Bone malignant tumors are diseases that endanger human lives and compromise patients' quality of life. Tumors are conventionally treated via chemotherapy; however, nonspecific damage to healthy cells and inefficient targeting of tumor sites often occur, necessitating the development of an innovative treatment paradigm. In this study, a long-circulating thermosensitive liposome encapsulating DOX-loaded BPQDs was constructed to release drugs via pH/NIR response for photothermal-chemotherapy synergistic treatment of osteosarcoma. Initially, BPQDs were synthesized through liquid-phase exfoliation coupled with a solvothermal reaction. Subsequently, DOX was immobilized onto the BPQD surface via electrostatic interactions to ensure efficient chemotherapeutic drug loading. Ultimately, the high-performance Lip-BPQDs-DOX drug delivery system was fabricated by encapsulating BPQDs-DOX within long-circulating thermosensitive liposomes using a thin-film dispersion-extrusion method. The drug delivery system demonstrates a transition in size from large to small, superior photothermal conversion efficiency, pH/NIR-responsive drug release, favorable ex vivo and in vivo biocompatibility, and liposome-mediated, photothermal-chemotherapeutic synergistic anti-tumor effects. These characteristics offer valuable insights for designing multifunctional nanotherapeutic systems for related tumors like osteosarcoma.

Gout is a disease caused by the deposition of sodium urate (MSU) crystals in the joints and tissues. Colchicine (COL) has become the first-line drug for the treatment of acute gout due to its low price and efficacy. However, colchicine is highly cytotoxic and oral administration is prone to cause severe adverse effects on the gastrointestinal tract, liver and kidney. Therefore, this study aimed to develop a novel dermal delivery formulation for addressing the safety concerns of this drug. The researchers used ethosomes encapsulation technology to improve the skin permeability of COL. In addition, in order to improve the performance of the ethosomes, it was screened and determined that the addition of 1.0-1.5 mg of ceramide III (Cer3) per mL of ethosomes as a modifier could significantly enhance the stability of the ethosomes, Cer3/COL-ethosomes (CCE) were successfully constructed. The CCE was then mixed with a cataplasm matrix to produce a colchicine-carrying CCE cataplasm, which demonstrated the superimposed effect of the advantages of the two dosage forms, the ethosomes and the cataplasm. Compared with the traditional delivery method of COL, this topical formulation is an attractive alternative for the treatment of gout as it can achieve effective blood levels without causing fluctuations in blood levels, and has good efficacy and higher safety profile.

beta-amyloid protein (A(3) deposition and plaque formation are key pathological markers leading to Alzheimer's disease (AD), and effective detection of A beta can help in the diagnosis and treatment of AD. Near-infrared fluorescence (NIRF) imaging has emerged as an advanced technique for A beta detection due to its low cost and convenience. In this study, BPQD@PDA-F nanocomposite consisting of black phosphorus quantum dots (BPQD), polydopamine (PDA) and fluorescent probe F were designed for fluorescence detection and modulation of A beta 42 aggregates. BPQD@PDA-F nanocomposite had a good fluorescence response (emission wavelength > 650 nm, and the fluorescence intensity was significantly increased when combined with A beta 42 aggregates), selectivity, fluorescence stability, and could be used for specific fluorescence imaging of A beta plaques in AD mouse brain slices. Meanwhile, BPQD@PDA-F nanocomposite was a multifunctional nanoplatform that could inhibit A beta 42 aggregates and significantly disaggregate A beta 42 aggregates under near-infrared (NIR) irradiation, reduce the toxicity of A beta 42 aggregates to SH-SY5Y cells. In particular, it could better penetrate the blood-brain barrier (BBB) under NIR irradiation. Therefore, BPQD@PDA-F nanocomposite provided an effective strategy for the detection and modulation of A beta 42 aggregates, which was expected to be used for the diagnosis and treatment of AD.

Uncontrolled bleeding, bacterial infections, and slow healing are challenges in wound treatment. Hence, there is an urgent need to develop multifunctional wound dressing materials that can meet the needs of all stages of wound healing and minimize human injury. This study focuses on the combination of two-dimensional nanomaterials with novel composite sponge wound dressings through the in situ modification technique. Inorganic metal particles were modified on the surface of negatively charged MXene nanosheets, and the resulting MXeneAgNPs nanocomposites were crosslinked to form a dopamine-bacterial cellulose (BC) filamentous gel network, and bacterial cellulose-PDA-MXene-AgNPs composite sponges (BCP-MAg composite sponges) were prepared through low-temperature freeze-drying. During the hemostatic phase, the high density of BCP-MAg composite sponges with high porosity, specific surface area, and excellent fluid-absorbing ability achieved rapid hemostasis. In the subsequent inflammatory phase, BCP-MAg composite sponge combined with photothermal therapy (PTT) down-regulates pro-inflammatory factors (TNF-alpha, IL-6) to reduce inflammation and facilitate the transition to the proliferative phase. During the proliferative phase, BCP-MAg composite sponges promote collagen deposition and re-epithelialization as well as angiogenesis, providing comprehensive support for wound repair and regeneration and accelerating the healing process. During the remodeling phase, the good biocompatibility of BCP-MAg composite sponge helps the wound to heal more naturally during the remodeling phase. Overall, the composite sponge has good biocompatibility, excellent rapid hemostatic properties, strong antimicrobial efficacy, and effective promotion of wound healing.

In diabetic wounds, the presence of hyperglycemia is often accompanied by a persistent inflammatory response, oxidative stress damage, impaired angiogenesis and bacterial infections around the wound, resulting in impaired proliferation of dermal and epidermal cells and impaired skin regeneration in diabetic wounds. To solve the above problems, this study designed a near-infrared (NIR) light-responsive multifunctional poloxamer hydrogel (EGF/PDA-MXene Gel). The Gel is composed of two-dimensional nanomaterials (2D NMs) MXene as the core, modified by polymer, further loaded with epidermal growth factor (EGF), and has antibacterial, antioxidant, photothermal properties. Meanwhile, EGF/PDA-MXene Gel can be used as a drug repository, alleviating the problem of short half-life, and realizing the sustained release of EGF. The NIR photothermal property induces protein denaturation leading to the death of pathogenic bacteria, avoiding the common clinical problem of antibiotic resistance. In addition, EGF/PDA-MXene Gel promotes diabetic chronic wound healing by promoting epidermal regeneration, collagen deposition, angiogenesis, and several other mechanisms. Therefore, the Gel preparation strategies that combine bioactive molecules with 2D NMs, which maintains the activity of EGF while exploiting the antimicrobial advantages of 2D NMs photothermally, provide a new and promising therapeutic approach for accelerating the repair of chronic infected wounds.

Glioma is the most common primary tumor of the nervous system. Conventional diagnostic methods for glioma often involve time-consuming or reliance on externally introduced materials. Consequently, there is an urgent need for rapid and reliable diagnostic techniques. Raman spectroscopy has emerged as a promising tool, offering rapid, accurate, and label-free analysis with high sensitivity and specificity in biomedical applications. In this review, the fundamental principles of Raman spectroscopy have been introduced, and then the progress of applying Raman spectroscopy in biomedical studies has been summarized, including the identification and typing of glioma. The challenges encountered in the clinical application of Raman spectroscopy for glioma have been discussed, and the prospects have also been envisioned.

Constructing heterojunction is a good method to improve electrocatalytic activity because the heterojunctions can modulate the Fermi level and redistribute charges of the catalysts to accelerate electron transfer. In this study, Ni3S2 nanocones were prepared on nickel foam (NF) by hydrothermal synthesis, and FeCoNi LDH/Ni3S2 Schottky heterojunctions were constructed by electrodeposition of FeCoNi LDH nanosheets onto Ni3S2 nanocones. Electrochemical results demonstrate that FeCoNi LDH/Ni3S2/NF is an efficient alkaline OER catalyst, the overpotential is 216 mV at 100 mA cm-2, and it can maintain stable operation for 110 h. The battery voltage of the dual-electrode structure composed of FeCoNi LDH/Ni3S2/NF and NF at 1 M KOH is 1.61 V at 10 mA cm-2. The results of XPS show that the FeCoNi LDH/Ni3S2 Schottky heterojunction optimizes the electronic structure of the interface, accelerating electron transfer. Additionally, the enhanced electric field effect at the tip of Ni3S2 further promotes electron transfer in the heterojunction structure. FeCoNi LDH/Ni3S2 Schottky heterojunction exhibits significant OER activity, which provides a method for synthesizing transition metal heterojunction catalysts with low cost and high activity in the future.

The cell membrane serves as a barrier against the free entry of foreign substances into the cell. Limited by factors such as solubility and targeting, it is difficult for some drugs to pass through the cell membrane barrier and exert the expected therapeutic effect. Two-dimensional nanomaterial (2D NM) has the advantages of high drug loading capacity, flexible modification, and multimodal combination therapy, making them a novel drug delivery vehicle for drug membrane attachment and intracellular transport. By modulating the surface properties of nanocarriers, it is capable of carrying drugs to break through the cell membrane barrier and achieve precise treatment. In this review, we review the classification of various common 2D NMs, the primary parameters affecting their adhesion to cell membranes, and the uptake mechanisms of intracellular transport. Furthermore, we discuss the therapeutic potential of 2D NMs for several major disorders. We anticipate this review will deepen researchers' understanding of the interaction of 2D NM drug carriers with cell membrane barriers, and provide insights for the subsequent development of novel intelligent nanomaterials capable of intracellular transport.

The management of osteosarcoma presents a significant challenge, and the creation of an intelligent synergistic drug delivery system is broadly acknowledged as a promising approach to therapy. Hence, in this study, a temperature-sensitive hydrogel containing DOX-loaded and folic acid-modified BPNSs that can be injected was developed to enable drug release via a pH/NIR response, aimed at synergistic photothermal-chemotherapeutic treatment of osteosarcoma. The active targeting of BPNSs-PEG-FA/DOX involved liquid-phase stripping and electrostatic adsorption, leading to the preparation of the BPNSs-PEG-FA/DOX aqueous dispersion hybrid hydrogel matrix as a BPNSs-PEG-FA/DOX@Hydrogel through a cold method. This composite hydrogel exhibits favorable through-needle properties, superior photothermal conversion efficiency, pH/NIR intelligent responsiveness, and controlled delayed-release drug release capabilities, along with favorable in vitro cellular biocompatibility. It also demonstrates effective in vitro and in vivo active targeting, controlled delayed release, and synergistic photothermal-chemotherapeutic anti-osteosarcoma activity, showing considerable promise for the treatment of superficial tumors such as osteosarcoma.

At present, precious metal Pt-based catalysts are still the most widely used commercially efficient oxygen reduction reaction (ORR) catalysts. However, due to factors such as scarcity of earth content, high cost, and poor durability, they cannot be used on a large scale in industry. In this paper, Mn-based mullite-type oxides LaMn2O5 flake nanocrystals with large specific surface area were prepared as an effective substitute for noble metal-based catalysts by regulating the hydrothermal conditions, and introducing an appropriate amount of graphene oxide (GO) as the C source significantly improved the conductivity of the catalyst. Adjusting the pH range of the precursor solution changes the OH ion concentration in the hydrothermal environment, destroys the oxygen-containing group species in LaMn2O5@GO and promotes O-2 adsorption during ORR, resulting in a half-wave potential of 0.82 V (vs. RHE). The corresponding catalyst was used to assemble a zinc-air battery, achieving a higher open circuit voltage (1.57 V) and power density (160 mW cm(2)) and demonstrating excellent cyclic stability with a reduction in overpotential of only 30 mV after 450 h of long-term charge-discharge measurement. This work represents a general method to improve the catalytic activity of Mn-based mullite-type oxides for zinc-air battery applications.

With the increasing applications of traditional Chinese medicines worldwide, authenticity identification and quality control are significant for them to go global. Licorice is a kind of medicinal material with various functions and wide applications. In this work, colorimetric sensor arrays based on iron oxide nanozymes were constructed to discriminate active indicators in licorice. Fe2O3, Fe3O4, and His-Fe3O4 nanoparticles were synthesized by a hydrothermal method, possessing excellent peroxidase-like activity that can catalyze the oxidation of 3,3 ',5,5' -tetramethylbenzidine (TMB) in the presence of H2O2 to produce a blue product. When licorice active substances were introduced in the reaction system, they showed competitive effect on peroxidase-mimicking activity of nanozymes, resulting in inhibitory effect on the oxidation of TMB. Based on this principle, four licorice active substances including glycyrrhizic acid, liquiritin, licochalcone A, and isolicoflavonol with the concentration ranging from 1 mu M to 200 mu M were successfully discriminated by the proposed sensor arrays. This work supplies a low cost, rapid and accurate method for multiplex discrimination of active substances to guarantee the authenticity and quality of licorice, which is also expected to be applied to distinguish other substances.

生理时间序列也称生理信号，是按照时间顺序收集的某个生命体征指标的观测结果，如心电信号、呼吸信号。对生理信号的分析可通过提取时域特征、频域特征、时频域特征来实现。此外，生理信号被证明具有广泛的非线性动力学特征，提取生理信号的非线性特征，有利于充分刻画生理信号的变化规律，尤其适用于波形和振幅特征不太明显的情况。

Ethnopharmacological relevance: Erhuang Quzhi Granules (EQG) is a compound composed of 13 traditional Chinese medicines developed by the First Affiliated Hospital of Shihezi University. In clinical practice, EQG has been applied to the treatment of hyperlipidemia and non-alcoholic fatty liver disease (NAFLD), and could significantly improve the serum biochemical indicators of NAFLD patients.Aim of the study: This study aims to explore the bioactive compounds, potential targets, and molecular mecha-nisms of EQG against NAFLD through network pharmacology, molecular docking, and experimental verification.Materials and methods: The chemical components of EQG came from the literature and quality standard. Bioactive compounds were screened based on the absorption, distribution, metabolism, and excretion (ADME) feature, and their potential targets were predicted using the substructure-drug-target network-based inference (SDTNBI). The core targets and signaling pathways were obtained through the analysis of protein-protein interaction (PPI), gene ontology (GO) function, and Kyoto encyclopedia of genes and genomes (KEGG) pathway. The results were further confirmed by literature retrieval, molecular docking, and in vivo experiments. Results: The results of network pharmacology showed 12 active ingredients and 10 core targets for EQG in treating NAFLD. And EQG mainly regulates lipid and atherosclerosis-related pathways to improve NAFLD. The collected literature verified the regulatory effect of the active components of EQG on core targets TP53, PPARG, EGFR, HIF1A, PPARA, and MTOR. Molecular docking results showed that Aloe-Emodin (AE), Emodin, Physcion, and Rhein (RH) had stable binding structures with the core targets HSP90AA1. In vivo experiment showed that AE and RH reduced aspartate transaminase (AST), alanine aminotransferase (ALT), interleukin (IL)-1 beta, IL-6, IL18, and tumor necrosis factor alpha (TNF-alpha) in the serum or liver of NAFLD mice, improved liver lipid deposi-tion and fibrosis, and inhibit gene expression of nuclear factor kappa B (NF-kappa B), NOD-like receptor thermal protein domain associated protein 3 (NLRP3), IL-1 beta, TNF-alpha and protein expression of HSP90, NF-kappa B and Cleaved caspase-1.Conclusions: This study comprehensively revealed the biological compounds, potential targets, and molecular mechanisms of EQG in the treatment of NAFLD, providing a reference basis for the promotion of EQG in the clinic.

临床研究的结局往往与多个因素相关，因此在统计分析中，经常会用到多因素分析的方法。常见的回归分析方法有多重线性回归、Logistic回归、Cox回归以及Poisson回归。本文将对不同回归分析方法的适用场景进行简要介绍，以帮助临床研究者正确选择回归分析方法。

生物药剂学与药物动力学属于综合性学科，承担药物剂型因素、药物效应、用药对象生物特点三者关系的阐明功 能。该学科开展的重要目的是准确评估药物的质量，基于药物特点设计科学合理剂型、生产工艺、药物处方，为临床 合理、科学用药提供对应的科学依据。从学科角度看，生物药剂学与药物动力学属于药剂学分支学科，也是药物制剂 以及药学等多种专业的必备专业课，是医学院重要的课程之一。但该学科囊括大量的药学知识，学生学习时间有限， 加上学习内容以理论为主，所以学生学习的积极性普遍不高，多数人都是通过死记硬背来掌握相应知识，不能将所学 知识转变为自己的技能。在这种学习模式下，专业知识固然重要，但缺乏较强的实践操作能力，学生无法将所学知识 转化为药学技能，即便能够应对学校的理论考试，整体能力却难以保障。基于这一情况，积极分析生物药剂学与药物 动力学课程教学的现状与教学内容特点，积极制定符合实际情况的教学对策，改进现有的教学方法及教学质量，是很 有必要的。本文主要分析生物药剂学与药物动力学的两个教学问题，教学内容及教学课时不匹配与课程考核方式单 一，针对问题探讨教学对策。

Food quality control is essential in industry and daily life. In this work, we developed a novel colorimetric sensor array composed of several pH-sensitive dyes for monitoring meat freshness. A color change in the sensor array was seen after exposure to volatile organic compounds (VOCs), and the images were captured for precise quantification of the VOCs. In conjunction with pattern recognition, meat freshness at different storage periods was readily discerned, revealing that the as-fabricated colorimetric sensor array possessed excellent discrimination ability. The linear range for quantitative analysis of volatiles related to meat spoilage was from 5 ppm to 100 ppm, with a limit of detection at the ppb level (S/N = 3). Furthermore, the testing results obtained by the sensor in assessing meat freshness were validated by a standard method for measuring the total volatile basic nitrogen (TVB-N). The sensing signals showed good agreement with the results obtained in TVB-N when measuring real food samples. The sensor also displayed good reproducibility (RSD < 5%) and long-term stability. The sensor was successfully used for on-site and real-time determination of volatiles emitted from rotting meat, demonstrating its potential application in monitoring the quality and safety of meat products.

常用的统计分析方法往往要求数据是独立的，即2条数据不会互相影响，但在临床研究中经常会有非独立数据，如住院期间多次血常规测量记录、1例患儿的2次住院记录，前后几次的记录可能存在相关性。如果用传统的方法，只能保留1个病例的1次记录，会损失较多信息；有选择地删除某记录则可能造成偏倚。为避免数据损失和偏倚，下面介绍几种非独立数据常用的分析方法。

目的 探讨新型冠状病毒肺炎(COVID?19)对住院成人T1DM患者血糖控制的影响.方法 选取2019年1月至2021年1月于北京大学第三医院内分泌科住院的成人T1DM患者106例.以疫情发生前、后1年为时间界限,分为疫情前组(n=64)和疫情后组(n=42),分析比较两组年龄、性别、DM病程、身高、体重、BP、FPG、HbA1c、血脂、肝功能等,以及DKA发生率及住院期间Ins用量差异.结果 疫情后组HbA1c水平、DKA发生率高于疫情前组[(11.2±2.86)％vs(10.1±2.62)％,24％vs 6％,P<0.05].疫情前后每日Ins用量差异无统计学意义(P>0.05).结论 在COVID?19疫情流行期间,住院成人T1DM患者血糖控制较差,DKA发生风险较高.

To enhance the catalytic activity of two-dimensional layered materials as versatile materials, the modification of transition metal dichalcogenide nanosheets such as MoS2 by doping with heteroatoms has drawn great interests. However, few reports are available on the study of the enzyme-like activity of doped MoS2. In this study, a facile in situ hydrothermal method for the preparation of various ultrathin transition metals (Fe, Cu, Co, Mn, and Ni) doped MoS2 nanosheets has been reported. Through the density functional theory (DFT) and steady-state kinetic analysis, the Co-doped MoS2 nanosheets exhibited the highest peroxidase-like catalytic activity among them. Furthermore, a typical colorimetric assay for H2O2 was presented based on the catalytic oxidation of colorless 3,3′,5,5′-tetramethylbenzidine (TMB) to a blue product (oxTMB) by Co-MoS2. The proposed colorimetric method showed excellent tolerance under extreme conditions and a broad linear range from 0.0005 to 25 mM for H2O2 determination. Concerning the practical application, in situ detection of H2O2 generated from SiHa cells was also fulfilled, fully confirming the great practicability of the proposed method in biosensing fields.

背景 学位论文的质量日益受到重视,全面保证论文质量迫在眉睫.医学研究生学位论文常涉及临床研究的内容,其中临床研究方法学的问题需引起重视.目的 剖析某大学盲审前初审的医学研究生学位论文初稿临床研究方法学论述中存在的常见问题,为规范研究生论文的撰写和自查、提升医学学位论文质量提供参考.方法 北京大学第三医院临床流行病学研究中心于2019—2020年对某校2019届临床医学生内部初审阶段毕业论文的方法学部分进行评审,共包括47篇临床观察性研究.参考STROBE声明清单条目,提取学位论文临床研究方法学关键要素,逐条编码、归类形成文字评阅意见数据库,总结其常见问题并探索解决办法.结果 临床医学研究生学位论文初稿在方法部分常见问题体现在统计方法描述不完整、研究对象代表性不足或纳入排除标准不完整、缺少样本量估算方法或样本量不足等方面,其次是题目模糊不确切、摘要中对背景和选题的意义阐述不明确、结果描述研究对象特征不准确、结果展示不充分、统计图表欠规范等,最后讨论部分未概括与研究目标有关的主要结果,其他问题包括写作结构规范欠佳,伦理易忽视.结论 提升临床医学学位论文质量除了加强对研究生临床科研方法学的培训,有必要制定清晰明确的《医学研究生课题结题阶段学位论文自查清单》,帮助研究生完善论文撰写和导师对学位论文进行审阅把关.