珍珠（层）在骨组织修复中的研究进展

目的: 对珍珠(层)的成骨性及其在骨组织工程中的应用研究进展进行综述。方法: 广泛查阅近年来国内外相关文献,并进行总结。结果: 珍珠(层)粉是具有一定成骨作用的天然有机-无机复合材料,可以作为骨组织工程支架材料,而纳米级珍珠(层)粉具有更好的生物降解性和成骨作用。结论: 珍珠(层)在骨组织工程中具有潜在的应用前景,但制备出各种符合临床实际应用的骨修复材料仍需进一步研究。     

36例鼻眶沟通性黏液囊肿的手术治疗分析

目的 探讨应用鼻内镜手术治疗鼻眶沟通性黏液囊肿的效果和联合外路手术的适应证。方法 回顾性分 析接受手术治疗的鼻眶沟通性黏液囊肿患者的病历资料,分析手术入路和治疗效果。结果 纳入36例患者的54个 副鼻窦黏液囊肿,包括额窦29个、筛窦21个、蝶窦2个、上颌窦2个。囊肿侵犯眼眶外上/外下象限6例,内上/内下象 限30例。22例（61.1%）采用鼻内镜手术,均为囊肿侵犯眼眶内上/内下象限。14例（38.9%）采用鼻内镜-外路联合手 术,其中8例侵犯眼眶内上/内下象限,6例侵犯眼眶外上/外下象限。2种手术术后眼球突出等症状均明显缓解。外 路手术出现脑脊液漏1例,鼻内镜手术出现中鼻甲粘连1例。随访12~61个月,手术后窦口再狭窄的发生率为8.3% （3/36）,均发生在额窦手术后。鼻内镜手术未见囊肿复发,鼻内镜-外路联合手术1例复发。结论 鼻内镜手术治疗 鼻眶沟通性黏液囊肿安全、可行,对于囊肿在额窦外侧远端、侵犯眼眶外上/外下象限、额筛窦囊肿伴厚壁骨性间隔 者,可选择鼻内镜-外路联合手术治疗。     

Ultrasound-Guided Transmuscular Quadratus Lumbar Block Reduces Opioid Consumption after Laparoscopic Partial Nephrectomy

Objectives Transmuscular quadratus lumborum block (TQLB) may provide postoperative analgesia in patients undergoing intraperitoneal surgeries. The purpose of this study was to examine the potential efficacy of TQLB among patients undergoing retroperitoneal procedures, such as the laparoscopic partial nephrectomy (LPN).Methods This prospective, randomized, controlled study was conducted from August 2017 to November 2018 at Peking Union Medical College Hospital (Beijing, China). Patients who were scheduled for a LPN, aged 18-70 years old with an ASA physical status score of I - II were randomly assigned to receive either TQLB with 0.6 ml/kg of 0.5% ropivacaine plus general anesthesia (TQLB group) or general anesthesia alone (control group). Patient-controlled intravenous analgesia with morphine was initiated immediately upon surgery completion. The primary outcome was the cumulative consumption of morphine within 8 h after surgery. The secondary outcome included postoperative consumptions of morphine at other time points, pain score at rest and during activity, postoperative nausea and vomitting (PONV), and recovery related parameters.Results Totally 30 patients per group were recruited in the study. The 8 h consumption of morphine was lower in the TQLB group than in the control group (median, 0.023 mg/kg vs. 0.068 mg/kg, U=207.5, P<0.001). No significant differences were observed in postoperative pain scores between the two groups. Patients in the TQLB group had fewer episodes of PONV (20% vs. 47%, χ²=4.8, P=0.028) in the first 24 h after surgery and higher scores for quality of recovery (mean, 138.6 vs. 131.9, t=-2.164, P=0.035) 120 h after surgery than the controls.Conclusions TQLB resulted in an opioid-sparing effect during the early postoperative period following LPN, as well as a lower incidence of PONV and improved quality of recovery.     

Improved treatment of systemic blood infections using antibiotics with extracorporeal opsonin hemoadsorption

Here we describe development of an extracorporeal hemoadsorption device for sepsis therapy that employs commercially available polysulfone or polyethersulfone hollow fiber filters similar to those used clinically for hemodialysis, covalently coated with a genetically engineered form of the human opsonin Mannose Binding Lectin linked to an Fc domain (FcMBL) that can cleanse a broad range of pathogens and endotoxin from flowing blood without having to first determine their identity. When tested with human whole blood in vitro, the FcMBL hemoadsorption filter (FcMBL-HF) produced efficient (90–99%) removal of Gram negative (Escherichia coli) and positive (Staphylococcus aureus) bacteria, fungi (Candida albicans) and lipopolysaccharide (LPS)-endotoxin. When tested in rats, extracorporeal therapy with the FcMBL-HF device reduced circulating pathogen and endotoxin levels by more than 99%, and prevented pathogen engraftment and inflammatory cell recruitment in the spleen, lung, liver and kidney when compared to controls. Studies in rats revealed that treatment with bacteriocidal antibiotics resulted in a major increase in the release of microbial fragments or ‘pathogen-associated molecular patterns’ (PAMPs) in vivo, and that these PAMPs were efficiently removed from blood within 2 h using the FcMBL-HF; in contrast, they remained at high levels in animals treated with antibiotics alone. Importantly, cleansing of PAMPs from the blood of antibiotic-treated animals with the FcMBL-hemoadsorbent device resulted in reduced organ pathogen and endotoxin loads, suppressed inflammatory responses, and resulted in more stable vital signs compared to treatment with antibiotics alone. As PAMPs trigger the cytokine cascades that lead to development of systemic inflammatory response syndrome and contribute to septic shock and death, co-administration of FcMBL-hemoadsorption with antibiotics could offer a more effective approach to sepsis therapy.     

心房颤动患者血清心锚重复蛋白的变化及临床意义

目的:探讨血清心锚重复蛋白(CARP)在心房颤动(房颤)中的变化及临床意义。方法:选择房颤组64例和窦性心律(窦律)组60例,采用酶联免疫吸附法(ELISA法)检测入选者血清CARP浓度,并对结果进行统计学分析。结果:房颤组CARP水平高于窦律组[(8.08±1.23)ng/L∶(7.09±1.05)ng/L,P<0.05],持续性房颤亚组CARP水平高于阵发性亚组[(8.24±1.27)ng/L∶(7.83±1.30)ng/L,P<0.05]。结论:房颤患者的血清CARP浓度水平明显增高,血清CARP浓度水平与心房颤动的发生和维持有一定联系。     

Efficacy and Safety of Limertinib (ASK120067) in Patients With Locally Advanced or Metastatic EGFR Thr790Met-Mutated NSCLC: A Multicenter,Single-Arm,Phase 2b Study

IntroductionLimertinib (ASK120067) is a newly developed third-generation EGFR tyrosine kinase inhibitor targeting both sensitizing EGFR and EGFR Thr790Met (T790M) mutations. This study aimed to evaluate the efficacy and safety of limertinib in patients with locally advanced or metastatic EGFR T790M-mutated NSCLC.MethodsThis is a single-arm, open-label, phase 2b study conducted at 62 hospitals across the People’s Republic of China. Patients with locally advanced or metastatic NSCLC with centrally confirmed EGFR T790M mutations in tumor tissue or blood plasma who progressed after first- or second-generation EGFR tyrosine kinase inhibitors or with primary EGFR T790M mutations were enrolled. Patients received limertinib 160 mg orally twice daily until disease progression or unacceptable toxicity. The primary end point was objective response rate (ORR) assessed by independent review committee per the Response Evaluation Criteria in Solid Tumors version 1.1. Secondary end points included disease control rate, progression-free survival (PFS), duration of response (DoR), overall survival, and safety. Safety was assessed according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.03.ResultsFrom July 16, 2019, to March 10, 2021, a total of 301 patients were enrolled and started the treatment of limertinib. All patients entered the full analysis set and safety set. By the data cutoff date on September 9, 2021, 76 (25.2%) remained on treatment. The median follow-up time was 10.4 months (range: 0.3–26.3). On the basis of full analysis set, the independent review committee-assessed ORR was 68.8% (95% confidence interval [CI]: 63.2%–74.0%) and disease control rate was 92.4% (95% CI: 88.8%–95.1%). The median PFS was 11.0 months (95% CI: 9.7–12.4), median DoR was 11.1 months (95% CI: 9.6–13.8), and median OS was not reached (95% CI 19.7 months–not evaluable). Objective responses were achieved across all prespecified subgroups. For 99 patients (32.9%) with central nervous system (CNS) metastases, the ORR was 64.6% (95% CI: 54.4%–74.0%), median PFS was 9.7 months (95% CI: 5.9–11.6), and median DoR was 9.6 months (95% CI: 8.1–15.2). For 41 patients who had assessable CNS lesion, the confirmed CNS-ORR was 56.1% (95% CI: 39.7%–71.5%) and median CNS-PFS was 10.6 months (95% CI: 5.6–not evaluable). In safety set, 289 patients (96.0%) experienced at least one treatment-related adverse event (TRAE), with the most common being diarrhea (81.7%), anemia (32.6%), rash (29.9%), and anorexia (28.2%). Grade ≥3 TRAEs occurred in 104 patients (34.6%), with the most common including diarrhea (13.0%), hypokalemia (4.3%), anemia (4.0%), and rash (3.3%). TRAEs leading to dose interruption and dose discontinuation occurred in 24.6% and 2% of patients, respectively. No TRAE leading to death occurred.ConclusionsLimertinib (ASK120067) was found to have promising efficacy and an acceptable safety profile for the treatment of patients with locally advanced or metastatic EGFR T790M-mutated NSCLC. Clinical Trial information: NCT03502850.     

In vitro antibacterial activity of Western Australian honeys,and manuka honey,against bacteria implicated in impetigo

Impetigo is a contagious skin disease caused by Staphylococcus aureus and Streptococcus pyogenes. Without treatment, impetigo may be recurrent, develop into severe disease, or have serious, life-threatening sequelae. Standard treatment consists of topical or systemic antibiotic therapy (depending on severity), however, due to antibiotic resistance some therapies are increasingly ineffective. In this study we evaluated the potential for honey as an alternative treatment for impetigo. A broth microdilution assay in 96-well microtitre trays was used to determine the minimum inhibitory concentrations (MICs) of six monofloral honeys (jarrah, marri, red bell, banksia, wandoo, and manuka), a multifloral honey and artificial honey against S. aureus (n = 10), S. pyogenes (n = 10), and coagulase-negative staphylococci (CoNS) (n = 10). The optical density (OD) of all microtitre tray wells was also determined before and after assay incubation to analyse whether sub-MIC growth inhibition occurred. Jarrah, marri, red bell, banksia, and manuka honeys were highly effective at inhibiting S. aureus and CoNS, with MIC₅₀ values ranging from 4 to 8% w/v honey. S. pyogenes was also inhibited by these same honeys, albeit at higher concentrations (8–29% w/v). Wandoo and multifloral honeys had the least antibacterial activity with MICs of >30% (w/v) for all isolates. However, OD data indicated that sub-MIC concentrations of honey were still partially restricting bacterial growth. Our pre-clinical data indicate that honey may be a potential therapeutic agent for the routine treatment of mild impetigo, and we suggest that clinical trials would be appropriate to further investigate this.     

A Double-Blind Randomized Placebo-Controlled Phase 3 Trial of Tobramycin Inhalation Solution in Adults With Bronchiectasis With Pseudomonas aeruginosa Infection

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Formin-like 2 promotes angiogenesis and metastasis of colorectal cancer by regulating the EGFL6/CKAP4/ERK axis

Increasing evidence indicates that angiogenesis plays a pivotal role in tumor progression. Formin-like 2 (FMNL2) is well-known for promoting metastasis; however, the molecular mechanisms by which FMNL2 promotes angiogenesis in colorectal cancer (CRC) remain unclear. Here, we found that FMNL2 promotes angiogenesis and metastasis of CRC in vitro and in vivo. The GDB/FH3 domain of FMNL2 directly interacts with epidermal growth factor-like protein 6 (EGFL6). Formin-like 2 promotes EGFL6 paracrine signaling by exosomes to regulate angiogenesis in CRC. Cytoskeleton associated protein 4 (CKAP4) is a downstream target of EGFL6 and is involved in CRC angiogenesis. Epidermal growth factor-like protein 6 binds to the N-terminus of CKAP4 to promote the migration of HUVECs by activating the ERK/MMP pathway. These findings suggest that FMNL2 promotes the migration of HUVECs and enhances angiogenesis and tumorigenesis in CRC by regulating the EGFL6/CKAP4/ERK axis. Therefore, the EGFL6/CKAP4/ERK axis could be a candidate therapeutic target for CRC treatment.     

Comparison of recombinant human FSH biosimilar QL1012 with Gonal-f® for ovarian stimulation: a phase-three trial

Research questionAre QL1012 and Gonal-f® equivalent in women undergoing ovarian stimulation for assisted reproductive technology (ART)?DesignThis multicentre, randomized, assessor-blinded, phase-three trial was conducted at 13 centres in China. Eligible patients were infertile women; age 20–39 years; body mass index 18–30 kg/m²; regular menstrual cycles; and indication for ART. After successful pituitary downregulation, patients were randomly assigned (1:1) to receive QL1012 or Gonal-f®, stratified by age (initial dose of 75–150 IU for women younger than 30 years, 150–225 IU for women aged 30–34 years and 225–300 IU for women aged ≥35 years, subcutaneously, once daily). The primary end point was the number of oocytes retrieved.ResultsBetween October 2018, and June 2019, 341 patients were included in the per-protocol set. The mean numbers of oocytes retrieved were 14.7 ± 7.0 in the QL1012 group (n = 169) and 13.4 ± 6.1 in the Gonal-f® group (n = 172). Adjusted by analysis of covariance model, the least-squares mean difference was 1.3 oocytes (95% CI –0.1 to 2.7; P = 0.0650), within the pre-defined equivalence margins of ±3.0. Similar results were observed in the full analysis set. Additionally, no statistical differences were found in secondary end points except oestradiol concentration (median 3948.0 pg/ml versus 3545.3 pg/ml; P = 0.0015). Ovarian hyperstimulation syndrome (12.4% versus 13.1 %) and other adverse events were similar between the two groups.ConclusionsTherapeutic equivalence and similar safety profiles were demonstrated between QL1012 and Gonal-f® in women undergoing ovarian stimulation for ART.