Distinct from the complementary inhibition mechanism through binding to the target with three-dimensional conformation of small molecule inhibitors, targeted protein degradation technology takes tremendous advantage of endogenous protein degradation pathway inside cells to degrade plenty of “undruggable” target proteins, which provides a novel route for the treatment of many serious diseases, mainly including proteolysis-targeting chimeras, lysosome-targeting chimeras, autophagy-targeting chimeras, antibody-based proteolysis-targeting chimeras, etc. Unlike proteolysis-targeting chimeras first found in 2001, which rely on ubiquitin-proteasome system to mainly degrade intracellular proteins of interest, lysosome-targeting chimeras identified in 2020, which was act as the fastly developing technology, utilize cellular lysosomal pathway through endocytosis mediated by lysosome-targeting receptor to degrade both extracellular and membrane proteins. As an emerging biomedical technology, nucleic acid-driven lysosome-targeting chimeras utilize nucleic acids as certain components of chimera molecule to replace with ligand to lysosome-targeting receptor or protein of interest, exhibiting broad application prospects and potential clinical value in disease treatment and drug development. This review mainly introduced present progress of nucleic acid-driven lysosome-targeting chimeras technology, including its basic composition, its advantages compared with antibody or glycopeptide-based lysosome-targeting chimeras, and focused on its chief application, in terms of the type of lysosome-targeting receptors. Most research about the development of nucleic acid-driven lysosome-targeting chimeras focused on those which utilized cation-independent mannose-6-phosphonate receptor as the lysosome-targeting receptor. Both mannose-6-phosphonate-modified glycopeptide and nucleic aptamer targeting cation-independent mannose-6-phosphonate receptor, even double-stranded DNA molecule moiety can be taken advantage as the ligand to lysosome-targeting receptor. The same as classical lysosome-targeting chimeras, asialoglycoprotein receptor can also be used for advance of nucleic acid-driven lysosome-targeting chimeras. Another new-found lysosome-targeting receptor, scavenger receptor, can bind dendritic DNA molecules to mediate cellular internalization of complex and lysosomal degradation of target protein, suggesting the successful application of scavenger receptor-mediated nucleic acid-driven lysosome-targeting chimeras. In addition, this review briefly overviewed the history of lysosome-targeting chimeras, including first-generation and second-generation lysosome-targeting chimeras through cation-independent mannose-6-phosphonate receptor-mediated and asialoglycoprotein receptor-mediated endocytosis respectively, so that a clear timeline can be presented for the advance of chimera technique. Meantime, current deficiency and challenge of lysosome-targeting chimeras was also mentioned to give some direction for deep progress of lysosome-targeting chimeras. Finally, according to faulty lysosomal degradation efficiency, more cellular mechanism where lysosome-targeting chimeras perform degradation of protein of interest need to be deeply explored. In view of current progress and direction of nucleic acid-driven lysosome-targeting chimeras, we discussed its current challenges and development direction in the future. Stability of natural nucleic acid molecule and optimized chimera construction have a great influence on the biological function of lysosome-targeting chimeras. Discovery of novel lysosome-targeting receptors and nucleic aptamer with higher affinity to the target will greatly facilitate profound advance of chimera technique. In summary, nucleic acid-driven lysosome-targeting chimeras have many superiorities, such as lower immunogenicity, expedient synthesis of chimera molecules and so on, in contrast to classical lysosome-targeting chimeras, making it more valuable. Also, the chimera technology provides new ideas and methods for biomedical research, drug development and clinical treatment, and can be used more widely through further research and optimization.

The chemical constituents in dried roots of Atractylodes macrocephala were investigated in this study. Through utilizing normal-phase silica gel and ODS column chromatography, TLC, and semi-preparative HPLC, 4 new sesquiterpenoids were purified from the ethyl acetate extract of A. macrocephala. By various spectroscopic techniques, such as 1D and 2D NMR, HR-ESI-MS, IR, UV, and CD, their structures were identified as atractylmacron A (1), 9β-hydroxyasterolide (2), atractylenolide H (3), atractylenolide J (4). Compound 1 possesses a rare 6/7 bicyclic skeleton.

Objective To investigate the distribution and antimicrobial resistance profiles of clinically isolated Haemophilus influenzae and Moraxella catarrhalis in hospitals across China from 2015 to 2021,and provide evidence for rational use of antimicrobial agents.Methods Data of H.influenzae and M.catarrhalis strains isolated from 2015 to 2021 in CHINET program were collected for analysis,and antimicrobial susceptibility testing was performed by disc diffusion method or automated systems according to the uniform protocol of CHINET.The results were interpreted according to the CLSI breakpoints in 2022.Beta-lactamases was detected by using nitrocefin disk.Results From 2015 to 2021,a total of 43 642 strains of Haemophilus species were isolated,accounting for 2.91％of the total clinical isolates and 4.07％of Gram-negative bacteria in CHINET program.Among the 40 437 strains of H.influenzae,66.89％were isolated from children and 33.11％were isolated from adults.More than 90％of the H.influenzae strains were isolated from respiratory tract specimens.The prevalence of β-lactamase was 53.79％in H.influenzae strains.The H.influenzae strains isolated from children showed higher resistance rate than the strains isolated from adults.Overall,779 strains of H.influenzae did not produce β-lactamase but were resistant to ampicillin(BLNAR).Beta-lactamase-producing strains showed significantly higher resistance rates to these antimicrobial agents than the β-lactamase-nonproducing strains.Of the 16 191 M.catarrhalis strains,80.06％were isolated from children and 19.94％isolated from adults.M.catarrhalis strains were mostly susceptible to both amoxicillin-clavulanic acid and cefuroxime,evidenced by resistance rate lower than 2.0％.Conclusions The emergence of antibiotic-resistant H.influenzae due to β-lactamase production poses a challenge for clinical anti-infective treatment.Therefore,it is very important to implement antibiotic resistance surveillance for H.influenzae and guide rational antibiotic use.All local clinical microbiology laboratories should actively improve antibiotic susceptibility testing and strengthen antibiotic resistance surveillance for H.influenzae.

Objective:To explore the safety, economic benefits, and clinical application effect of the new practical patent open window central venous catheter combination dressing (Patent No.ZL 202121652858.8).Methods:From October 2022 to October 2023, a randomized controlled trial was conducted. A total of 120 tumor patients in Yunnan Cancer Hospital with indwelling central venous catheters who met the inclusion and exclusion criteria were randomly divided into three groups at a ratio of 1∶1∶1 with random digit table, with 40 patients in each group: control group 1, control group 2, and the experimental group. In control group 1, Smith & Nephew IV 3000 dressing was used, in control group 2, 3M transparent dressing was used; and in the experimental group, the self - developed fenestrated central venous catheter combined dressing by the researchers was used for catheter maintenance. The skin surface bacterial colonization, the occurrence of medical adhesive-related skin injuries, catheter maintenance time, and maintenance costs were compared among the three groups.Results:In control group 1, there were 21 males and 19 females, with an average age of (51.53 ± 12.01) years. In control group 2, there were 22 males and 18 females, with an average age of (54.00 ± 11.03) years. In the experimental group, there were 19 males and 21 females, with an average age of (53.60 ± 9.41) years. During the 72 - hour observation period, 1, 3, and 2 cases of bacterial colonization occurred in control group 1, control group 2, and the experimental group respectively, and there was no significant difference among the three groups ( χ2 = 1.10, P = 0.577). No medical adhesive - related skin injury occurred in the experimental group, and there was a significant difference compared with the 4 cases in control group 2 ( χ2 = 4.21, P = 0.040). The average catheter maintenance time and maintenance cost in the experimental group were (15.20 ± 1.56) minutes and (8.11 ± 1.35) yuan respectively. Compared with (21.05 ± 3.31) minutes and (13.16 ± 1.03) yuan in control group 1, the differences were statistically significant ( t = 5.85, 5.05, both P<0.001). Compared with (21.08 ± 3.00) minutes and (15.17 ± 1.63) yuan in control group 2, the differences were also statistically significant ( t = 5.88, 7.06, both P<0.001). Conclusions:The open-window central venous catheter combination dressing designed in this study can effectively reduce the incidence of medical adhesive-related skin injury, and also has a better role in saving maintenance time and reducing maintenance costs, especially for patients who need repeated dressing changes at the puncture point for treatment with the advantages of, convenience, economy, speed, firm fixation and safety.

Objective:To investigate factors influencing frequent episodes (≥ 4 episodes within 1 year) in children with moderate-to-severe atopic dermatitis (AD) in China.Methods:A national multicenter cross-sectional study was conducted. Patients under the age of 18 years diagnosed with moderate-to-severe AD were enrolled at dermatology clinics in 18 medical institutions across 12 provinces and municipalities in China between June 12 and August 8, 2023. At the time of the visit, their guardians completed a structured questionnaire covering demographic characteristics, clinical features of AD, personal and family history, factors associated with frequent episodes of moderate-to-severe AD, compliance with treatment, and disease awareness. Statistical analyses included t tests, one-way analysis of variance, rank-sum tests, and chi-square tests, with multiple-response analysis applied for multiple-choice questions. Results:A total of 965 valid questionnaires were collected, and 965 children with moderate-to-severe AD were included. Among them, there were 531 males and 434 females, 678 (70.3%) were aged 2 - < 12 years, 837 (86.7%) were from urban areas, the age at onset was 2.47 ± 3.03 years, and the median frequency of AD episodes in the past year was 4 times. These children were divided into 2 groups based on the median episode frequency: < 4-episode group (439 cases, 45.5%) and ≥ 4-episode group (526 cases, 54.5%). Compared with the < 4-episode group, children in the ≥ 4-episode group showed younger ages at onset (2.22 ± 2.98 years vs. 2.76 ± 3.06 years, P = 0.006) and higher proportions of patients with comorbid allergic diseases in both the children themselves (82.9% [436/526] vs. 69.7% [306/439], χ2 = 23.42, P < 0.001) and their relatives (66.0% [347/526] vs. 57.4% [252/439], χ2 = 7.46, P = 0.006). Children in the ≥ 4- episode group also had higher monthly usage of moisturizers (150 [30, 300] g vs. 60 [6, 200] g) and daily frequency of moisturizer use, greater disease awareness, but more severe fear of medication use (all P < 0.05). The region and the human development index level were both significantly associated with the episode frequency (both P < 0.001), with the highest proportion of children from South China in the ≥ 4- episode group (36.3%, 191/526). Children in the ≥ 4-episode group also had a longer duration of topical glucocorticoid use than those in the < 4-episode group ( Z = -2.21, P = 0.027). External triggers associated with AD episodes mainly included heat exposure (50.36%, 486/965), hot water bathing (40.73%, 393/965), seafood (23.52%, 227/965), and dust mites (33.37%, 322/965) . Conclusion:In children with moderate-to-severe AD in China, factors influencing frequent episodes may include residence in southern or economically developed regions, earlier age at onset, having a personal or family history of allergic diseases, and fear of medication use.

OBJECTIVE: To investigate the clinical efficacy and advantages of robot-assisted total knee arthroplasty (TKA) in patients with varus knee osteoarthritis. METHODS: Between October 2022 and June 2023, a total of 59 patients with severe knee osteoarthritis resulting in varus were treated with total knee arthroplasty, aged from 59 to 81 years with an average (70.90±4.63) years, including 19 mals and 40 females. The patients were divided into two groups based on the surgical method used:28 patients in the robot group and 31 patients in the traditional group. The robot group consisted of 8 males and 20 femalse patients, with an average age of (70.54±4.80) years and an average disease duration of (14.89±8.72) months. The traditional group consisted of 11 males and 20 females patients, with an average age of (71.39±4.5) years and an average disease duration of (12.32±6.73) months. The operative duration, amount of bleeding during the operation, postoperative activity time after the operation, hip-knee-ankle angle (HKA), lateral distal femoral angle (LDFA), medial proximal tibial angle (MPTA), and complications were compared between the two groups before and after the operation. Lateral tibia component (LTC), frontal tibia component (FTC), frontal femoral component (FFC) and lateral femoral component (LFC) were measured 6 months after operation Additionally, the degree of knee joint motility, American Knee Society score (KSS), and visual analogue scale(VAS) were compared before and after the operation. RESULTS: All patients had gradeⅠwound healing without any complications, and all patients were followed up for 6 to 8 months, with an average of (6.5±1.5) months. There were no significant differences preoperative imaging evaluation indexes (including HKA, LDFA, and MPTA), preoperative knee mobility, preoperative VAS, and preoperative KSS between the two groups (P>0.05). Comparing the operation time (109.11±7.16) min vs. (83.90±7.85) min, length of the incision (16.60±2.33) cm vs. (14.47±1.41) cm, intraoperative bleeding (106.93±6.15) ml vs. (147.97±7.62) ml, postoperative activity time (17.86±1.84) h vs. (21.77±2.68) h, between the two groups showed statistically significant differences (P<0.05). There were significant differences in FFC (88.96±0.84)° vs. (87.93±1.09)° and LFC (88.57±1.10)° vs. (87.16±1.2)° between the two groups at 6 months after operation (P<0.05). The robotic group 1, 3, 6 months after KSS (75.96±3.96), (81.53±3.78), (84.50±3.29) scores, VAS (3.68±0.67), (2.43±0.79), (0.54±0.64), knee joint mobility (113.32±4.72) °, (123.93±3.99) °, (135.36±2.34) °;Traditional group KSS (73.77±4.18), (76.48±3.60), (80.19±3.28) scores, VAS (4.16±1.04), (3.03±0.75), (1.42±0.76) scores, knee joint mobility (109.19±6.95) °, (119.94±6.08) °, (134.48±2.14) °. Compared to before surgery, both groups showed significant improvement in KSS, VAS and knee mobility during the three follow-up visits (P<0.001). Additionally, postoperative HKA (180.39±1.95)° vs. (178.52±2.23)°, LDFA (89.67±0.63) ° vs. (89.63±0.63)°, and MPTA (89.44±0.55)° vs. (89.29±0.60)° were significantly improved in both groups compared to before surgery (P<0.001). The robotic group had higher KSS than the traditional group at 1, 3, and 6 months after surgery (P<0.05). The robotic group also had lower VAS than the traditional group at 1, 3, and 6 months after surgery (P<0.05). Furthermore, knee mobility was higher in the robotic group than those in the traditional group at 1 and 6 months after surgery (P<0.05), but there was no significant difference between the two groups at 6 months after surgery. CONCLUSION Robot-assisted total knee arthroplasty is a safe and effective method for total knee replacement. The use of robotics can improve the limb axis and prosthesis alignment for patients with preoperative varus deformity, resulting in better clinical and imaging outcomes compared to the conventional group.
Humans ; Female ; Male ; Arthroplasty, Replacement, Knee/methods* ; Aged ; Middle Aged ; Osteoarthritis, Knee/physiopathology* ; Aged, 80 and over ; Robotic Surgical Procedures/methods*

To guide clinical blood transfusion practices for pediatric patients, the National Health Commission has issued the health standard "Guideline for pediatric transfusion" (WS/T 795-2022). Blood transfusion is one of the most commonly used supportive treatments for children with hematological diseases. This guideline provides guidance and recommendations for blood transfusions in children with aplastic anemia, thalassemia, autoimmune hemolytic anemia, glucose-6-phosphate dehydrogenase deficiency, acute leukemia, myelodysplastic syndromes, immune thrombocytopenic purpura, and thrombotic thrombocytopenic purpura. This article presents the evidence and interpretation of the blood transfusion provisions for children with hematological diseases in the "Guideline for pediatric transfusion", aiming to assist in the understanding and implementing the blood transfusion section of this guideline.
Humans ; Child ; Hematologic Diseases/therapy* ; Blood Transfusion/standards* ; Practice Guidelines as Topic

To guide clinical blood transfusion practices for pediatric patients, the National Health Commission has issued the health standard "Guideline for pediatric transfusion" (WS/T 795-2022). Blood transfusion for children undergoing hematopoietic stem cell transplantation is highly complex and challenging. This guideline provides recommendations on transfusion thresholds and the selection of blood components for these children. This article presents the evidence and interpretation of the transfusion provisions for children undergoing hematopoietic stem cell transplantation, with the aim of enhancing the understanding and implementation of the "Guideline for pediatric transfusion".
Humans ; Hematopoietic Stem Cell Transplantation ; Child ; Blood Transfusion/standards* ; Practice Guidelines as Topic

To guide clinical blood transfusion practices for pediatric patients, the National Health Commission has issued the health standard "Guideline for pediatric transfusion" (WS/T 795-2022). Critically ill children often present with anemia and have a higher demand for transfusions compared to other pediatric patients. This guideline provides guidance and recommendations for blood transfusions in cases of general critical illness, septic shock, acute brain injury, extracorporeal membrane oxygenation, non-life-threatening bleeding, and hemorrhagic shock. This article interprets the background and evidence of the blood transfusion provisions for critically ill and severely bleeding children in the "Guideline for pediatric transfusion", aiming to enhance understanding and implementation of this aspect of the guidelines. Citation:Chinese Journal of Contemporary Pediatrics, 2025, 27(4): 395-403.
Humans ; Critical Illness ; Blood Transfusion/standards* ; Child ; Hemorrhage/therapy* ; Practice Guidelines as Topic

To guide clinical blood transfusion practices in pediatric patients, the National Health Commission has issued the health standard "Guideline for pediatric transfusion" (WS/T 795-2022). Children undergoing cardiac surgery are at high risk of bleeding, and the causes of perioperative anemia and coagulation disorders in neonates and children are complex and varied, often necessitating the transfusion of allogeneic blood components. This guideline provides direction and recommendations for specific measures in blood management for children undergoing cardiac surgery before, during, and after surgery. This article interprets the background and evidence for the formulation of the blood transfusion provisions for children undergoing cardiac surgery, hoping to facilitate the understanding and implementation of this guideline.
Humans ; Cardiac Surgical Procedures ; Blood Transfusion/standards* ; Child ; Practice Guidelines as Topic