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.

Objective To analyze mosquito species composition and prevalence of pathogens carried by mosquitoes in Jiangsu Province from 2020 to 2024 and to provide a scientific basis for the prevention and control of mosquito-borne diseases. Methods Mosquitoes were collected using CO2-baited traps. The presence of mosquito-borne pathogens including dengue virus, Japanese encephalitis virus, yellow fever virus, West Nile virus, Chikungunya virus, and Sindbis virus was tested using commercial kits for fluorescence-based quantitative PCR. Results The most prevalent mosquito species found across different regions of Jiangsu Province were Culex pipiens pallens and Cx. tritaeniorhynchus, accounting for 81.35% to 93.01% of the total, followed by Armigeres subalbatus and Anopheles sinensis, which comprised 5.89% to 15.85% of the total. The densities of other monitored mosquito species were relatively low. Pathogen detection revealed that, only Cx. tritaeniorhynchus tested positive for Japanese encephalitis virus nucleic acid, whereas the remaining four mosquito species tested negative for the nucleic acids of all other six pathogens. The overall positivity rate of Japanese encephalitis virus (JEV) in Cx. tritaeniorhynchus showed an initially increasing trend followed by a decrease and a subsequent increase. The peak detection rate occurred in 2021 (11.93%), with a much lower positive rate of 0.80% in 2023. Genotyping result revealed that all JEV strains in Jiangsu Province belonged to the G1 genotype and were genetically closest to the strain Shangdong08DY.29 (MN072875.1). Conclusions The incidence of Japanese encephalitis virus carried by mosquito, especially Cx. tritaeniorhynchus, in Jiangsu Province shows an upward trend, requiring sustained surveillance. A variety of monitoring method should be adopted to survey mosquitoes across different habitats, ensuring the accuracy and comprehensiveness of the monitoring result.

Objective To investigate the species composition, distribution, density, and pathogen-carrying status of host-seeking ticks in urban environments of Jiangsu Province, and to provide a scientific basis for the prevention and control of tick-borne diseases in urban settings. Methods From April to September 2023, a survey on host-seeking ticks was conducted in three types of habitats (city parks, residential areas, and street greenbelts) across 54 counties (cities, districts) of 13 prefecture-level cities in Jiangsu Province by using the flagging method. RStudio 4.4.3 (Windows version) was employed to perform chi-square test analysis on the species composition of ticks across different months, and Friedman test (for multiple paired samples) was applied to analyze monthly changes in the average tick density index among different habitats. Quantitative real-time PCR was performed to detect pathogens in the captured ticks. Results A total of 863 host-seeking ticks were captured from 54 habitats in 24 counties (cities, districts) of 11 prefecture-level cities (Nanjing, Wuxi, Changzhou, Suzhou, Nantong, Huai'an, Yancheng, Yangzhou, Zhenjiang, Taizhou, and Suqian) in Jiangsu Province, whereas no ticks were captured in Xuzhou and Lianyungang. The collected ticks belonged to three species, with Haemaphysalis longicornis being the dominant species (accounting for 82.62%), followed by Haemaphysalis flava and Hae. phasiana. The average density index of ticks in positive habitats was 3.20 ticks/ (flag·100 m). In terms of tick density among prefecture-level cities, Wuxi had the highest density[13.55 ticks/(flag·100 m)], whereas Nanjing and Taizhou had the lowest[both,0.20 ticks/(flag·100 m)]. With respect to the types of positive habitats,46 positive city parks,7 positive residential areas, and 1 positive street greenbelt were found, with the average tick density index being 3.46, 1.86, and 3.60 ticks/flag · 100 m, respectively. No statistically significant differences were observed in the monthly variations in the average tick density index among different habitats (P＞0.05). Pathogen detection showed no Bandavirus dabieense, Rickettsia, or Borrelia burgdorferi in the collected ticks. Conclusions Host-seeking ticks have established populations in urban environments across most prefecture-level cities in Jiangsu Province, with Hae. longicornis identified as the dominant species. City parks serve as the primary breeding habitats for these ticks. Strengthening tick surveillance and control measures in densely populated and frequently visited areas, such as city parks and residential neighborhoods, is crucial for the effective prevention and control of urban tick-borne diseases.

Xanthine oxidase (XO) is an important therapeutic target for the treatment of hyperuricemia and gout. Based on the previously identified potent XO inhibitor 1, seventeen oxadiazoles and their ring-opening analogues were designed and synthesized via the bioisostere replacement strategy. Among them, compounds 2l, 2n, and 3b showed obvious XO inhibitory activity at the concentration of 10 μmol·L^-1, and compound 3b exhibited an IC₅₀ value of 1.45 μmol·L^-1.

AIM To investigate the effects of Yunpi Tongchang Formula on intestinal mucosal barrier damage in rats with opioid-induced constipation(OIC)of Spleen-Kidney Yang Deficiency Syndrome.METHODS In contrast to the 10 rats of the blank group,the 50 rats of the modeling group were induced into models of OIC of Spleen-Kidney Yang Deficiency Pattern by 7 days consecutive administration of both subcutaneous loperamide injection and alternating gavage of activated carbon ice water and vinegar.Following successful modeling,rats were randomly allocated into the model group,the mosapride citrate tablet group(1.35 mg/kg),and the high-dose,medium-dose,and low-dose Yunpi Tongchang Formula groups(15.12,7.56,3.78 g/kg),with 8 mice in each group.Upon the completion of the 14 days treatment,the rats had their TCM Syndrome scores assessed;their fecal water content,initial black stool excretion time,and small intestine propulsion rate measured;their colon tissue morphology observed by HE staining;their serum levels of IL-6,TNF-α,and IL-1β detected by ELISA;their expressions of occludin and zonula occludens-1(ZO-1)in colon tissues detected by immunohistochemistry;their mRNA expressions of MyD88,TLR4 and NF-κB p65 in the colon tissues detected by RT-qPCR;and their protein expressions of MyD88,TLR4 and NF-κB p65 in the colon tissues detected by Western blot.RESULTS Compared to the blank group,the model group had higher TCM Syndrome scores(P＜0.01);lower fecal water content and small intestine propulsion rate(P＜0.05,P＜0.01);longer initial black stool excretion time(P＜0.01);more mucosal edema in colon tissue,obvious inflammatory infiltration,and glandular disorder;increased serum levels of IL-6,TNF-α and IL-1 β(P＜0.05);decreased colon expressions of ZO-1 and occludin(P＜0.01);and increased mRNA and protein expressions of TLR4,MyD88 and NF-κB p65(P＜0.01).Compared to the model group,both the medium-dose Yunpi Tongchang Formula group and the mosapride citrate tablet group demonstrated effectively reduced TCM syndrome scores(P＜0.01);increased fecal water content and small intestine propulsion rate(P＜0.05,P＜0.01);and shorter initial black stool excretion time(P＜0.01);improved colon mucosal edema and inflammatory infiltration;decreased serum levels of IL-6,TNF-α and IL-1β(P＜0.01);upregulated protein expressions of ZO-1 and occludin(P＜0.01);and downregulated mRNA and protein expressions of TLR4,MyD88 and NF-κB p65(P＜0.05,P＜0.01).CONCLUSION Yunpi Tongchang Formula significantly ameliorates constipation symptoms in OIC rat models of Spleen-Kidney Yang Deficiency Syndrome because of its efficacy in attenuating intestinal inflammation and preserving the integrity of intestinal epithelial barrier structure,with its mechanistic action in downregulating TLR4/MyD88/NF-κB signaling pathway activation.

With the rapid development of competitive sports, the incidence of anterior cruciate ligament (ACL) injury is on the rise. Such injuries may shorten athletes′ career and lead to other long-term adverse consequences. Although athletes generally recover well after ACL reconstruction, many still struggle to return to their pre-injury performance levels. Advances in the understanding of ACL anatomy and injury mechanisms, along with the evolution of surgical techniques and rehabilitation methods, have provided more individualized and tailored options for athletes following ACL injuries. However, there is currently no consensus in China regarding surgical and rehabilitation strategies for competitive athletes aiming to return to sports after ACL injuries. To this end, the Sports Medicine Committee of the Chinese Research Hospital Association and the Editorial Board of the Chinese Journal of Trauma jointly formulated the Expert consensus on surgical treatment and rehabilitation for competitive sports athletes returning to sports after anterior cruciate ligament injury ( version 2025), and presented 14 recommendations covering surgical indications, preoperative rehabilitation, surgical timing, surgical strategies and postoperative rehabilitation strategies, aiming to improve the surgical treatment and rehabilitation system for ACL injuries in competitive athletes and facilitate their return to high-level sports performance after injury.

Systemic lupus erythematosus(SLE)is a chronic diffuse connective tissue disease characterized by abnormal activation of the immune system,which attacks the body's tissues.It has a complex course and its pathological basis is vasculitis.In recent years,research on the relationship between SLE and the gut microbiota has increased significantly,but how to regulate the gut microbiota for the treatment of SLE remains unclear.Studies have found that the intestinal microbiota of SLE patients differs from that of healthy people in terms of Firmicutes,Bacteroidetes,Actinomycetes,and Proteobacteria,etc.,and this has been verified in animal experiments.In this review,the changes of intestinal microbiota in SLE patients and their association with the pathogenesis and progression of the disease are systematically reviewed,aiming to provide new insights into the treatment of SLE.

Objective To explore the predictive value of automated breast ultrasound(ABUS)features combined with Ki-67 in predicting pathological complete response(pCR)after neoadjuvant chemotherapy(NAC)in triple-negative breast cancer(TNBC).Methods A retrospective analysis was conducted on 127 female TNBC patients treated at Xijing Hospital,Air Force Medical University from March 2019 to December 2023.All patients underwent NAC and surgical treatment after ABUS examination.Based on postoperative pathological results,patients were divided into pCR group(n=60)and non-pathological complete response(npCR)group(n=67).Differences in various parameters before NAC were compared between the two groups.LASSO regression was used to identify independent factors influencing pCR after NAC in TNBC patients,and a predictive model was constructed using multivariate logistic regression.The prediction model was internally validated using the Bootstrap method(1000 resamples).The discriminative ability of the model was evaluated using receiver operating characteristic(ROC)curves,and the area under the curves(AUCs)of different prediction models were compared using De-long's test.The accuracy of the model was assessed using calibration curves,and the clinical benefit of the model was evaluated using clinical decision curve analysis(DCA).Results Significant differences were observed between two groups in terms of age,Ki-67,menopausal status,tumor type,posterior echo,coronal plane convergence sign,coronal plane skip sign,and coronal plane white wall sign before NAC(P<0.05).LASSO regression analysis showed that Ki-67,coronal plane convergence sign,and coronal plane white wall sign were independent influencing factors of pCR after NAC in TNBC patients(P<0.05).The AUC of the multivariate logistic regression model based on Ki-67 was 0.733(95%CI 0.646-0.819),the AUC of ABUS model was 0.777(95%CI 0.695-0.858),and the AUC of ABUS combined with Ki-67 model was 0.816(95%CI 0.741-0.890).De-long's test showed that the AUC of the combined model was higher than those of ABUS feature model and Ki-67 model,with statistically significant differences(P<0.05).There was no significant difference in the AUC between ABUS feature model and Ki-67 model(P=0.40).Hosmer-Lemeshow test indicated that the combined model had a good fit(P=0.304).Internal validation results showed that the combined model had a good stability with a consistency index(C-index)of 0.820(95%CI 0.726-0.879).The calibration curve demonstrated good consistency between the predicted and actual probabilities of the combined prediction model,and the DCA curve indicated that the model had favorable clinical benefit.Conclusion The combined ABUS feature and Ki-67 model can be used to predict the probability of pCR after NAC in TNBC patients,providing a reference for the formulation of clinical treatment plans in TNBC patients.

Objective To analyze the relationship between frailty and acute kidney injury(AKI)after hip fracture surgery in the elderly.Methods A total of 405 elderly patients who underwent hip fracture surgery in Jieyang People's Hospital from August 2021 to January 2023 were retrospectively analysed.According to the modified frailty index(mFI),they were divided into frail group(mFI≥0.27,n=112)and non-frail group(mFI<0.27,n=293).Postoperative AKI was defined according to the Kidney Disease:Improving Global Outcomes(KDIGO)criteria.After 1:1 propensity score matching(PSM),100 cases in each group were successfully matched.Univariable and multivariable logistic regression models,propensity score adjustment,PSM,inverse probability of treatment weighting(IPTW),standardized mortality ratio weighting(SMRW),pairwise algorithm(PA)weighting,and overlap weighting(OW)methods were used to analyze the relationship between frailty and postoperative AKI.Stratified analyses were performed according to age(≥80 or<80 years),gender,whether angiotensin-converting enzyme inhibitors(ACEI)/angiotensin Ⅱreceptor antagonists(ARB)were used,and whether intraoperative hypotension occurred.Results After PSM,there were no significant differences between the two groups in age,sex,surgical type,ACEI/ARB,blood urea nitrogen,serum creatinine,intraoperative blood loss,and intraoperative hypotension[standardized mean difference(SMD)<0.1].In both the original cohort and the matched cohort,the incidence of AKI was higher in frail group than in non-frail group(25.9%vs.8.9%,P<0.001;28.0%vs.11.0%,P=0.002).Analysis of the risk of postoperative AKI in elderly hip fracture patients in frail group found that compared with the non-frail group,in the univariate logistic regression model the odds ratio(OR)and a 95%confidence interval(CI)for the frail group was 3.59(2.00-6.43),P<0.001,and in the multivariable logistic regression model,the OR(95%CI)for frail group was 3.04(1.55-5.95),P=0.001.After adjustment for propensity score,the OR(95%CI)for frail group was 2.85(1.52-5.34),P=0.001,and the OR(95%CI)for frail group after PSM was 3.15(1.47-6.75),P=0.003.After IPTW,SMRW,PA weighting,and OW,the OR(95%CI)for frail group were 2.48(1.37-4.50),2.43(1.41-4.19),2.63(1.25-5.54),and 2.69(1.07-6.78),respectively,with P<0.05.The interaction tests were not statistically significant for age,sex,use of ACEI/ARB,and intraoperative hypotension(P>0.05).Conclusion In elderly patients with hip fractures,preoperative frailty may be a risk factor for postoperative AKI.