Objective:To compare the therapeutic efficacy between femoral neck system (FNS) and cannulated compression screws (CCS) in the fixation of femoral neck fractures in the elderly patients aged 65 to 75 years old.Methods:A retrospective study was conducted to analyze the data of 39 patients aged 65 to 75 years old who had been treated for femoral neck fractures at Department of Trauma Surgery, Hospital Affiliated to Qingdao University from January 2015 to September 2022. The patients were divided into 2 groups according to their internal fixation methods. In the FNS group of 18 cases subjected to FNS fixation, there were 8 male and 10 females with an age of (71.1±2.8) years. In the CCS group of 21 cases subjected to CCS fixation, there were 7 males and 14 females with an age of (70.1±2.9) years. The 2 groups were compared in terms of intraoperative fluoroscopy frequency, surgical time, intraoperative bleeding, hospitalization costs, fracture healing time, internal fixation failure, and Harris hip score, changes in neck shaft angle, and femoral neck shortening at 1 year after surgery.Results:The differences were not statistically significant in the preoperative general data or follow-up time between the 2 groups, indicating comparability ( P>0.05). In the FNS group, the intraoperative fluoroscopy frequency [(15.1±2.3) times] was significantly lower than that in the CCS group [(19.5±3.5) times], the surgical time [(49.2±5.2) minutes] was significantly shorter than that in CCS group [(62.4±11.2) minutes], and the intraoperative bleeding [(74.2±15.6) mL] and hospitalization costs [(39,928.7±1,438.3) yuan] were significantly higher than those in the CCS group [(53.1±17.3) mL and (23,527.9±2,126.3) yuan] (all P<0.05). The difference in fracture healing time was not statistically significant between the 2 groups ( P>0.05). In the FNS group, the decreased neck shaft angle (2.65°±1.66°) and femoral neck shortening (3.9±1.3 mm) were significantly smaller than those in the CCS group [4.18°±2.13° and (6.3±2.5) mm] at 1 year after surgery, and the Harris hip score [(82.2±7.2) points] was significantly higher than that in the CCS group [(76.4±5.9) points] (all P<0.05). Internal fixation failure occurred in 1 case in the FNS group and in 4 cases in the CCS group, respectively, showing no statistically significant difference ( P>0.05). Conclusions:Compared with CCS fixation, FNS fixation may lead to better therapeutic efficacy in patients with femoral neck fracture aged 65 to 75 years old. However, the risk of internal fixation failure should also be taken into consideration.

A novel amide alkaloid,bursatamide A(1),featuring an unprecedented propyl-hexahydronaphthalene carbon frame-work,was isolated from the infrequently studied sea hare Bursatella leachi,alongside a new 3-phenoxypropanenitrile alkaloid,bursatellin B(2),and twelve known compounds.The structures of 1 and 2 were elucidated through comprehensive spectroscopic data analyses,while their relative and absolute configurations(ACs)were established through total synthesis and a series of quantum chem-ical calculations,including calculated electronic circular dichroism(ECD)spectra,optical rotatory dispersion(ORD)methods,and DP4+probability analyses.Bursatamide A(1)demonstrated inhibitory effects against the human pathogenic bacteria Listeria monocyt-ogenes and Vibrio cholerae.Erythro-bursatellin B(21),a diastereoisomer of 2,exhibited notable antibacterial activity against the fish pathogenic bacterium Streptococcus parauberis FP KSP28,with an MIC90 value of 0.0472 μg·mL-1.

Due to the limitations of current anti-HBV therapies, the HBV core (HBc or HBcAg) protein assembly modulators (CpAMs) are believed to be potential anti-HBV agents. Therefore, discovering safe and efficient CpAMs is of great value. In this study, we established a HiBiT-based high-throughput screening system targeting HBc and screened novel CpAMs from an in-house marine chemicals library. A novel lead compound 8a, a derivative of the marine natural product naamidine J, has been successfully screened for potential anti-HBV activity. Bioactivity-driven synthesis was then conducted, and the structure‒activity relationship was analyzed, resulting in the discovery of the most effective compound 11a (IC₅₀ = 0.24 μmol/L). Furthermore, 11a was found to significantly inhibit HBV replication in multiple cell models and exhibit a synergistic effect with tenofovir disoproxil fumarate (TDF) and IFNa2 in vitro for anti-HBV activity. Treatment with 11a in a hydrodynamic-injection mouse model demonstrated significant anti-HBV activity without apparent hepatotoxicity. These findings suggest that the naamidine J derivative 11a could be used as the HBV core protein assembly modulator to develop safe and effective anti-HBV therapies.

Endosomal TLRs (TLR3/7/8/9) are highly analogous innate immunity sensors for various viral or bacterial RNA/DNA molecular patterns. Among them, TLR7, in particular, has been suggested to be a target for various inflammatory disorders and autoimmune diseases including systemic lupus erythematosus (SLE); but few small-molecule inhibitors with elaborated mechanism have been reported in literature. Here, we reported a well-characterized human TLR7-specific small-molecule inhibitor, TH-407b, with promising potency and negligible cytotoxicity through a novel binding mechanism. Notably, TH-407b not only effectively inhibited TLR7-mediated pro-inflammatory signaling in a variety of cultured cell lines but also demonstrated potent inflammation suppressing activities in primary peripheral blood mononuclear cells (PBMCs) derived from SLE patients. Furthermore, TH-407b showed prominent efficacy in vivo, improved survival rate and ameliorated symptoms of SLE model mice. To obtain molecular insights into the TH-407b derivatives' inhibition mechanism, we performed the structural analysis of TLR7/TH-407b complex using cryogenic electron microscopy (cryo-EM) method. As an atomistic resolution cryo-EM structure of the TLR family, it not only of value to facilitate structure-based drug design, but also shed light to methodology development of small proteins using EM. Significantly, TH-407b has unveiled an inhibition strategy for TLR7 via stabilizing its resting/inactivated state. Such a resting state could be generally applicable to all TLRs, rendering a useful method for targeting this group of important immunological receptors.

Since the 21st century, with the rapid development of biomedicine, research and discussion on human-animal chimerism technology have attracted wide attention. The general research of human-animal chimeras is to introduce human stem cells into animal embryos that remove organ genes, aiming to cultivate human organs in human-animal chimeras to solve the shortage of human organ donors and provide experimental materials for the development of related scientific research. However, due to its technology involves cross-species genetic modification, which destroys the species boundary and the naturalness of ecological niche, it has caused various ethical issues such as threatening species safety and harming human dignity. The development of human-animal chimerism technology is the choice of the times for technological progress, with its inevitability and rationality. It should not be absolutely prohibited, but must abide by the ethical principles such as safety, benefit, respect, and justice, and operate harmoniously under strict and orderly ethical norms.

Summary: Structural nasal obstruction（SNO） is a series of diseases caused by congenital or acquired structural anatomical abnormalities of nasal airway and its surrounding tissues, which leads to increased nasal ventilation resistance. The effect of medication drugs for SNO is poor and surgical intervention is often needed. However, the abnormal structure of nasal airway is very complex, including the periphery of nasal airway, internal nasal airway, the front and rear of nasal airway and complex factors. These abnormal structures may interfere with the nasal airflow mechanics by changing the nasal ventilation volume and disrupting the symmetry of the bilateral nasal cavity, and finally lead to subjective feeling of nasal obstruction. In addition, the structure of nasal airway has plasticity. After the abnormal structure appears, the corresponding compensation of nasal airway can occur to ensure normal nasal ventilation and bilateral nasal cavity symmetry. Therefore, the SNO is the result of the failure of nasal airway remodeling after the appearance of abnormal structures. The etiology of SNO is complex, involving original structural abnormalities, nasal symmetry changing and nasal airway structure remodeling. Therefore, accurate identification of the main factors leading to SNO is the vitalpremise of making personalized nasal ventilation surgery.

N

Objective To compare the clinical outcomes between open reduction and fixation with cannulated screws via the modified Burks-Schaffer approach versus arthroscopic EndoButton plating for avulsion fracture of the tibial attachment of the posterior cruciate ligament(PCL).Methods From February 2013 to August 2017,41 patients with acute displaced avulsion fracture of the tibial PCL attachment were treated operatively at Department of Trauma Surgery,The Affiliated Hospital to Qingdao University.They were 24 men and 17 women,aged from 18 to 65 years (average,39 years).The lefi knee was injured in 22cases and the right knee in 19.They were divided into 2 groups according to their different fixation methods.The open reduction and fixation group (23 cases) received open reduction and fixation with cannulated screws via the modified Burks-Schaffer approach while the arthroscopic group (18 cases) arthroscopic Endobutton plating.The 2 groups were compared in terms of operation time,bleeding,objective knee scores and knee range of motion (ROM) after operation.Results All the 41 patients were followed up from 23 to 40months (average,27.2 months).Their follow-up revealed no incision infection,malunion,nonunion or loosening of the implants.Their knee X-ray films at the final follow-ups showed bony union of all the avulsion fractures.There were significant differences between the open reduction and fixation group and the arthroscopic group in operation time (52.6±7.3 min versus 86.8±9.2 min) and bleeding (63.9±12.7 mL versus 19.7 ± 10.2 mL) (P ＜ 0.05).There was no significant difference in the objective knee scores or knee ROM between the 2 groups (P ＞ 0.05).Conclusions Both open reduction and cannulated screw fixation via the modified Burks-Schaffer approach and arthroscopic EndoButton plating can achieve satisfactory clinical outcomes in the treatment of avulsion fracture of the tibial PCL attachment.Although the 2 methods make no significant differences in stability of the knee joint or in clinical scores,the latter leads to less bleeding and the former shorter operation time.

Marine sponges of the genus are well known as rich sources of diverse and complex biologically relevant natural products, including alkaloids, terpenoids, peptides, lipids, and steroids. Some of these metabolites, with novel structures and promising biological activities, have attracted a lot of attention from chemists seeking to perform their total synthesis in parallel to intensive biological studies towards new drug leads. In this review, we summarized the distribution of the chemically investigated sponges, the isolation, synthesis and biological activities of their secondary metabolites, covering the literature from 1982 to early 2018.

Fifty-two methyl xestospongoate analogues were designed, synthesized and evaluated for the antiproliferative activity. Starting from alkynyl methyl ester and diyne, methyl xestospongoate analogues 4(a-m)-7(a-m)were synthesized by Cadiot-Chodkiewitz coupling and Sonogashira coupling reactions. Their structures were identified by 1H NMR, 13C NMR and HREI-MS. The cytotoxic inhibiton activities in vitro of some compounds were evaluated against human cancer cells A549 and P-388 by a CCK-8 method. Among them, compound 6k exhibited potent cell growth inhibitory activity against A549 and P-388 cancer cells, with IC50 values of 9. 36 and 9. 62 μmol/L, respectively.