Multidrug-resistant (MDR) bacterial infections have emerged as a serious challenge of global public health crisis. The overuse and misuse of conventional antibiotics have dramatically accelerated the emergence, evolution and worldwide spread of drug-resistant bacterial strains, necessitating urgent exploration of novel antibacterial strategies. Bacteriophages serve as natural bacterial predators offering distinct advantages including high host specificity, autonomous self-replication capabilities and cost-effective large-scale production. However, wild-type phages present significant clinical limitations due to their narrow host ranges, susceptibility to rapid immune clearance and poor penetration of bacterial biofilms, which severely restrict their therapeutic applications. The convergence of synthetic biology, nanotechnology and advanced gene editing technologies has accelerated the development of engineered bacteriophage platforms, providing programmable, scalable and clinically translatable pathways to overcome these inherent biological constraints. Here, we systematically delineate four fundamental strategies for engineered bacteriophage development. Chemical modification utilizes reactive functional groups such as amino, carboxyl and thiol moieties on capsid proteins through esterification, amidation or click chemistry reactions to achieve precise drug conjugation and surface functionalization. In vivo editing encompasses ultraviolet or chemical mutagenesis for random mutation induction, homologous recombination for targeted genetic alterations, recombineering methodologies including electroporation-mediated bacteriophage recombination engineering, and CRISPR-Cas systems for precise genome editing to enable exact genetic reconstruction and host range reprogramming. In vitro synthesis leverages genome engineering platforms where intact phage genomes are transferred into yeast or host bacteria to facilitate highly efficient homologous recombination, enabling large DNA fragment assembly and cross-gene host range expansion without bacterial toxicity constraints. Directed evolution combines artificial selection through mutation library screening with rational design approaches involving chimeric receptor binding protein construction or site-specific mutagenesis, effectively balancing the discovery of unknown adaptive pathways with targeted host specificity modification. Moreover, we comprehensively discuss therapeutic applications across diverse clinical scenarios. Engineered bacteriophage effectively disrupt bacterial biofilms through sophisticated functionalized delivery platforms including nanozyme-conjugated phages, phage-liposome nanoconjugates and bio-responsive hydrogels, demonstrating significantly enhanced bactericidal efficiency compared to unmodified free phages. These bioengineered vectors attenuate bacterial virulence and resensitize pathogens to antibiotics by delivering CRISPR-Cas systems or base editors to disrupt critical virulence factors such as pili, capsule synthesis machineries and quorum sensing systems, or by inactivating antibiotic resistance determinants including beta-lactamase genes. As an intelligent nanomedicine delivery platform, engineered bacteriophage enable precise pathogen elimination an through photocatalytic reactive oxygen species generation, immunomodulatory interventions, or controlled release of antibacterial drugs. Furthermore, oral administration of engineered bacteriophage facilitates microbiota modulation, which selectively eliminate intestinal pathogens while preserve beneficial commensal microbiota, thereby restoring microbial community balance and preventing complications associated with dysbiosis. Finally, we critically analyze persistent challenges including host strain matching complexity, evolution of bacterial resistance mechanisms, pharmacokinetic optimization requirements, optimal administration route selection, large-scale production quality control standards and clinical dosing determination protocols. Through multidisciplinary integration of synthetic biology, infectious disease medicine and immunology, future translational medicine studies of bacteriophage should establish comprehensive technical platforms encompassing rapid phage screening, intelligent rational design, rigorous in vivo evaluation and standardized clinical validation processes, ultimately advancing engineered bacteriophage from laboratory innovations to clinically approved therapeutics for effectively combating MDR bacterial infections.

Objective To gain insights into the biological characteristics of different populations of Culex tritaeniorhynchus within and around the Yellow Sea wetland from the perspective of the occurrence of resistance, we investigated the levels of resistance to deltamethrin and kdr gene mutation in the wetland and its peripheral areas. Methods Specimens were collected from Cx. tritaeniorhynchus populations at two monitoring sites in the Rare Bird National Nature Reserve and Tiaozi Ni Wetland Scenic Area, and also from two populations in Yancheng City and the Liuhe District of Nanjing, and the resistance of these mosquitoes to deltamethrin was determined using the CDC biotest bottle method. For each concentration of deltamethrin assessed, a random subset of exposed specimens was selected for amplification of the kdr gene fragment, followed by Sanger sequencing to identify and analyze resistance-associated mutations. Results The LC50 levels of deltamethrin among mosquitoes from the four populations in Luhe, Yancheng, the Rare Bird National Nature Reserve and the Tiaozi Ni Wetland Scenic Area were 2.048 5, 7.798 2, 3.473 3, and 17.695 5 mg/mL, respectively, with corresponding concentrations of deltamethrin ranging from 0.005 to 5.000,0.050 to 50.000,0.050 to 25.000 and 0.050 to 50.000 mg/mL, respectively. Furthermore, the ranges of the KT50 values were 11.76-107.43, 67.05-216.30,29.77-107.43 and 28.40-329.51 min; the 1-h knockdown rates were 34.58%-99.15%, 9.52%-43.80%, 55.09%-73.01%, and 10.09%-68.07%; and the 24-h mortality rates were 12.15%-67.52%,9.52%-79.56%,13.17%-82.21%, and 11.01%-78.99%, respectively. With respect to kdr gene mutation, we assayed a total of 63,70,59, and 57 mosquitoes for the four populations, for which we detected L1014F mutation frequencies of 14.29%, 35.00%, 20.34%, and 31.58%, respectively, with a majority of these mutations being heterozygous for resistance. In addition, five adult mosquitoes were identified has having synonymous mutations at site 1011[i. e. , AAT(asparagine)mutation to AAC(asparagine)]. Conclusions Our findings revealed the clear resistance of Cx. tritaeniorhynchus to deltamethrin in the Yancheng region of the Yellow Sea wetland, and the resistance phenotype and kdr frequency of Cx. tritaeniorhynchus in the wetland environment were comparable to those of Cx. tritaeniorhynchus in the wetland environment, thereby indicating that the resistance of different populations of Cx. tritaeniorhynchus was homogeneous under the pressure of different insecticide selection within and around the wetland. However, the underlying mechanisms need to be further studied.

Based on LI Gao's theory of "heavy obstruction" and "blockage of the nine orifices"， this paper proposes the pathological concept of "heavy obstruction and orifice blockage". It is suggested that the core pathogenesis of functional constipation （FC） lies in simultaneous sinking of spleen and lung， together with accumulation and obstruction of dampness and turbidity， resulting in impaired movement of intestinal qi. Within this framework， spleen deficiency with sinking of dampness is considered as the primary pathological mechanism of outlet obstructive constipation （OOC）， while sinking of lung qi is regarded as the key mechanism underlying slow transit constipation （STC）. When both pathological mechanisms coexist， mixed constipation （MC） develops. Guided by this theory， FC is classified into three patterns for syndrome-based treatment. OOC is treated by promoting bowel movement， descending turbid pathogens， and opening the orifices to restore function， with self-formulated Shengxian Tongqiao Decoction （升陷通窍汤）. STC is treated by diffusing lung qi， regulating spleen function， raising sinking qi， and promoting transportation， with self-formulated Xuanfei Yunpi Decoction （宣肺运脾汤）. MC is treated by regulating lung and spleen function， simultaneously raising clear qi and descending turbidity， with self-formulated Xuanyun Tongqiao Decoction （宣运通窍汤）. In clinical practice， modifications should be made according to accompanying syndromes and individual conditions.

Based on LI Gao's theory of "heavy obstruction" and "blockage of the nine orifices"， this paper proposes the pathological concept of "heavy obstruction and orifice blockage". It is suggested that the core pathogenesis of functional constipation （FC） lies in simultaneous sinking of spleen and lung， together with accumulation and obstruction of dampness and turbidity， resulting in impaired movement of intestinal qi. Within this framework， spleen deficiency with sinking of dampness is considered as the primary pathological mechanism of outlet obstructive constipation （OOC）， while sinking of lung qi is regarded as the key mechanism underlying slow transit constipation （STC）. When both pathological mechanisms coexist， mixed constipation （MC） develops. Guided by this theory， FC is classified into three patterns for syndrome-based treatment. OOC is treated by promoting bowel movement， descending turbid pathogens， and opening the orifices to restore function， with self-formulated Shengxian Tongqiao Decoction （升陷通窍汤）. STC is treated by diffusing lung qi， regulating spleen function， raising sinking qi， and promoting transportation， with self-formulated Xuanfei Yunpi Decoction （宣肺运脾汤）. MC is treated by regulating lung and spleen function， simultaneously raising clear qi and descending turbidity， with self-formulated Xuanyun Tongqiao Decoction （宣运通窍汤）. In clinical practice， modifications should be made according to accompanying syndromes and individual conditions.

AIM To sequence the chloroplast genome of Artemisia vestita Wall.ex Bess.METHODS Based on ethnobotanical surveys,sample collection and original plant identification were carried out.The chloroplast genome was sequenced using the Illumina platform,followed by assembly and annotation.A comprehensive comparative analysis was conducted with six Artemisia species.The maximum likelihood(ML)phylogenetic tree was constructed based on the chloroplast genome sequences of A.vestita and 32 other Asteraceae species,with Leptocodon hirsutus D.Y.Hong of Campanulaceae as outgroup.RESULTS The chloroplast genome of A.vestita was 151 204 bp in length,including a small single-copy region of 18 331 bp,a large single-copy region of 82 949 bp,and inverted repeat regions of 24 962 bp,with a total GC content of 37.45％.134 genes were annotated,including 89 protein-coding genes,8 ribosomal RNA genes,and 37 transfer RNA genes.A total of 67 SSRs and 44 LSRs were detected in the chloroplast genome.Comparative analysis with closely related species of Artemisia revealed 3 highly variable genes(clpP,rpl36,ycf1)and 6 highly variable intergenic regions(trnK-UUU-matK,rps18-rpl20,rpl36-infA,rpl14-rpl16,rpl16-rpl3 and trnL-UAG-ccsA),which could serve as candidate DNA barcodes for Artemisia identification.Phylogenetic analysis showed that Artemisia formed a highly supportive monophyletic group,with A.vestita and A.gmelinii Web.ex Stechm.being closely related.CONCLUSION This study may provide fundamental data for phylogenetic analysis of Artemisia,taxonomic identification and DNA barcoding construction of Tibetan herb.

The detection rate of thyroid nodules has gradually increased in recent years.Comprehensive and accurate preoperative evaluation and early identification of risk factors help doctors to choose treatment options and improve prognosis.Radiomics extracts quantitative features from medical images for evaluation of thyroid nodules through high-throughput mining of invisible image features,which has been widely used and has excellent performance in the identification of benign and malignant thyroid nodules,lymph node metastasis,extrathyroidal extension,molecular biological changes,recurrence and prognosis of thyroid cancer.However,there are also shortcomings such as large differences in performance among models from different institutions.This article reviews the application value,limitations and future development prospects of radiomics in the thyroid nodules,so as to provide new ideas for clinical practice and research.

AIM To sequence the chloroplast genome of Artemisia vestita Wall.ex Bess.METHODS Based on ethnobotanical surveys,sample collection and original plant identification were carried out.The chloroplast genome was sequenced using the Illumina platform,followed by assembly and annotation.A comprehensive comparative analysis was conducted with six Artemisia species.The maximum likelihood(ML)phylogenetic tree was constructed based on the chloroplast genome sequences of A.vestita and 32 other Asteraceae species,with Leptocodon hirsutus D.Y.Hong of Campanulaceae as outgroup.RESULTS The chloroplast genome of A.vestita was 151 204 bp in length,including a small single-copy region of 18 331 bp,a large single-copy region of 82 949 bp,and inverted repeat regions of 24 962 bp,with a total GC content of 37.45％.134 genes were annotated,including 89 protein-coding genes,8 ribosomal RNA genes,and 37 transfer RNA genes.A total of 67 SSRs and 44 LSRs were detected in the chloroplast genome.Comparative analysis with closely related species of Artemisia revealed 3 highly variable genes(clpP,rpl36,ycf1)and 6 highly variable intergenic regions(trnK-UUU-matK,rps18-rpl20,rpl36-infA,rpl14-rpl16,rpl16-rpl3 and trnL-UAG-ccsA),which could serve as candidate DNA barcodes for Artemisia identification.Phylogenetic analysis showed that Artemisia formed a highly supportive monophyletic group,with A.vestita and A.gmelinii Web.ex Stechm.being closely related.CONCLUSION This study may provide fundamental data for phylogenetic analysis of Artemisia,taxonomic identification and DNA barcoding construction of Tibetan herb.

Objective To investigate the role of Insulin like growth factor 2 mRNA binding protein 1(IGF2BP1)and long non-coding RNA LINC00160(LINC00160)in gastric cancer,and its potential mechanism of regulating the proliferation and invasion of gastric cancer cells.Methods Quantitative real time polymerase chain reaction(qRT-PCR)was used to detect the expression level of LINC00160 in gastric cancer tissues and cells.Bioinformatics prediction,RNA-binding protein immunoprecipitation(RIP)and methylated RNA immunoprecipitation(MeRIP)were used to verify the binding effect of LINC00160 and IGF2BP1.The correlation between the expression of LINC00160 and IGF2BP1 in gastric cancer tissues was analyzed by Pearson assay.CCK-8 assay and Transwell assay were used to detect cell proliferation and invasion.The changes of aerobic glycolysis index[glucose intake,lactate production,and Adenosine-triphosphate(ATP),extracellular acidification rate(ECAR)and oxygen consumption rate(OCR)]were detected and analyzed.Results Compared with normal tissues,the expression of LINC00160 in gastric cancer tissues(5.13±0.62 vs 1.02±0.03)was significantly up-regulated,and the difference was statistically significant(t=-36.266,P<0.001).The expression level of LINC00160 in gastric cancer cells was higher than that of human normal gastric epithelial cell line GES-1,and the difference was statistically significant(F=24.595,P<0.001).Compared with the control group,silenting LINC00160 significantly inhibited the proliferation(0.42±0.03 vs 1.03±0.04)and invasion(22.13%±1.97%vs 42.15%±2.67%)of AGS cells,decreased glucose uptake(2.11±0.26mmol/L vs 4.22±0.37mmol/L)and lactate production(6.84±1.25mmol/L vs 11.68±1.55mmol/L),decreased ECAR,and increased ATP(3.34±0.29mmol/L vs 1.87±0.24mmol/L)levels and OCR,and the differences were statistically significant(t=4.188～24.423,all P<0.01).The expression of IGF2BP1 protein in gastric cancer tissues(4.07±0.36)was significantly higher than that in adjacent tissues(1.01±0.03),and the difference was statistically significant(t=-46.396,P<0.01),and was positively correlated with the expression of LINC00160(r2=0.774 5,P<0.01).Mechanistic studies revealed that IGF2BP1 upregulated LINC00160 expression by binding m6A modified LINC00160 to promote its stability.Silencing IGF2BP1 significantly inhibited the expression of LINC00160 and the proliferation,invasion and aerobic glycolysis of gastric cancer cells,and the differences were statistically significant(t=4.386～11.989,all P<0.01).Overexpression of LINC00160 reversed the effect of IGF2BP1 silencing on AGS cells.Conclusion LINC00160 is significantly up-regulated in gastric cancer,and IGF2BP1 may stably regulate the expression of LINC00160 through m6A modification,promote the aerobic glycolysis of tumor cells,and participate in the occurrence and development of gastric cancer.

Objective To investigate the clinical efficacy and safety of facilitated percutaneous coronary intervention(PCI)with half-dose recombinant staphylokinase(r-SAK)in patients with ST-segment elevation myocardial infarction(STEMI)who are expected to undergo PCI within 120 minutes.Methods From October 2021 to August 2022,a total of 200 STEMI patients in eight centers were included and randomly assigned in a 1﹕1 ratio to either r-SAK group or control group.Patients received loading doses of aspirin and ticagrelor and intravenous heparin and were randomized to receive an intravenous bolus of either 5 mg r-SAK or normal saline prior to PCI.The outcomes were set as ST-segment resolution(STR)at 60-90 minutes after PCI,the proportion and transition of pathological Q waves on the 5th day after PCI,and the proportion of high-sensitivity cardiac troponin T(hs-cTnT)peaking within 12 hours of onset.The safety outcome was major bleeding events defined as Bleeding Academic Research Consortium(BARC)≥type 3 bleeding during hospitalization.Results Compared with the control group,the r-SAK group had a higher proportion of STR≥70%within 60-90 minutes after PCI(58.3%vs.40.3%,P=0.009);a lower proportion of pathological Q waves(59.1%vs.74.1%,P=0.040);a lower rate of Q wave progression(14.8%vs.43.2%,P＜0.001);a higher rate of Q wave disappearance(12.5%vs.3.7%,P=0.027);and a higher proportion of hs-cTnT peaking within 12 hours of symptom onset[31/40(77.5%)vs.17/33(51.5%),P=0.027].Regarding the safety outcome,no significant difference in BARC≥type 3 bleeding was found between the two groups during hospitalization(P＞0.05).Conclusions For STEMI patients who were expected to undergo primary PCI within 120 minutes of symptom onset,the facilitated PCI with half-dose r-SAK significantly increased the proportion of STR≥70%at 60-90 minutes after PCI,reduced the formation of pathological Q waves,and shortened the time to peak hs-cTnT,without increasing the risk of bleeding,which should be an alternative reperfusion strategy worthy of further study.

Objective:To evaluate the efficacy and feasibility of a domestically developed robotic surgical system based on fiber-optic dedicated line communication in cross-regional urological telesurgery.Methods:This was multicenter，single-arm，retrospective case series study. The data of patients who underwent urological telesurgeries using the telesurgical system between January 2023 and December 2024 were analyzed. The cohort included 59 patients from seven hospitals across China. Among the patients，47 were male（79.7%）and 12 were female（20.3%），with a median age of 63.0（56.0，68.0）years and a body mass index of（24.7 ± 3.0）kg/m 2. Surgical procedures included 32 radical prostatectomies，24 partial nephrectomies，one radical nephrectomy，one adrenalectomy，and one ureteral reconstruction. The perioperative indicators，pathological results and postoperative complications were analyzed. The network monitoring data were collected，and the perioperative data of patients，remote system monitoring data and costs were compared between the two communication modes of optical transport network（OTN）and cloud-connect network（CCN）. Results:All 59 remote surgeries were successfully completed，with a mean operative time of（138.0 ± 54.0）minutes，median intraoperative blood loss of 50.0（30.0，100.0）ml and a postoperative hospital stay of 5.0（4.0，6.0）days. No cases required reoperation，Clavien-Dindo grade ≥3 complications，or readmission. The geographical distance between the primary and remote surgical sites ranged from 450 to 2 800 km. Network monitoring revealed increased bidirectional latency with distance increasing：the shortest latency time（Hefei-Hangzhou，450 km）was（16.59 ± 0.80）ms，while the longest（Harbin-Hangzhou，2 200 km）latency time was（53.31 ± 0.31）ms. Average frame loss per procedure was 0?1.27 frames. The results of subgroup analysis comparing OTN and CCN communication modes showed no significant differences in operative time［（130.7 ± 70.5）minutes vs.（142.1 ± 42.9）minutes， P = 0.442］，postoperative hospitalization［6.0（4.0，8.0）d vs. 5.0（4.0，6.0）d， P = 0.581］，or readmission rates（0 vs. 0）. However，CCN demonstrated significant cost advantages with 500 RMB per operation vs. 3 000 RMB per operation for OTN. Conclusions:Urological telesurgery using fiber-optic communication is feasible. The CCN mode，with its cost-effectiveness，excellent usability，and multi-point interconnection flexibility，is currently the preferred communication model for telesurgical applications.