To analyze the epidemiological characteristics of COVID-19 in Fujian Province from the 49th week of 2022 to the 5th week of 2023,after further optimization of China's COVID-19 prevention and control measures on December 7,2022(the 49th week of 2022),this study used multi-dimensional surveillance data to dynamically assess population infection levels and their changing trends.The aim of the study was to provide a scientific basis for early warning of epidemic risk,medical resource allocation,and evalu-ation of socio-economic impact.A multi-source data surveillance system was constructed,encompassing surveillance of fever clinics at medical institutions(weekly collection of visits,positive nucleic acid and antigen test results,inpatients,and severe cases in sec-ondary or above hospitals),population nucleic acid test monitoring(weekly person-times and positivity rates of single-tube tests from the provincial system),sentinel hospital monitoring(weekly proportion of influenza-like illness visits at 18 sentinel hospitals and re-lated viral testing data),and monitoring of novel coronavirus variants(weekly systematic collection of genomic sequences of local and imported cases).Line charts were plotted weekly,and time series analysis,molecular epidemiological methods,and an improved SEIAR model were used to simulate epidemic spread.During the study period,the COVID-19 epidemic in Fujian Province exhibited three distinct stages.In the infection peak stage(52nd week of 2022),the provincial fever clinic visits reached 606 893 person-times,and a 49.2%positivity rate in population single-tube nucleic acid tests and 63.8%positivity rate in sentinel hospital monitoring were observed.In the medical load peak stage(2nd week of 2023),274 460 inpatients and 28 487 severe cases were recorded.In the epidemic decline stage(4th to 5th weeks of 2023),fever clinic visits decreased by 96.3%with respect to the peak,the single-tube nucleic acid test positivity rate decreased to 6.3%,and the sentinel hospital COVID-19 nucleic acid test positivity rate was 6.4%.All 508 sequenced local cases were Omicron variants,predominantly BA.5.2 and its sub-lineages(67.4%).Among 56 imported se-quenced cases,BA.5.2 and its sub-lineages accounted for 50.0%,and 16.1%comprised nine variants of interest including XBB and BQ.The model predicted the infection peak in the 52nd week of 2022,whereas the hospitalization peak lagged by approximately 10.6 days.Multi-source data monitoring revealed a three-stage development of the COVID-19 epidemic in Fujian.The BA.5.2 strain was dominant during the epidemic.The combination of multi-source monitoring data and modeling provides important references for epi-demic prevention and control,and highlights the need to improve the monitoring system in follow-up.

To analyze the epidemiological characteristics of COVID-19 in Fujian Province from the 49th week of 2022 to the 5th week of 2023,after further optimization of China's COVID-19 prevention and control measures on December 7,2022(the 49th week of 2022),this study used multi-dimensional surveillance data to dynamically assess population infection levels and their changing trends.The aim of the study was to provide a scientific basis for early warning of epidemic risk,medical resource allocation,and evalu-ation of socio-economic impact.A multi-source data surveillance system was constructed,encompassing surveillance of fever clinics at medical institutions(weekly collection of visits,positive nucleic acid and antigen test results,inpatients,and severe cases in sec-ondary or above hospitals),population nucleic acid test monitoring(weekly person-times and positivity rates of single-tube tests from the provincial system),sentinel hospital monitoring(weekly proportion of influenza-like illness visits at 18 sentinel hospitals and re-lated viral testing data),and monitoring of novel coronavirus variants(weekly systematic collection of genomic sequences of local and imported cases).Line charts were plotted weekly,and time series analysis,molecular epidemiological methods,and an improved SEIAR model were used to simulate epidemic spread.During the study period,the COVID-19 epidemic in Fujian Province exhibited three distinct stages.In the infection peak stage(52nd week of 2022),the provincial fever clinic visits reached 606 893 person-times,and a 49.2%positivity rate in population single-tube nucleic acid tests and 63.8%positivity rate in sentinel hospital monitoring were observed.In the medical load peak stage(2nd week of 2023),274 460 inpatients and 28 487 severe cases were recorded.In the epidemic decline stage(4th to 5th weeks of 2023),fever clinic visits decreased by 96.3%with respect to the peak,the single-tube nucleic acid test positivity rate decreased to 6.3%,and the sentinel hospital COVID-19 nucleic acid test positivity rate was 6.4%.All 508 sequenced local cases were Omicron variants,predominantly BA.5.2 and its sub-lineages(67.4%).Among 56 imported se-quenced cases,BA.5.2 and its sub-lineages accounted for 50.0%,and 16.1%comprised nine variants of interest including XBB and BQ.The model predicted the infection peak in the 52nd week of 2022,whereas the hospitalization peak lagged by approximately 10.6 days.Multi-source data monitoring revealed a three-stage development of the COVID-19 epidemic in Fujian.The BA.5.2 strain was dominant during the epidemic.The combination of multi-source monitoring data and modeling provides important references for epi-demic prevention and control,and highlights the need to improve the monitoring system in follow-up.

OBJECTIVE To establish a preparation system for megakaryocytes(MKs)derived from human embryonic stem cells(hESCs)and MK microparticles(MKMPs),and to assess the pro-angio-genic efficiency of these microparticles.METHODS ①hESCs were induced to mesodermal progenitor cells via monolayer culture with the first-stage induction medium for 2 days before the cells were induced to hemogenic endothelial/hematopoietic progenitor cells by culturing with the second-stage induction medium for another 3 days.Then,the cells were dissociated into single cells,seeded into the third-stage induction medium,and cultured using the suspension method for 8 days to obtain MKs.The specific characters of differentiated cells were identified through morphological observation and flow cytometry before stage-specific marker proteins in different periods were analyzed[hESCs:TRA-1-60,sialyl glycolipid stage-specific embryonic antigen4(SSEA4)];mesodermal progenitor cells:brachyury;hemogenic endothelial/hematopoietic progenitor cells:CD34,CD43;MKs:CD41a,CD42b),and immu-nofluorescence staining[β1-tubulin,von Willebrand factor(VWF)],[friend leukemia integration 1(FLI1),CD42].② MKMP collection and verification:MKMPs were collected via differential centrifugation.The concentration and size of these MKMPs were determined by nanoparticle tracking analysis(NTA),and both the morphology and ultrastructure were examined by transmission electron microscopy(TEM).Besides,the MKMPs-specific proteins[CD41,tumor susceptibility gene 101(TSG101)and CD9]were detected by Western blotting analysis.③ Biological function of MKMPs:MKMPs were stained with CD41a-PE antibodies and co-cultured with human umbilical veinvascular endothelial cells(HUVECs)labeled by CD34-APC for 3 h.Live-cell immunofluorescence was employed to find out whether HUVECs could absorb MKMPs.To find out whether MKMPs could affect the role of HUVECs in angio-genesis and cell migration,platelet microvesicles(PMPs)were used as positive controls.The experi-mental groups were added with different concentrations of microparticles(1,5,10 and 20 mg·L-1)while the control group was given no microparticles(0 mg·L-1).The number of nodes that formed the lumen after 5 h of incubation in Matrigel was counted,and the size of healing of the scratch area was analyzed after 6 h.To elucidate the mechanism through which MKMPs impacted angiogenesis,ELISA was used out to quantitatively detect the concentration of proteins in microparticles.RESULTS ① A three-stage differentiation cultural system was established to develop hESCs into MKs.Flow cytometry revealed progressive loss of pluripotency markers SSEA4 and TRA-1-60,while the mesodermal progenitor marker brachyury peaked at d 2.Subsequently,hemogenic endothelial/hematopoietic progenitor markers CD34 and CD43 emerged at d 5,followed by megakaryocytic markers CD41a and CD42b at d 13.Immunofluorescent images further demonstrated that MKs expressed specific proteins CD42,β1-tubulin,von VWF and FLI1 at d 13.②Microparticles were collected via differential centrifuga-tion.Transmission electron microscopy revealed that their substructure exhibited a typical double-layered membrane.Nanoparticle tracking analysis indicated that the size was(164.3±14.0)nm.The result of WB demonstrated that the microparticles expressed specific markers,including TSG101,CD9 and CD41.③ MKMPs were absorbed after being co-cultured with HUVECs for 3 h and enhanced the ability of HUVECs to form tubes and migrate.Notably,the treatment of 5 mg·L-1 MKMPs was more effective than 5 mg·L-1 PMPs treatment.The results of ELISA showed that the content of VEGF from MKMPs was higher than from PMPs,which may be the key factor in regulating endothelial biological function.CONCLUSION MKs derived from hESCs can generate functional microparticles which can promote angiogenesis.

OBJECTIVE To establish a preparation system for megakaryocytes(MKs)derived from human embryonic stem cells(hESCs)and MK microparticles(MKMPs),and to assess the pro-angio-genic efficiency of these microparticles.METHODS ①hESCs were induced to mesodermal progenitor cells via monolayer culture with the first-stage induction medium for 2 days before the cells were induced to hemogenic endothelial/hematopoietic progenitor cells by culturing with the second-stage induction medium for another 3 days.Then,the cells were dissociated into single cells,seeded into the third-stage induction medium,and cultured using the suspension method for 8 days to obtain MKs.The specific characters of differentiated cells were identified through morphological observation and flow cytometry before stage-specific marker proteins in different periods were analyzed[hESCs:TRA-1-60,sialyl glycolipid stage-specific embryonic antigen4(SSEA4)];mesodermal progenitor cells:brachyury;hemogenic endothelial/hematopoietic progenitor cells:CD34,CD43;MKs:CD41a,CD42b),and immu-nofluorescence staining[β1-tubulin,von Willebrand factor(VWF)],[friend leukemia integration 1(FLI1),CD42].② MKMP collection and verification:MKMPs were collected via differential centrifugation.The concentration and size of these MKMPs were determined by nanoparticle tracking analysis(NTA),and both the morphology and ultrastructure were examined by transmission electron microscopy(TEM).Besides,the MKMPs-specific proteins[CD41,tumor susceptibility gene 101(TSG101)and CD9]were detected by Western blotting analysis.③ Biological function of MKMPs:MKMPs were stained with CD41a-PE antibodies and co-cultured with human umbilical veinvascular endothelial cells(HUVECs)labeled by CD34-APC for 3 h.Live-cell immunofluorescence was employed to find out whether HUVECs could absorb MKMPs.To find out whether MKMPs could affect the role of HUVECs in angio-genesis and cell migration,platelet microvesicles(PMPs)were used as positive controls.The experi-mental groups were added with different concentrations of microparticles(1,5,10 and 20 mg·L-1)while the control group was given no microparticles(0 mg·L-1).The number of nodes that formed the lumen after 5 h of incubation in Matrigel was counted,and the size of healing of the scratch area was analyzed after 6 h.To elucidate the mechanism through which MKMPs impacted angiogenesis,ELISA was used out to quantitatively detect the concentration of proteins in microparticles.RESULTS ① A three-stage differentiation cultural system was established to develop hESCs into MKs.Flow cytometry revealed progressive loss of pluripotency markers SSEA4 and TRA-1-60,while the mesodermal progenitor marker brachyury peaked at d 2.Subsequently,hemogenic endothelial/hematopoietic progenitor markers CD34 and CD43 emerged at d 5,followed by megakaryocytic markers CD41a and CD42b at d 13.Immunofluorescent images further demonstrated that MKs expressed specific proteins CD42,β1-tubulin,von VWF and FLI1 at d 13.②Microparticles were collected via differential centrifuga-tion.Transmission electron microscopy revealed that their substructure exhibited a typical double-layered membrane.Nanoparticle tracking analysis indicated that the size was(164.3±14.0)nm.The result of WB demonstrated that the microparticles expressed specific markers,including TSG101,CD9 and CD41.③ MKMPs were absorbed after being co-cultured with HUVECs for 3 h and enhanced the ability of HUVECs to form tubes and migrate.Notably,the treatment of 5 mg·L-1 MKMPs was more effective than 5 mg·L-1 PMPs treatment.The results of ELISA showed that the content of VEGF from MKMPs was higher than from PMPs,which may be the key factor in regulating endothelial biological function.CONCLUSION MKs derived from hESCs can generate functional microparticles which can promote angiogenesis.

Objective To identify the key factors affecting the risk of medical surges and their coupling relation5 ships,providing strategic support for medical institutions to optimize risk management and emergency governance.Methods 17 influencing factors were determined based on WSR theory,and an expert scoring method was employed to assess the impact strength among the factors.The DEMATEL method was applied to calculate the centrality,cau5 sality,influence,and being influenced degrees of the influencing factors.The ISM method was used to construct a hierarchical structure of the influencing factors related to medical surge risks,thereby revealing the connections and interaction mechanisms among these factors.Results Seven critical influencing factors were identified,including the crisis decision-making capacity and leadership effectiveness of emergency managers,the completeness of the emer5 gency system and dynamic execution capabilities,and the cross-departmental coordination mechanism and com5 mand collaboration efficiency.Deep driving factors and coupling pathways were also revealed.Conclusion The risk of medical surges exhibits multi-factorial coupling cascade effects;attention should be directed towards the construc5 tion of mid-to-deep level mechanisms such as information systems,institutional frameworks,and organizational management,to enhance targeted capabilities and systemic resilience in risk governance.

Objective To define the conceptual connotation of network dynamic collaboration capacity in medical surge response and construct its theoretical model.Methods A mixed concept analysis method was employed,integrating multidisciplinary literature and collecting empirical evidence through semi-structured expert interviews to extract the concept of network dynamic collaboration capacity in medical surge response.By integrating complex systems,network science,synergetics,and dynamic capability theory,and combining the interview results,the study used the analogy of flood control in hydraulic engineering to develop a"network-dynamic-collaboration"triangular capacity theoretical model.Results It reveals one antecedents(sudden external shocks have led to an abnormal and continuous surge in medical demand),six core attributes(information interconnection accessibility,dynamic resource adaptability,risk perception responsiveness,multi-party collaborative interactivity,service process adaptability elasticity,and learning iterative evolution),and four consequences(mitigation of crowding risk,protection of service continuity,minimization of crisis spillover,and enhancement of system resilience)for the network dynamic collaboration capacity in medical surge response.The theoretical model elucidates the coupling mechanisms among network structural resilience,dynamic regulation processes,and collaborative co-evolution in resisting medical surge.Conclusion The new concept and theoretical model proposed in this study deepen the understanding of medical surge response system mechanisms and offer a theoretical framework and practical guidance for strengthening the full-chain resilience of health emergency systems.

Objective To empirically analyze multiple pathways for enhancing medical surge response capacity and provide useful references for improving the resilience of health systems.Methods A comprehensive theoretical analysis framework for improving medical surge response capacity was constructed based on the 4S theory and collaborative governance theory.68 interview texts on medical surge response capacity conducted in July 2024 were selected as analysis samples.Using fuzzy-set Qualitative Comparative Analysis(fsQCA),7 conditional variables were selected from four dimensions:management system,information system,materials,and personnel to analyze their impact on medical surge response capacity.Results(1)A single conditional variable does not constitute a necessary condition for improving medical surge response capacity;(2)After the combination of conditions,8 specific configuration paths for capacity improvement were identified.Through systematic and comprehensive refinement,they were summarized into three modes of comprehensive configuration capacity improvement paths,namely:rapid response and collaborative operation mode,information empowerment and precise response mode,and resource conditions and resilience construction mode.Conclusion It is necessary to explore and construct systematic,combined,modularized and path-oriented capacity building strategies,refine the operational implementation paths for improving China's medical surge response capacity,target the linkage and configuration modes of different conditional variables,promote the formulation and implementation of modular construction schemes oriented by key capacity,and make efforts from multiple aspects to enhance the resilience of the health system.

OBJECTIVE To investigate the clinical characteristics of drug-induced liver injury （DILI） induced by glucagon- like peptide-1 receptor agonists （GLP-1RAs）， and to provide a reference for safe clinical medication. METHODS Using search terms such as “GLP-1”“GLP-1RAs”“semaglutide” “drug-induced liver injury”， relevant studies from PubMed， Embase， the Cochrane Library， CNKI， Wanfang Data and VIP were retrieved. Descriptive analysis was performed on cases of DILI induced by GLP-1RAs. RESULTS A total of 11 studies， comprising 11 patients， were included. Among them， 4 were male （36.4%） and 7 were female （63.6%）. Patient ages ranged from 17 to 64 years； 5 patients （45.5%） were between 50 and 65 years old. Six patients were treated for diabetes， and five for weight loss. Ten patients had underlying diseases. The shortest time to the onset of DILI was 5 days after medication， while the longest was approximately 180 days. The DILIs induced by GLP-1RAs were mainly hepatocellular injury type （6 cases）； severity levels included severe （3 cases）， moderate （6 cases）， and mild （2 cases）. Gastrointestinal symptoms and jaundice were the most common clinical manifestations. The association between DILI and GLP- 1RAs was assessed as “probable” in 10 cases and “possible” in 1 case. All 11 patients improved after drug discontinuation and （or） corresponding treatment. CONCLUSIONS DILI induced by GLP-1RAs is relatively concentrated in patients aged 50-65， with a higher incidence in females. The risk may be further increased in patients with underlying diseases. Clinical use of these agents should enhance pharmaceutical care， including identification of high-risk populations and patient education （especially symptom recognition）. When relevant symptoms appear， the drug should be discontinued immediately， with liver-protective therapy initiated when necessary， to ensure patient safety of drug use.

Objective:To explore the mechanisms of oxaliplatin resistance mediated by TET2 methylation in the treatment of acute lymphoblastic leukemia (ALL) using bioinformatics methods.Methods:The data on drug-resistant and sensitive cell lines related to oxaliplatin treatment for ALL were download using the Genomics of Drug Sensitivity in Cancer (GDSC) database (updated in December 2023); the drug-resistant cell lines were screened based on half maximal inhibitory concentration ( IC50) > 10 μmol/L, and the difference in IC50 between drug-resistant and sensitive cell lines were analyzed using Mann-Whitney U test. The cancer driver mutation genes in drug-resistant cell lines were retrieved using the Cancer Cell Line Encyclopedia (CCLE) database (updated in December 2023). Using the protein-protein interaction (PPI) network functional enrichment analysis (STRING) database (updated in June 2024), PPI network analysis was performed on cancer driver mutation genes with biological functions. A confidence threshold of ≥ 0.7 (high confidence) and an average network node degree above 4 (high average) were selected to screen for cancer driver mutation genes with significant biological functions. Using the microRNA Data Integration Portal (mirDIP) database (updated in June 2024), the coexpression data of microRNA (miRNA) and mutant target genes were queried, miRNA-target gene pairs were screened according to the highest score threshold of 1% miRNA and interaction score > 0.9, and the regulatory effect of miRNA on mutant genes was analyzed. DNA methylation data were download from the Methylation in Human Cancer (MethHC) database (updated in June 2024) and the methylSig R software package was used to analyze the differentially methylated regions (DMR) of DNA methylation between drug-resistant and sensitive cell lines; genes with P < 0.05 and absolute difference > 0.2 were selected, and they were divided into high methylation gene group and low methylation gene group. Spearman correlation analysis and Spearman rank test were performed for the degree of methylation and gene expression, and the key genes with P < 0.01 were screened to reveal the relationship between methylation degree and gene expression. Results:As a result of searching the GDSC database, there were a total of 9 drug-resistant cell lines and 17 sensitive cell lines related to oxaliplatin treatment for ALL; after Z-score normalization of IC50 data between drug-resistant and sensitive cell lines, the average rank of drug-resistant cell lines was 21, and the average rank of sensitive cell lines was 8.5, with a statistically significant difference ( Z = -4.08, P < 0.01). Eight cancer driver mutation genes with significant biological functions that lead to drug resistance of the cell lines were screened using the CCLE database and STRING database. According to the mirDIP database, there were a total of 12 pairs of miRNA-target gene pairs with miRNA-target gene interaction scores >0.9. miRNA had strong regulatory effects on the expressions of NRAS and MAP2K1 target genes. In the MethHC database, the β values (numerical value of increased methylation level) of DMR for genes such as TP53, RXRG and SGIP in drug-resistant cell lines were 0.151, 0.165 and 0.149, respectively, compared to those in sensitive cell lines, the differences were statistically significant (all P < 0.01). The degree of methylation of SGIP gene was negatively correlated with the relative expression level of SGIP mRNA ( r = -0.71, P < 0.01), and SGIP gene underwent high methylation at promoter site 143886940. The cg08321569 locus in the TET2 gene domain of drug-resistant cell lines exhibited persistent high methylation, with a methylation level of β = 0.89. This locus was located 1.2 kb downstream of the transcription start point of exon 4, and the degree of TET2 methylation was negatively correlated with the relative expression level of TET2b mRNA ( r = -0.81, P < 0.01). Conclusions:TET2 methylation may be an important factor for oxaliplatin resistance in the treatment of ALL.

Objective:To construct a classification management model on the basis of Kraljic matrix for electrocardiogram(ECG)monitoring equipment in emergency intensive care unit(ICU),so as to explore its application value in the management for ECG monitoring equipment in emergency ICU.Methods:The classification management model on the basis of index for ECG monitoring equipment in emergency ICU was constructed.According to two classification dimensions included the market supply risk and the self-value,an indicator system of classification management,which aimed at strategic materials with high value and high risk,leverage materials with high value and low risk,bottleneck materials with low value and high risk,and conventional materials with low value and low risk,was constructed.A total of fifty-one ECG monitoring equipment in the emergency ICU of The People's Hospital of Longhua of Shenzhen from January to December 2023 were selected,and they were managed respectively by conventional management mode(25 sets)and classification management mode(26 sets)according to different management modes.The standardization level of operation management for equipment,the occurrence of safety risk and the level of management for equipment of the two management modes were compared,and the satisfaction of 30 relative personnel,who used and managed these equipment,for classification management of equipment also were compared.Results:The average values of the percentage of standardization level of normality of equipment operation,disinfection and sterilization,maintenance and fault repair of using classification management mode were respectively(91.58±4.33)%,(92.1±3.28)%,(91.49±3.54)%and(92.58±3.32)%,all of which were higher than those of conventional management mode,and the differences were statistically significant(t=12.537,15.706,14.196,18.946,P<0.05),repsectively.The average incidences of the risk of pressure injury,electrical injury and body fluid extravasation of adopting classification management mode were respectively(2.54±0.87)%,(3.02±0.82)%and(1.29±0.65)%,all of which were lower than those of adopting conventional management mode,and the differences were statistically significant(t=22.825,17.453,24.424,P<0.05),respectively.The satisfaction scores of 30 relative management personnel,who used equipment on the process rationality,system standardization and quality effectiveness,of adopting classification management mode were respectively(94.26±3.54),(92.57±4.36)and(91.87±3.69),all of which were higher than those of conventional management mode,and the differences were statistically significant(t=14.052,13.991,13.551,P<0.05),respectively.The reasonable placement rate,recording rate of standardization,and intact rate of equipment in the 26 equipment by adopting classification management mode were respectively 92.31%,92.31%and 88.46%,all of which were significantly higher than those by adopting conventional management mode,and the differences were statistical significant(x2=12.052,10.398,11.338,P<0.05).Conclusion:The classification management model of ECG monitoring equipment in emergency ICU can increase the management efficiency for the equipment in operating room of hospital,and improve the operation quality of equipment,and enhance the safety of equipment in clinical use,and the standardization of operation management for equipment.