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.

Objective:To explore the mediating chain effect between attachment and coping style of disease perception and hope in patients with advanced lung cancer, and to provide theoretical basis for improving coping style in patients with advanced lung cancer.Methods:From October 2021 to June 2022, 354 patients with advanced lung cancer in the First and Second Affiliated Hospitals of Anhui Medical University were selected by convenience sampling. The general information questionnaire, the Experiences in Close Relationships Inventory, the Brief Illness Perception Questionnaire, the Herth Hope Index, and the Medical Coping Modes Questionnaire were used to conduct cross-sectional questionnaire survey. SPSS 25.0 software and Bootstrap method were used to construct and verify the chain mediation model.Results:Finally, 336 patients with advanced lung cancer were included, including 214 males and 122 females, aged 27-79(59.43 ± 8.61) years old. Attachment avoidance score was (3.31 ± 1.01) points, attachment anxiety score was (3.86 ± 1.17) points, illness perception score was (40.07 ± 12.01) points, hope score was (34.05 ± 5.87) points, and face coping score was (18.75 ± 5.34) points in patients with advanced lung cancer. The avoidance coping score was (15.47 ± 1.97) points, and the yielding coping score was (9.62 ± 3.85) points. In patients with advanced lung cancer, attachment avoidance and attachment anxiety were positively correlated with yield coping ( r=0.448, 0.747, both P<0.01), positively correlated with illness perception ( r=0.356, 0.627, both P<0.01), and negatively correlated with hope ( r=-0.406, -0.670, both P<0.01). Illness perception was positively correlated with yield coping ( r=0.744, P<0.01), and negatively correlated with hope ( r=-0.628, P<0.01). Hope was negatively correlated with yield response ( r=-0.769, P<0.01). The mediation model showed that the chain mediating effect of attachment avoidance, illness perception, hope and yield coping was significant in patients with advanced lung cancer, with an effect value of 0.009 and an effect size of 13.95%. The chain mediating effect of attachment anxiety, illness perception, hope and yield coping were significant, with an effect value of 0.010 and an effect size of 8.27%. Conclusions:Attachment can not only directly predict submission coping in advanced lung cancer patients, but also indirectly predict submission coping through the chain mediation of illness perception and hope.

Objective To observe the value of apparent diffusion coefficient(ADC)for evaluating short-term efficacy of TACE for treating colorectal cancer liver metastases(CRLM).Methods Data of 60 liver metastases in 28 CRLM patients who underwent TACE were retrospectively analyzed.Based on MRI after the first TACE,according to the response evaluation criteria of solid tumors,the liver metastases were divided into response group(n=38)and non-response group(n=22).ADC parameters obtained with diffusion weighted imaging(DWI)before and after TACE,including ADC before TACE(ADCpre),after the first TACE(ADCpost1)and after the second TACE(ADCpost2)were compared between groups,while ADC change value(ΔADC)and the percentage of ΔADC were calculated.The maximum diameter of the target foci were measured,and the correlation between ΔADCpost1 and the change of the maximum diameter of target foci were analyzed.Receiver operating characteristic curve was drawn,the area under the curve(AUC)was calculated to observe the efficacy of ΔADCpost1 for evaluating short-term efficacy of TACE for CRLM.Results No significant difference of ADCpre was found between groups(P=0.484).After the first TACE,ADCpost1,ΔADCpost1 and percentage of ΔADCpost1 in response group were all higher than those in non-response group(all P＜0.05).After the second TACE,no significant difference of ADCpost2,ΔADCpost2 nor percentage of ΔADCpost2 was found between groups(all P＞0.05).The maximum diameter change of the target foci after the first TACE was(-0.48±0.93)cm,which was negatively correlated with ΔADCpost1(rs=-0.347,P=0.007).AUC of ΔADCpost1 for evaluating short-term efficacy of TACE for CRLM was 0.717.Conclusion ADC had good efficacy for evaluating short-term efficacy of TACE for treating CRLM.

In recent years, nucleic acid therapy, as a revolutionary therapeutic tool, has shown great potential in the treatment of genetic diseases, infectious diseases and cancer. Lipid nanoparticles (LNPs) are currently the most advanced mRNA delivery carriers, and their emergence is an important reason for the rapid approval and use of COVID-19 mRNA vaccines and the development of mRNA therapy. Currently, mRNA therapeutics using LNP as a carrier have been widely used in protein replacement therapy, vaccines and gene editing. Conventional LNP is composed of four components: ionizable lipids, phospholipids, cholesterol, and polyethylene glycol (PEG) lipids, which can effectively load mRNA to improve the stability of mRNA and promote the delivery of mRNA to the cytoplasm. However, in the face of the complexity and diversity of clinical diseases, the structure, properties and functions of existing LNPs are too homogeneous, and the lack of targeted delivery capability may result in the risk of off-targeting. LNPs are flexibly designed and structurally stable vectors, and the adjustment of the types or proportions of their components can give them additional functions without affecting the ability of LNPs to deliver mRNAs. For example, by replacing and optimizing the basic components of LNP, introducing a fifth component, and modifying its surface, LNP can be made to have more precise targeting ability to reduce the side effects caused by treatment, or be given additional functions to synergistically enhance the efficacy of mRNA therapy to respond to the clinical demand for nucleic acid therapy. It is also possible to further improve the efficiency of LNP delivery of mRNA through machine learning-assisted LNP iteration. This review can provide a reference method for the rational design of engineered lipid nanoparticles delivering mRNA to treat diseases.

Background::Although overnight fasting is recommended prior to endoscopic retrograde cholangiopancreatography (ERCP), the benefits and safety of high-carbohydrate fluid diet (CFD) intake 2 h before ERCP remain unclear. This study aimed to analyze whether high-CFD intake 2 h before ERCP can be safe and accelerate patients’ recovery.Methods::This prospective, multicenter, randomized controlled trial involved 15 tertiary ERCP centers. A total of 1330 patients were randomized into CFD group ( n = 665) and fasting group ( n = 665). The CFD group received 400 mL of maltodextrin orally 2 h before ERCP, while the control group abstained from food/water overnight (>6 h) before ERCP. All ERCP procedures were performed using deep sedation with intravenous propofol. The investigators were blinded but not the patients. The primary outcomes included postoperative fatigue and abdominal pain score, and the secondary outcomes included complications and changes in metabolic indicators. The outcomes were analyzed according to a modified intention-to-treat principle. Results::The post-ERCP fatigue scores were significantly lower at 4 h (4.1 ± 2.6 vs. 4.8 ± 2.8, t = 4.23, P <0.001) and 20 h (2.4 ± 2.1 vs. 3.4 ± 2.4, t= 7.94, P <0.001) in the CFD group, with least-squares mean differences of 0.48 (95% confidence interval [CI]: 0.26–0.71, P <0.001) and 0.76 (95% CI: 0.57–0.95, P <0.001), respectively. The 4-h pain scores (2.1 ± 1.7 vs. 2.2 ± 1.7, t = 2.60, P = 0.009, with a least-squares mean difference of 0.21 [95% CI: 0.05–0.37]) and positive urine ketone levels (7.7% [39/509] vs. 15.4% [82/533], χ2 = 15.13, P <0.001) were lower in the CFD group. The CFD group had significantly less cholangitis (2.1% [13/634] vs. 4.0% [26/658], χ2 = 3.99, P = 0.046) but not pancreatitis (5.5% [35/634] vs. 6.5% [43/658], χ2 = 0.59, P = 0.444). Subgroup analysis revealed that CFD reduced the incidence of complications in patients with native papilla (odds ratio [OR]: 0.61, 95% CI: 0.39–0.95, P = 0.028) in the multivariable models. Conclusion::Ingesting 400 mL of CFD 2 h before ERCP is safe, with a reduction in post-ERCP fatigue, abdominal pain, and cholangitis during recovery.Trail Registration::ClinicalTrials.gov, No. NCT03075280.

Objective To investigate the risk factors for bronchopulmonary dysplasia (BPD) in preterm infants,and to establish a risk prediction model. Methods A total of 120 preterm infants who were admitted to the neonatal intensive care unit of Shanghai Children's Hospital from January to December 2022 were included. According to the diagnostic criteria for BPD released by the National Institute of Child Health and Human Development in 2018,they were divided into a non-BPD group (84 infants) and a BPD group (36 infants). The clinical data of the infants and their mothers were compared between the two groups. The univariate analysis and the stepwise multivariate regression analysis were used to identify the risk factors for BPD and establish a risk prediction model. Results The results showed that a gestational age of<28 weeks,duration of noninvasive respiratory support,comorbidity with infectious pneumonia,and chorioamnionitis in the mother were independent risk factors for BPD in preterm infants (P<0.05). A nomogram model for predicting the development of BPD was established based on the risk factors,with an area under the receiver operating characteristic curve of 0.93,and the calibration curve of this nomogram had a slope of about 1. The goodness-of-fit test indicated the model fitted well (x2=8.287,P=0.406). Conclusions A gestational age of<28 weeks,duration of noninvasive respiratory support,comorbidity with infectious pneumonia,and chorioamnionitis in the mother are independent risk factors for BPD in preterm infants.

Objective To compare clinical effect between open reduction and fixation with cannulated screw and threaded rivet via posteromedial approach versus arthroscopic Endobutton plate fixation in treating posterior cruciate ligament avulsion fractures.Methods Clinical data of 38 patients with posterior cruciate ligament avulsion fractures from July 2020 to December 2021 were analyzed retrospectively,and divided into open reduction and internal fixation group(posterior medial approach hollow anchor system fixation)and arthroscopic fixation group(Endobutton with loop plate fixation under arthroscopy).There were 20 patients in open reduction and internal fixation group,including 16 males and 4 females,aged from 26 to 74 years old with an average of(42.9±18.8)years old;13 patients on the left side and 7 patients on the right side;12 patients were classi-fied to type Ⅱ and 8 patiens with type Ⅲ according to Meyers-McKeever fractures classification;14 patients were grade Ⅱ and 6 patients were grade Ⅲ in back drawer test.There were 18 patients in arthroscopic fixation group,including 11 males and 7 fe-males;aged from 24 to 70 years old with an average of(53.5±13.4)years old;11 patients on the left side and 7 patients on the right side;10 patients were classified to type Ⅱ and 8 patiens with type Ⅲ according to Meyers-McKeever fractures classifica-tion;11 patients were grade Ⅱ and 7 patients were grade Ⅲ in back drawer test.Operation time,blood loss,and quality of im-mediate reduction were compared between two groups.Knee range of motion,knee back drawer test,and International Knee Documentation Committee(IKDC)grading,KT2000 stability evaluation and Lysholm function score of knee joint were com-pared at 6 months after operation.Results All patients were followed up for 8 to 16 months with an average of(12.3±1.9)months.There were no complications such as incision infection,fracture malunion or non-union,and internal fixation loosening occurred.The avulsion fractures of knee joint were reached to imaging healing standard at 6 months after operation.Operation time and blood loss in open reduction and internal fixation group were(56.4±7.1)min and(63.2±10.2)ml,while(89.9±7.4)min and(27.7±8.7)ml in arthroscopic fixation group,respectively,and had significant difference between two groups(P＜0.05).There were no differences in immediate reduction quality(x2=0.257,P=0.612),knee joint range of motion at 6 months after opertaion(t=0.492,P=0.626),knee joint rear drawer test(x2=0.320,P=0.572),IKDC classification of knee joint(x2=0.127,P=0.938),KT2000stability evaluation(x2=0.070,P=0.791),and knee Lysholmfunction score(t=0.092,P=0.282)between two groups.Conclusion Posterior medial approach with hollow anchoring system fixation and arthroscopic Endobutton with loop plate fixa-tion for the treatment of posterior cruciate ligament tibial occlusion avulsion fracture could achieve satisfactory clinical results,and arthroscopic surgery has less bleeding,but also has a longer learning curve and longer operation time than traditional inci-sion surgery.The surgeon needs to make a choice according to clinical situation of patient and their own surgical inclination.

Objective:To translate the Dysfunctional Beliefs and Attitudes about Sleep Scale for Cancer Patients (C-DBAS-14) into Chinese and test its reliability and validity.Methods:The Korean version of C-DBAS-14 was translated, back-translated, and culturally adapted into Chinese based on Brislin's translation model, forming the Chinese version of C-DBAS-14. From October 2022 to May 2023, 361 hospitalized cancer patients at the First Affiliated Hospital of Anhui Medical University were selected as research objects by convenient sampling method. They were surveyed using a general information questionnaire, the Chinese version of C-DBAS-14, the Insomnia Severity Index (ISI), and the Hospital Anxiety and Depression Scale (HADS) to evaluate the reliability and validity of the scale. The scale's item analysis was based on correlation coefficients and critical ratio values; structural validity, content validity, and convergent validity were used to evaluate the scale's validity; Cronbach's α coefficient and intraclass correlation coefficient were used to assess its reliability.Results:A total of 361 questionnaires were distributed, 356 were effectively returned, with an effective response rate of 98.6% (356/361). The Chinese version of C-DBAS-14 contained 14 items across four dimensions. The scale-level content validity index was 0.976, and the item-level content validity index ranged from 0.833 to 1.000. Totally four common factors were extracted in exploratory factor analysis, explaining 78.8% of the total variance. Confirmatory factor analysis showed a Chi-square/degrees of freedom ratio of 1.286, comparative fit index of 0.991, goodness of fit index of 0.945, incremental fit index of 0.991, Tucker-Lewis index of 0.988, and root mean square error of approximation of 0.036. The total Cronbach's α coefficient of the scale was 0.874, and the intraclass correlation coefficient was 0.863. The C-DBAS-14 score was negatively correlated with the ISI and HADS scores ( r=-0.734, -0.639; P<0.01) . Conclusions:The Chinese version of C-DBAS-14 has good reliability and validity and can be used as an assessment tool for irrational sleep beliefs in Chinese cancer patients.

The epidemiology and etiology of three suspected cases of imported skin diphtheria infection in Fujian Province were investigated.Secretion samples of patients with skin damage were collected for isolation and culture of Corynebacterium diphtheriae.Biochemical identification and mass spectrum analysis of pure cultures of suspected C.diphtheriae were conduc-ted,the virulence-related genes,including diphtheria toxin reporter(dtxR),toxin A(toxA),and toxin B(toxB)were detec-ted,and multilocus sequence typing(MLST)was performed.All three cases had typical clinical manifestations of cutaneous diphtheria,and C.diphtheriae was isolated from the damaged skin.The virulence genes of two C.diphtheriae strains isolated from two cases were identified as dtxR(+),toxA(-),and toxB(-),and the MLST type was ST-703.The virulence genes of C.diphtheriae isolated from one case were identified as dtxR(+),toxA(+),toxB(+),and the MLST type was ST-248.There is an increased risk of diphtheria in Fujian Province.C.diphtheriae without diphtheria toxin genes can also cause skin diphtheria.

Objective:To screen interleukin(IL)-1β secretion-related membrane transporters by macrophage experiment in vitro and conventional knockout mice.Methods:THP-1 cell line was differentiated to obtain human THP-1-derived macrophages,and the primary macrophages were obtained from human peripheral blood.FVB wild-type mice with the same sex and age were used as the controls of MRP1 knockout mice.The macrophages in abdominal cavity and bone marrow of mice were cultivated.The cells were treated with ABCC1/MRP1,ABCG2/BCRP,ABCB1/P-gp,OATP1B1,and MATE transporter inhibitors,then stimulated by lipopolysaccharide and adenosine triphosphate.The secretion level of IL-iβ was detected by ELISA,Western blot,and immunofluorescence.Results:After inhibiting ABCC1/MRP1 transporter,the secretion of IL-1β decreased significantly,while inhibition of the other 4 transporters had no effect.In animal experiment,the level of IL-1 β secreted by macrophages in bone marrow of MRP1 knockout mice was significantly lower than control group(P＜0.05).Conclusion:ABCC1/MRP1 transporter is a newly discovered IL-1β secretion pathway,which is expected to become a new target for solving clinical problems such as cytokine release syndrome.