the treatment of PTC. However, there is still controversy regarding the choice of surgical approach. This study retrospectively analyzed the clinical data of 69 PTC patients treated at our hospital from December 2019 to April 2022 and clinically analyzed the high-risk factors for neck LNM. In this study, the patients aged ≤ 55 years were examined in which the number of patients with CLNM were 42 cases (80.77%), tumor diameter >2 cm were 15 cases (100%), the multifocal carcinoma were 38 cases (88.37%) and the involvement of membrane were 38 cases (80.85%), the number of patients whose had lateral cervical lymph node metastasis (LLNM), respectively 43 cases (82.69%), 14 cases (93.33%), 39 cases (90.7%) and 40 cases (85.11%),all of these factors were associated with cervical LNM (P < .05), but was not correlation with sex, double lobe carcinoma, extra glandular invasion and hashimoto (P > .05). The patient's age and number of cancers were independent risk factors for LNM in the central region of the neck (P < .05), while the patient's age, tumor size and number of cancers were significant risk factors for LNM in the lateral cervical region (P < .05). We concluded that cervical LNM was related with the high-risk factors of patient's age, tumor size, multifocal carcinoma in PTC. Especially, modified radical cervical dissection or selective cervical dissection was suggested in the PTC patients who were younger than 42.5 years old, with tumor diameter larger than 2 cm and multifocal carcinoma.

Endoscopic total parathyroidectomy via anterior chest approach with forearm autotransplantation for secondary hyperparathyroidism: a comparison of surgical results with open total parathyroidectomy with autotransplantation.

Objective: This paper aimed to evaluate the clinical value of performing an endoscopic total parathyroidectomy through anterior chest approach with autotransplantation (EACtPTx+AT) in treating secondary hyperparathyroidism (SHPT) to summarize and share the clinical experience. Methods: 24 patients with SHPT were retrospectively analyzed:11 patients underwent open total parathyroidectomy with autotransplantation (OtPTx+AT Group) and 13 patients underwent endoscopic parathyroidectomy through anterior chest approach with autotransplantation (EACtPTx+AT Group). Comparing the two groups regarding the following factors: (1) operating conditions, such as the blood loss during the operation, the length of time spent on the operating table, the number of parathyroid glands removed, postoperative drainage volume and hospital stay. (2) clinical efficacy, parathyroid hormone (PTH) and serum calcium (Ca) levels. (3) postoperative complications. Results: First, there were no significant differences in the number of parathyroid gland resection, operation time, intraoperative blood loss and hospital stay between the two groups. While there were significant differences in postoperative drainage volume between the two groups. Second, the two groups preoperative PTH and preoperative serum calcium decreased significantly compared with those of the two groups after surgery and there was a statistically significant difference. Thirdly, there was no postoperative bleeding, hoarseness or choking in the two groups and no conversion to open surgery case in EACtPTx+AT group. Conclusion: Endoscopic treatment of SHPT using the anterior chest approach with forearm autotransplantation significantly improves clinical symptoms and lowers levels of PTH and serum calcium after the operation. The results confirm the operation's safety and effectiveness.

Safety, pharmacokinetics and pharmacodynamics of a novel γ-aminobutyric acid (GABA) receptor potentiator, HSK3486, in Chinese patients with hepatic impairment.

BACKGROUND: The primary objective of this study was to investigate if hepatic impairment alters the safety, pharmacokinetics, and pharmacodynamics of HSK3486. RESEARCH DESIGN AND METHODS: This was a clinical trial of HSK3486 in subjects with normal hepatic function (n = 8), and mild (Child-Pugh A; n = 8), or moderate (Child-Pugh B; n = 8) hepatic impairment. Each subject received an IV bolus dose of 0.4 mg/kg HSK3486 for 1 min, immediately followed by a maintenance infusion of 0.4 mg/kg/h HSK3486 for 30 min. RESULTS: In total, 24 subjects were enrolled and completed the study. HSK3486 was generally well tolerated by all subjects. There were no serious AEs and no deaths reported during the study. The incidence of AEs was numerically highest in subjects with moderate hepatic impairment. The exposure (AUC) of HSK3486 increased gradually with the decrease in hepatic function; however, degree of hepatic impairment had little effect on HSK3486 PD (MOAA/S and BIS). CONCLUSIONS: Overall, there were no clinically relevant differences in HSK3486 exposure or PD in subjects with mild or moderate hepatic impairment compared to normal control. These data imply that HSK3486 dose adjustment is not warranted in subjects with mild or moderate hepatic impairment. TRIAL REGISTRATION: The trial is registered at ClinicalTrials.gov (CT.gov identifier: NCT04145596).Key MessageHSK3486 at an IV bolus dose of 0.4 mg/kg and a maintenance infusion of 0.4 mg/kg/h was safe and well tolerated by all mild or moderate hepatic impairment subjects and normal hepatic function subjects.There were no clinically relevant differences in HSK3486 exposure or PD in subjects with mild or moderate hepatic impairment compared to subjects with normal hepatic function.HSK3486 dose adjustment is not required in subjects with mild or moderate hepatic impairment.

First-In-Human Study on Pharmacokinetics, Safety, and Tolerability of Single and Multiple Escalating Doses of Hepenofovir, a Novel Hepatic Targeting Prodrug of Tenofovir in Healthy Chinese Subjects.

Objective: Hepenofovir, a novel hepatic targeting prodrug of tenofovir, has been developed for the treatment of chronic hepatitis B (CHB). This is a first-in-human study to evaluate the pharmacokinetics (PK) and tolerability of single and multiple escalating doses of hepenofovir in healthy Chinese subjects. Methods: This phase Ia study included two parts: a double-blinded, randomized, placebo-controlled single-ascending-dose (SAD) (25-200 mg) study under fasted conditions comprising a food-effect investigation (200 mg) and a multiple-ascending-dose (MAD) (25 mg) study under fasted conditions. Results: Hepenofovir was well tolerated in healthy Chinese subjects. There was no significant difference in adverse reaction rates between hepenofovir and placebo groups. Hepenofovir was rapidly absorbed and metabolized into tenofovir after dosing. In healthy participants, the median Tmax of hepenofovir and tenofovir was 0.33-0.50 h and 0.62-0.75 h, respectively, and their mean half-life was 2.5-12.3 h and 49.7-53.8 h, respectively. Systemic exposure to tenofovir increased in proportion to the dose. The mean accumulation indexes of hepenofovir and tenofovir were 1.1 vs. 1.8. Moreover, food could reduce the Cmax of both hepenofovir and tenofovir, but did not affect their area under the curve (AUC). Conclusions: Hepenofovir has shown a favorable safety and PK profile, which support the further evaluation of its safety and efficacy in CHB patients. Clinical trial registration number: The trial is registered at Chinese Clinical Trial website (http://www.chinadrugtrials.org.cn/index.html # CTR20191953).

Pharmacokinetics, safety, and tolerability of TQC3564, a novel CRTh2 receptor antagonist: report of the first-in-human single- and multiple-dose escalation trials in healthy Chinese subjects.

BACKGROUND: This is the first-in-human study to evaluate the pharmacokinetics, safety, and tolerability of TQC3564 (a novel CRTh2 receptor antagonist) in healthy Chinese subjects. RESEARCH DESIGN AND METHODS: This project was a phase Ia clinical study of TQC3564 as a single-ascending dose (SAD) (25 to 1200 mg) and a multiple-ascending dose (MAD) (100 or 500 mg, QD) as well as a two-period crossover food-effect study (300 mg). RESULTS:     In the SAD and MAD study, TQC3564 were found to be safe and well tolerated, without dose-dependent adverse events (AEs), and all AEs were mild or moderate in severity. In the SAD study, the median tmax of TQC3564 was 2.5-4.5 h, and t1/2 was 8.13-35.7 h. Exposure was increased after food intake. The MAD study results showed that steady-state was achieved on day 4. Moreover, no apparent TQC3564 plasma accumulation was detected on day 7. CONCLUSIONS: In healthy subjects, TQC3564 at a single dose of 25-1200 mg or 100-500 mg at multiple doses (QD) was safe and tolerable with acceptable PK profiles, indicating that TQC3564 has potential as a therapeutic option for asthma. (This study has been registered at http://www.chinadrugtrials.org.cn/ under identifier CTR20192397.).

Safety, Tolerability, and Pharmacokinetics of the Novel Hepatitis B Virus Expression Inhibitor GST-HG131 in Healthy Chinese Subjects: a First-in-Human Single- and Multiple-Dose Escalation Trial.

GST-HG131, a novel dihydroquinolizinone (DHQ) compound, has been shown to reduce circulating levels of HBsAg in animals. This first-in-human trial evaluated the safety, tolerability, and pharmacokinetic profile of GST-HG131 in healthy Chinese subjects. This was a double-blind, randomized, placebo-controlled phase Ia clinical trial that was conducted in two parts. Part A was a single-ascending-dose (SAD; GST-HG131 10 30, 60, 100, 150, 200, 250 or 300 mg or placebo) study, which also assessed the food effect of GST-HG131 100 mg. Part B was a multiple-ascending-dose (MAD; GST-HG131 30, 60 or 100 mg or placebo BID) study. Tolerability assessments included adverse events, vital signs, 12-lead electrocardiogram, physical examination, and clinical laboratory tests. PK analyses were conducted in blood, urine, and fecal samples. Single doses of GST-HG131 ≤ 300 mg and multiple doses of GST-HG131 ≤ 60 mg were generally safe and well tolerated; however, multiple dosing was stopped at GST-HG131 100 mg, as pre-defined stopping rules specified in the protocol were met (Grade II drug related AEs of nausea and dizziness in >50% of subjects). In the SAD study, median tmax of GST-HG131 was 1-6 h, and t1/2 ranged from 3.88 h to 14.3 h. PK parameters were proportional to dose. Exposure was reduced after food intake. In the MAD study, steady-state was attained on day 4, and there was no apparent plasma accumulation of GST-HG131 on day 7 (Racc < 1.5). In conclusion, GST-HG131 exhibited an acceptable safety profile in healthy subjects at single doses ranging from 10-300 mg and multiple doses (BID) ranging from 30-60 mg, and the MAD doses (30 mg and 60 mg BID) that potentially meet the therapeutic AUC requirements. These findings imply GST-HG131 has potential as a therapeutic option for CHB infection. (This study has been registered at ClinicalTrials.gov under identifier NCT04499443.).

Estimating construction waste generation in the Greater Bay Area, China using machine learning.

Reliable construction waste generation data is a prerequisite for any evidence-based waste management effort, but such data remains scarce in many developing economies owing to their rudimentary recording systems. By referring to several models proposed for estimating waste generation, this study aims to develop a reliable and accessible method for estimating construction waste generation based on limited publicly available data. The study has two objectives. Firstly, it aims to estimate construction waste generation by focusing on the Greater Bay Area (GBA) in China, one of the world's most thriving regions in terms of construction activities. Secondly, it aims to compare the strengths and weaknesses of various waste quantification models. 43 sets of annual socio-economic, construction-related and C&D waste generation data ranging from 2005 to 2019 were collected from the local government authorities. By analyzing the data using four types of machine learning models, namely multiple linear regression, decision tree, grey models, and artificial neural network, it is found that all calibrated models, with their respective strengths and weaknesses, can produce acceptable results with the testing R2 ranging from 0.756 to 0.977. This study also reveals that the 11 cities in the GBA produced a total of about 364 million m3 of construction waste in 2018. The result can be used for monitoring the urban metabolism, quantifying carbon emission, developing a circular economy, valorizing recycled materials, and strategic planning of waste management facilities in the GBA. The research findings also contribute to the methodologies for estimating waste generation using limited data.

Knocking down LINC01116 can inhibit the regulation of TGF-ß through miR-774-5p axis and inhibit the occurrence and development of glioma.

BACKGROUND: Many studies have shown that non-coding RNAs (ncRNAs), including long non-coding RNA (LncRNA) and micro RNA (miRNA), play a crucial regulatory role in glioma. LINC01116 is a newly discovered LncRNA, and the relationship between LncRNA and glioma is still under exploration. METHOD: LncRNAs with potential differences were screened through GEO database, and the expressions of LINC01116 and miR-744-5p/TGF-ß1 in glioma tissues were tested using qRT-PCR. Changes in proliferation and migration/invasion of glioma were tested using CCK-8 and transwell assay. The expression changes of TGF-ß1 were tested using qRT-PCR and Western blot. Targeted binding among LINC01116, miR-744-5p and TGF-ß1 was verified using double luciferase reporter, RNA Immunoprecipitation (PIR) and RNA pull-down experiments. The effect of LINC01116 on tumor growth was determined by tumor allografting test. RESULTS: GEO database and clinical research revealed that the expression level of LINC01116 in glioma increased, and the elevation of LINC01116 was closely related to the adverse prognosis of clinical patients. Functional experiments showed that the inhibition of LINC01116 could up-regulate miR-744-5p-mediated proliferation and metastasis of glioma cells. Western blot analysis and qRT-PCR analysis showed that LINC01116 regulated TGF-ß1 by mediating miR-744-5p. Further cell behavior experiments showed that LINC01116 acted as miR-744-5p sponge to inhibit proliferation and metastasis caused by TGF-ß1. Finally, the analysis of animal models in vivo showed that LINC01116 could regulate the tumor growth of glioma. CONCLUSION: LncRNA LINC01116 acts as an oncogene and promotes TGF-ß1 mediated proliferation and metastasis by acting as competitive endogenous RNA (ceRNA) in glioma.

lncRNA TTN­AS1 upregulates RUNX1 to enhance glioma progression via sponging miR­27b­3p.

Long non­coding RNAs (lncRNAs) contribute to the tumorigeneses of numerous types of cancer, including glioma. The present study was designed to unveil a novel lncRNA functioning in glioma and explore the underlying mechanisms. lncRNA titin­antisense RNA1 (TTN­AS1), miR­27b­3p and Runt­related transcription factor 1 (RUNX1) expression in glioma tissues and cell lines was estimated by RT­qPCR. Si­TTN­AS1 was transfected into glioma cell lines (U251 and LN229), and CCK­8 assay, flow cytometry, wound healing and Transwell assays were applied to estimate the function of TTN­AS1 in glioma cells. miR­27b­3p inhibitor was used to explore the mechanisms. The results revealed that TTN­AS1 was highly expressed in glioma specimens and cell lines. Downregulation of TTN­AS1 inhibited the proliferation, migration and invasion of the glioma cells, as well as increased the rate of apoptosis. In vivo, the tumor growth was also inhibited by TTN­AS1 depletion in nude mice. Furthermore, we revealed that TTN­AS1 exerted oncogenic effects via sponging miR­27b­3p and thereby positively regulating RUNX1 expression. In conclusion, the present study supported that TTN­AS1 acts as an oncogene in glioma by targeting miR­27b­3p to release RUNX1. This finding may contribute to gene therapy of glioma.

Analgesic effect of the ultrasound-guided subcostal approach to transmuscular quadratus lumborum block in patients undergoing laparoscopic nephrectomy: a randomized controlled trial.

BACKGROUND: Quadratus lumborum block (QLB) is an effective analgesia that lowers opioid consumption after lower abdominal and hip surgeries. The subcostal approach to transmuscular QLB is a novel technique that can provide postoperative analgesia by blocking more dermatomes. The aim of this study is to evaluate the efficacy and viability of subcostal approach to QLB after laparoscopic nephrectomy. METHODS: Sixty patients who underwent laparoscopic nephrectomy were randomly divided into the subcostal approach to QLB group (QLB group, n = 30) and the control group (C group, n = 30). All patients underwent ultrasound-guided subcostal approach to QLB in an ipsilateral parasagittal oblique plane at the L1-L2 level. The QLB group received 0.4 cc/kg of 0.3% ropivacaine, and the C group received 0.4 cc/kg of 0.9% saline. Postoperatively, a patient-controlled intravenous analgesic pump with sufentanil was attached to all the patients. The primary outcome was sufentanil consumption within the first 24 h after surgery. The secondary outcomes included the Ramsey sedation scale (RSS) scores and Bruggemann comfort scale (BCS) scores 6 h (T1), 12 h (T2), and 24 h (T3) after surgery, intraoperative remifentanil consumption, number of patients requiring rescue analgesia, time to recovery of intestinal function, mobilization time after surgery, and presence of side effects. RESULTS: Sufentanil consumption within the first 24 h after surgery was significantly lower in the QLB group than in the C group (mean [standard deviation]: 34.1 [9.9] µg vs 42.1 [11.6] µg, P = .006). The RSS scores did not differ between the two groups, and the BCS scores of the QLB group at T1 and T2 time points was significantly higher than those of the C group(P<0.05). The consumption of remifentanil intraoperatively and the number of patients requiring rescue analgesia were significantly lower in the QLB group (P<0.05). Time to recovery of intestinal function and mobilization time after surgery were significantly earlier in the QLB group (P<0.05). The incidence of postoperative nausea and vomiting was significantly lower in the QLB group (P<0.05). CONCLUSIONS: The ultrasound-guided subcostal approach to QLB is an effective analgesic technique in patients undergoing laparoscopic nephrectomy as it reduces the consumption of sufentanil postoperatively. TRIAL REGISTRATION: ChiCTR1800020296 0 (Prospective registered). Initial registration date was 22/12/2018.

Effects of MiR-107 on The Chemo-drug Sensitivity of Breast Cancer Cells.

BACKGROUND: A growing body of evidence indicates that aberrant expression of miR-107 plays a core role in cancers. This study aims to demonstrate the function of miR-107 and its roles in chemo-drug resistance in breast cancer cells. METHODOLOGY: CCK-8 assays were carried out to test the effect of miR-107 mimics on the proliferation of MCF-7 cells. The apoptosis level of each group was detected by flow cytometry. miR-107 level, mRNA levels of Bcl-2/Bax and TRIAP1 were detected by quantitative real-time Polymerase Chain Reaction (qRT-PCR) analysis. Protein levels of Bcl-2/Bax, p-Akt/Akt in MCF-7 cells were detected by using Western Blot. Lastly, the dual luciferase reporter gene assay system was used to confirm interaction between miR-107 and its target gene TRIAP1. RESULTS: CCK-8 assays indicated that miR-107 mimics augmented Taxol-induced cell viability inhibition. Flow cytometry showed that miR-107 mimics augmented Taxol-induced elevation of cell apoptosis. qRT-PCR analysis revealed that miR-107 mimics inhibited the mRNA expression of Bcl-2 and induced the mRNA level of Bax. Western Blotting indicated that miR-107 mimics inhibited the expression of proteins Bcl-2 and p-Akt, and induced the expression of Bax, while showing no significant effects on Akt. The relative luciferase activity revealed that oncogene TRIAP1 is a potential target gene of miR-107. CONCLUSIONS: miR-107 plays a role in regulating chemo-drug sensitivity in mammary cancer cell by targeting TRIAP1.

Clinical evaluation of efficacy, tolerability and pharmacokinetics of yimitasvir phosphate in patients infected with hepatitis C virus.

OBJECTIVE: Yimitasvir phosphate, an inhibitor of nonstructural protein 5A (NS5A) replication complex of hepatitis C virus (HCV), was evaluated in a double-blind, placebo-controlled, parallel, multiple-dose study. METHODS: Twenty-four patients with chronic HCV genotype 1 infection were randomized to receive a 7-day course of yimitasvir phosphate at daily doses of 30, 100 or 200 mg or placebo. Antiviral efficacy, resistance profile, pharmacokinetics (PK), safety and tolerability were assessed. KEY FINDINGS: The maximal reduction in HCV RNA from baseline was 5.17 log10 IU/ml. However, most patients experienced viral rebound on or before day 3 after yimitasvir treatment was initiated. The PK profile revealed median peak plasma concentrations at 4-12 h postdose and a mean terminal half-life of 14.47-17.09 h, the basis for daily dosing. Steady drug state was achieved following 5 days of daily dosing. The accumulation rate was low (1.29-1.73). There were no significant alterations in vital signs and laboratory findings among all participants. CONCLUSIONS: This study shows that yimitasvir phosphate was well tolerated, and the PK profile supported daily dosing regimens. A 1-week (7-day) treatment course led to a quick and significant reduction in HCV RNA level in this cohort with HCV GT-1 infection.

Tolerability, pharmacokinetics and antiviral activity of rHSA/IFNα2a for the treatment of chronic hepatitis B infection.

AIMS: A recombinant human serum albumin-interferon alpha2a fusion protein (rHSA/IFNα2a) is expected to extend the half-life of IFNα2a. This study aims to evaluate the tolerability, safety and efficacy of rHSA/IFNα2a. METHODS: This is an open, randomized, positive control, multiple-dose ascending Phase Ib study. A panel of 32 treatment naïve and non-cirrhotic chronic hepatitis B patients were divided into four cohorts, and each received 600, 750 or 900 µg of rHSA/IFNα2a or 180 µg of PEG-IFNα2a for 3 months. Tolerability, pharmacokinetics and antiviral responses were assessed. RESULTS: Thirty-one of 32 enrolled patients completed the treatment study. The rHSA/IFNα2a treatment was better tolerated than the PEG-IFNα2a 180 µg treatment, as evidenced by blood cell counts and higher serum albumin levels. Half-life (t1/2 ) of rHSA/IFNα2a was estimated to be 120-140 h, and is potentially suitable for a dosing interval of 2 weeks or longer. Pharmacokinetics of the last dose between rHSA/IFNα2a 750 µg and PEG-IFNα2a 180 µg, with the exception of t1/2 , was comparable, and a similar kinetics of inhibiting HBV DNA replication was observed in both groups. Mean reductions in serum HBV DNA levels after treatment were -1.32, -2.13, -1.10 and -2.48 log10 IU/ml in the 600, 750 and 900 µg rHSA/IFNα2a groups and PEG-IFNα2a group, respectively. CONCLUSIONS: The rHSA/IFNα2a treatment was well tolerated and can be administered biweekly. Similar efficacy in inhibiting HBV replication was observed in both PEG-IFNα2a and rHSA/IFNα2a 750 µg groups.