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.

ObjectiveTo analyze the changes in the degree of coordination of China's major epidemic prevention and control efforts before and after the outbreak of the Corona Virus Disease 2019 (COVID-19), so as to explore the impact of epidemic prevention and control measures on coordination dynamics. MethodsA total of 3 864 policy documents related to epidemic prevention and control from January 2000 to December 2020 across 31 provinces (autonomous regions, and municipalities) in China were systematically collected. Contents specific to collaborative and cooperative efforts were extracted, and the extent of interdepartmental coordination were quantified to assess the effectiveness of epidemic prevention and control efforts. Wilcoxon signed-rank test was adopted to statistically analyze the differences between the indicators before and after the epidemic. ResultsThe average overall coordination level for major epidemic prevention and control in 31 provinces (autonomous regions, and municipalities) increased from 43.06% to 97.62%, and the average coordination levels in the eastern, central, and western China soared from 42.29%, 37.50%, and 47.46%, to 98.81%, 96.20%, and 97.46%, respectively, with statistically significant differences (all P<0.05). In terms of department categorization, coordination levels in the professional departments and the key support departments peaked at 100.00%, while other support departments rose to 95.43%, with an increase of 77.15%, 181.85%, and 139.89%, respectively, exhibiting noteworthy statistically significant differences (all P<0.001). ConclusionThe scope of coordination departments of China’s major epidemic prevention and control exists a remarkable surge following the COVID-19 outbreak, notable heightened coordination is particularly observed among the key support departments. Future endeavors should prioritize the roles played by diverse departments in epidemic prevention and control, enhancing both the clarity of departmental responsibilities and the effectiveness of interdepartmental coordination.

ObjectiveTo systematically evaluate the public health governance capacity of 40 cities in Jiangsu, Zhejiang, and Anhui Provinces, providing a scientific evaluation basis for building a "Healthy Yangtze River Delta". MethodsA comprehensive collection of policy documents, public information reports, and research literature related to public health governance capacity in Jiangsu, Zhejiang, and Anhui Provinces was conducted, totaling 6 920 policy documents, 1 720 information reports, and 1 200 literature pieces. Based on the evaluation standards for an appropriate public health system established by the research team, the basic status of public health governance capacity was assessed to identify the strengths and weaknesses of the 40 cities. ResultsIn 2022, the public health governance capacity score for the 40 cities in Jiangsu, Zhejiang, and Anhui Provinces was (562.5±38.0) points. In terms of specific areas, the emergency response field received the highest score of (791.4±49.7) points, while the chronic disease prevention and control field received the lowest score of (368.2±29.6) points. The Jiangsu-Zhejiang-Anhui region has largely achieved the strategic priority of health, gradually improved public health legal regulations, and established a basic organizational framework with a solid foundation for information and data infrastructure. However, challenges still need to be addressed, such as unstable government funding for public health, unclear departmental responsibilities, and barriers to information interoperability. ConclusionThe public health governance capacity of the 40 cities in Jiangsu, Zhejiang, and Anhui Province has been at a moderate level, but disparities have still existed across regions and fields. In the future, while continuing to deepen existing advantages, it is essential to accurately identify the causes of problems, establish a long-term and stable investment mechanism, enhance information connectivity mechanisms, further clarify departmental responsibilities, and promote the achievement of the "Healthy Yangtze River Delta" goal.

The analysis of ammonia nitrogen in real water samples is challenging due to matrix interferences and difficulties for rapid on-site analysis.On the basis of the standard method,i.e.water quality-determination of ammonia nitrogen-salicylic acid spectrophotometry(HJ 536-2009),a simple device for online detecting ammonia nitrogen was developed using a sequential injection analysis(SIA)system in this work.The ammonia nitrogen transformation system,color reaction system,and detection system were built in compatible with the SIA system,respectively.In particular,the detection system was assembled by employing light-emitting diode as the light source,photodiode as the detector,and polyvinylchloride tube as the cuvette,thus significantly reducing the volume,energy consumption and fabricating cost of the detection system.As a result,the accurate analysis of ammonia nitrogen in complex water samples was achieved.A quantitative detection of ammonia nitrogen in water sample was obtained in 12 min,along with linear range extending to 1000 μmol/L,precisions(Relative standard deviation,RSD)of 4.3%(C=10 μmol/L,n=7)and 4.2%(C=500 μmol/L,n=7),and limit of detection(LOD)of 0.65 μmol/L(S/N=3,n=7).The results of interfering experiments showed that the detection of ammonia nitrogen by the developed device was not interfered by the common coexisting ions and components,therefore the environmental water could be directly analyzed,such as reservoir water,domestic sewage,sea water and leachate of waste landfill.The analytical results were consistent with those obtained by the environmental protection standard method(Water quality determination of ammonia nitrogen-salicylic acid spectrophotometry,HJ 536-2009).In addition,the spiking recoveries were in the range of 92.3%-98.1%,further confirming the accuracy and practicality of the developed device.

Objective:To evaluate the association between preoperative serum β 2-microglobulin (β 2MG) concentrations and postoperative delirium (POD) in elderly patients. Methods:The study selected patients who underwent knee or hip arthroplasty under spinal-epidural anesthesia on an elective basis at Qingdao Municipal Hospital from May 2021 to November 2022. The patients were divided into a POD group and a non-POD group based on the occurrence of POD. The study was conducted as part of the Perioperative Neurocognitive Impairment and Biomarkers Lifestyle Cohort, which was a nested case-control study. The study collected baseline data from two groups of patients and analyzed the differences between them. Logistic regression was used to identify the risk factors for POD. The stability of the regression model was tested using sensitivity analysis. The mediation model was used to examine whether cerebrospinal fluid (CSF) biomarkers mediated the relationship between β 2MG and POD. The receiver operating characteristic curve was drawn and the area under the curve was calculated to evaluate the accuracy of preoperative β 2MG concentrations and CSF biomarker concentration in predicting POD. Results:There were 57 cases in POD group and 449 cases in non-POD group. The results of logistic regression analysis showed that the increased β 2MG and CSF total tau protein (t-tau) concentrations were risk factors for POD, and the increased CSF β-amyloid 42 concentration was a protective factor for POD after adjustment for multiple confounders such as age, gender, education, Mini-Mental State Examination, history of hypertension and infusion volume ( P<0.05). The results of mediation analysis showed that the serum β 2MG′s effect on POD was partly mediated by t-tau (18.1%). The results of the receiver operating characteristic curve showed that the area under the curve of the β 2MG concentration combined with the CSF biomarker concentration was 0.742. Conclusions:Elevated preoperative serum β 2MG concentration is a risk factor for POD in elderly patients, and the relationship may be partly mediated by CSF t-tau.

Objective:To evaluate the relationship between preoperative serum bilirubin concentrations and postoperative delirium (POD) in the patients undergoing knee or hip replacement.Methods:Medical records from 413 patients undergoing knee or hip arthroplasty were selected from August 2020 to October 2023 at Qingdao Municipal Hospital using a nested case-control design based on the PNDABLE study cohort. The patients were divided into POD group ( n=77) and non-POD group ( n=336) according to whether POD occurred. Univariate analysis was used to analyze the influencing factors. Logistic regression was used to identify the risk factors for POD. The significance of mediation effect was tested. The receiver operating characteristic curve was drawn to evaluate the accuracy of risk factors in predicting POD. Results:There were significant differences in age, education time, ratio of diabetes history, Memorial Delirium Assessment Scale score, total bilirubin concentration, direct bilirubin concentration, indirect bilirubin concentration, Aβ 42 concentration, p-tau concentration, t-tau concentration, Aβ 42/p-tau ratio and Aβ 42/t-tau ratio between POD group and non-POD group ( P<0.05). The results of logistic regression analysis showed that preoperative serum total bilirubin, direct bilirubin and indirect bilirubin were risk factors for POD ( P<0.05). The results of mediation effects showed that the concentration of total tau protein in CSF partly mediated the relationship between high serum total bilirubin, direct bilirubin and indirect bilirubin concentrations and POD. The area under the receiver operating characteristic curve of total bilirubin, direct bilirubin and indirect bilirubin combined with CSF biomarker concentrations in predicting POD was 0.83 ( P<0.001). Conclusions:Preoperative elevated concentrations of total bilirubin, direct bilirubin and indirect bilirubin are risk factors for POD in the patients undergoing knee or hip replacement. CSF t-tau concentration has a partly mediating role in the association between serum total bilirubin, direct bilirubin and indirect bilirubin concentrations and the development of POD.

Based on the genomic information of Emericella sp. 1454, in conjunction with literature analysis of its secondary metabolite emestrin, this study identified the biosynthetic precursors of emestrin and enhanced its production by supplementing the culture medium with these precursors. In this study, it was found for the first time that the addition of biosynthetic precursor, reduced glutathione, to the culture medium significantly increased emestrin yield. By incorporating 1.5 g of reduced glutathione into 50 g of rice culture medium and fermenting for 15 days, a yield of 30.82 mg of emestrin was obtained, which marked an 11.71-fold increase compared to the original fermentation approach. The method is both simple and cost-effective, establishing a solid foundation for the efficient synthesis of emestrin and similar compounds. Additionally, it serves as an important reference for enhancing the production of other epipolythiodioxopiperazine compounds.

Objective To explore the possible therapeutic mechanism of Gastrodin Injection combined with ganglioside in the adjuvant treatment of spinal cord injury(SCI)based on NOD-like receptor thermal protein domain associated protein 3(NLRP3)signaling pathway.Methods A total of 108 patients with SCI were randomly divided into an observation group and a control group,with 54 cases in each group.Both groups were given routine rehabilitation training.Additionally,the control group was treated with intravenous drip of ganglioside,and the observation group was treated with intravenous drip of Gastrodin Injection combined with ganglioside.A course of treatment covered 30 days and the two groups were treated for 2 continuous courses.The time for the recovery of muscle strength,time to leave a sickbed for walking and time to stay in hospital for observation were compared between the two groups.The American Spinal Injury Association(ASIA)score and the serum levels of brain-derived neurotrophic factor(BDNF),central nervous specific protein(S-100β),interleukin(IL)-1β,IL-18,NLRP3,cystein-containing aspartate specific protease 1(Caspase-1)and apoptosis-associated speck-like protein containing a CARD(ASC)in the two groups were observed before and after treatment.After treatment,the clinical efficacy and safety of the two groups were evaluated.Results(1)After two courses of treatment,the total effective rate of the observation group was 83.33%(45/54),and that of the control group was 66.67%(36/54).The intergroup comparison(tested by chi-square test)showed that the curative effect of the observation group was significantly superior to that of the control group(P＜0.05).(2)After treatment,the time for the recovery of muscle strength,time to leave a sickbed for walking and time to stay in hospital for observation in the observation group were significantly shorter than those in the control group(P＜0.01).(3)After one and 2 courses of treatment,the ASIA scores of pain sense,motor sense and tactile sensation in the two groups were significantly higher than those before treatment(P＜0.05),and the scores after 2 courses of treatment were higher than those after one course of treatment(P＜0.05).The intergroup comparison showed that the increase of ASIA scores of pain sense,motor sense and tactile sensation in the observation group after one and 2 courses of treatment was significantly superior to that in the control group(P＜0.05).(4)After one and 2 courses of treatment,the serum BDNF level in the two groups was higher than that before treatment(P＜0.05)and the levels of NLRP3,ACS,Caspase-1 protein and serum IL-1β,IL-18 and S-100β were lower than those before treatment(P＜0.05),and the changes in the levels of above indicators in the two groups after 2 courses of treatment were more obvious than those after one course of treatment(P＜0.05).The intergroup comparison showed that the increase of serum BDNF level and the decrease of the levels of protein NLRP3,ACS,Caspase-1 and serum IL-1β,IL-18 and S-100β in the observation group were significantly superior to those in the control group(P＜0.05).(5)During the treatment,no drug-related adverse reactions occurred in the two groups.Conclusion Gastrodin Injection combined with ganglioside exerts certain effect for the treatment of SCI patients.The combined therapy is effective on relieving the neuroinflammatory response and promoting the recovery of neurological function by regulating the NLRP3 inflammasomes,and its curative effect is superior to that of ganglioside alone.

The core of theory of visceral manifestation of spleen is about'spleen in charge of transportation and transformation,spleen qi dispersing the essence'.Middle-jiao spleen-earth has the functions of digesting food and transporting food essence,and maintaining the homeostasis of glucose and lipid metabolism in the body.'Spleen in charge of transportation and transformation,spleen qi dispersing the essence'functions like the glucose and lipid metabolism at physiological state.The deficiency of spleen results in the dysfunction of food in-take and digestion and the susceptibility to external pathogens;qi deficiency and blood stasis lead to the interior damp-heat,and the long-term accumulation of damp-heat develops into stasis and then turns into toxins,which eventually induces inflammation-to-tumor transition.The pathogenesis of'spleen deficiency being the root cause and stasis blended with toxins'is correlated with the pathological changes of inflammation-to-tumor transition.The therapy of strengthening the spleen,dispersing essence and removing turbidity is effective on improving the disorder of glucose and lipid metabolism,and the therapy of strengthening the spleen,resolving stasis and removing toxin is effective on restraining the process of inflammation-to-tumor transition in the stomach.It has become a new direction in the field of spleen-stomach research to expound the scientific connotation of the essence of spleen function of'spleen in charge of transportation and transformation,spleen qi dispersing the essence'from the perspective of glucose and lipid metabolism,to focus on the inflammation-to-tumor transition process of major diseases of digestive system,to explore the evolution of the traditional Chinese medicine syndromes of inflammatory diseases and precancerous lesions of the digestive tract,and to reveal the pharmacological mechanism of treatment from the perspective of spleen,which will enrich the scientific connotation of theory of visceral manifestation of spleen and promote the modernization and internationalization of traditional Chinese medicine.

Objective To investigate the distribution of traditional Chinese medicine(TCM)syndromes and related risk factors in children with mycoplasma pneumoniae pneumonia(MPP).Methods The clinical data of 420 children with MPP admitted to the First Affiliated Hospital of Guangzhou University of Chinese Medicine were collected.The clinical data included gender,age,history of respiratory tract diseases,TCM syndromes,MPP classification,cough duration,fever duration,fever peak value,laboratory indicators of C-reactive protein(CRP),procalcitonin(PCT)and lactate dehydrogenase(LDH),and the complication of infection.SPSS 26.0 software was used for data statistics,and then the distribution of TCM syndromes in children with MPP and its correlation with various clinical data,as well as the related risk factors of MPP with different classification and various TCM syndromes were explored.Results(1)Among the 420 children with MPP,there were 283 cases(67.4％)of mild MPP,76 cases(18.1％)of refractory MPP,and 61 cases(14.5％)of severe MPP.For the distribution of TCM syndromes,there were 152 cases(36.2％)of wind-heat obstructing the lung syndrome,141 cases(33.6％)of phlegm-heat obstructing the lung syndrome,77 cases(18.3％)of damp-heat obstructing the lung syndrome,25 cases(6.0％)of toxin-heat obstructing the lung syndrome,16 cases(3.8％)of lung-spleen qi deficiency syndrome,and 9 cases(2.1％)of yin deficiency and lung heat syndrome.For the classification of infection,there were 295 cases(70.2％)of simple mycoplasma pneumoniae(MP)infection and 125 cases(29.8％)of mixed infection.(2)There were statistically significant differences in age stratification and visit season among MPP children with different TCM syndromes(P＜0.01),while no significant differences were shown in the gender,history of respiratory tract diseases,and the complication of infection(P＞0.05).(3)There were statistically significant differences in the visit season,history of respiratory tract diseases,and the complication of infection among the children with various MPP types(P＜0.05),while no significant differences were shown in the gender and age stratification(P＞0.05).(4)There were statistically significant differences in laboratory indicators of CRP and PCT and in the symptoms of cough duration,fever duration and fever peak among MPP children with different TCM syndromes(P＜0.05 or P＜0.01).(5)Significant differences were presented in laboratory indicators of PCT and LDH and in the symptoms of cough duration,fever duration and fever peak value among the children with different MPP types(P＜0.05 or P＜0.01).(6)Multivariate logistic regression analysis showed that CRP level ≥10.5 mg/L and wind-heat obstructing the lung syndrome were the independent risk factors for mild MPP(P＜0.05 or P＜0.01);fever duration≥7 days,cough duration ≥ 12 days and phlegm-heat obstructing the lung syndrome were the independent risk factors for refractory MPP(P＜0.05 or P＜0.01);cough duration ≥ 12 days,mixed infection and toxin-heat obstructing the lung syndrome were the independent risk factors for severe MPP(P＜0.01).Conclusion The results indicated that the classification MPP in children is predominated by mild MPP,and their TCM syndrome types is predominated by wind-heat obstructing the lung syndrome.The proportions of refractory MPP and damp-heat obstructing the lung syndrome increase significantly in autumn,which may be related to the characteristics of regional environment and circuit qi.The increase of CRP level and fever peak may be related to phlegm-heat obstructing the lung syndrome and toxin-heat obstructing the lung syndrome.In clinic,attention should be paid to the early use of heat-clearing and phlegm-resolving drugs or heat-clearing and toxin-removing drugs;children with the history of respiratory tract diseases and mixed infections are more likely to develop into severe MPP,and the physicians should be alert clinically.Wind-heat obstructing the lung syndrome,phlegm-heat obstructing the lung syndrome and toxin-heat obstructing the lung syndrome are the independent risk factor separately for mild MPP,refractory MPP and severe MPP,which requires timely intervention to prevent mild MPP from developing into refractory MPP or severe MPP in clinic.