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 evaluate the short-and medium-term efficacy of posterior medial branch block in the treatment of persistent pain after percutaneous vertebral augmentation. METHODS: From January 2018 to January 2023, a total of 1, 062 patients with osteoporotic vertebral compression fractures underwent percutaneous vertebral augmentation. Among them, 32 elderly patients who experienced persistent low back pain after surgery and subsequently received posterior medial branch block and cryoablation were included. Six patients died during follow-up, leaving 26 patients for final analysis (1 male, 25 females). The mean age was (82.96±5.66) years (ranged, 76 to 94 years). The mean body mass index was (23.76±3.08) kg·m^-2(ranged 18.1 to 27.2 kg·m^-2). The bone mineral density T-value ranged from -2.5 to -4.3 with a mean of (-3.09±0.56). The mean volume of bone cement injected was 6.00 (5.38, 7.00) ml. Fracture locations were T₁₁ (2 cases), T₁₂ (7 cases), L₁ (10 cases), L₂ (6 cases), and L₃ (1 case). The mean interval from vertebral augmentation to block treatment was (7.12±2.22) months (rangd 6 to 12 months). The vertebral augmentation procedures were percutaneous kyphoplasty(PKP) in 12 cases and percutaneous vertebroplasty (PVP) in 14 cases. At the 2nd week, 3rd month, and 6th month after the block, the numerical rating scale(NRS), Oswestry disability index(ODI), patient satisfaction, and pain relief rate at the 6th month were evaluated. Relationships between pain relief rate at the 6th month after the last treatment and possible influencing factors were analyzed. RESULTS: Compared with X-ray films after percutaneous vertebral augmentation, the X-ray films before block showed an increase in kyphotic angle and vertebral compression rate, with statistically significant differences(P<0.05). At the 2nd week, 3rd month, and 6th month after posterior medial branch block and cryoablation, NRS and ODI scores were significantly lower than before the block(P<0.05). Among the 26 patients, 5 received additional cryoablation. At the 6th month after the last treatment, 19 patients reported excellent or good satisfaction. Univariate binary Logistic analysis showed all P>0.05, and no independent factor affecting final satisfaction or pain relief at 6 months after the last treatment was identified. CONCLUSION Posterior medial branch block(with cryoablation) can effectively improve short-and medium-term symptoms and function in patients with persistent axial low back pain after percutaneous vertebral augmentation for osteoporotic vertebral fractures.
Humans ; Male ; Female ; Aged ; Spinal Fractures/surgery* ; Aged, 80 and over ; Osteoporotic Fractures/surgery* ; Vertebroplasty/adverse effects* ; Nerve Block/methods*

Testicular histology based on testicular biopsy is an important factor for determining appropriate testicular sperm extraction surgery and predicting sperm retrieval outcomes in patients with azoospermia. Therefore, we developed a deep learning (DL) model to establish the associations between testicular grayscale ultrasound images and testicular histology. We retrospectively included two-dimensional testicular grayscale ultrasound from patients with azoospermia (353 men with 4357 images between July 2017 and December 2021 in The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China) to develop a DL model. We obtained testicular histology during conventional testicular sperm extraction. Our DL model was trained based on ultrasound images or fusion data (ultrasound images fused with the corresponding testicular volume) to distinguish spermatozoa presence in pathology (SPP) and spermatozoa absence in pathology (SAP) and to classify maturation arrest (MA) and Sertoli cell-only syndrome (SCOS) in patients with SAP. Areas under the receiver operating characteristic curve (AUCs), accuracy, sensitivity, and specificity were used to analyze model performance. DL based on images achieved an AUC of 0.922 (95% confidence interval [CI]: 0.908-0.935), a sensitivity of 80.9%, a specificity of 84.6%, and an accuracy of 83.5% in predicting SPP (including normal spermatogenesis and hypospermatogenesis) and SAP (including MA and SCOS). In the identification of SCOS and MA, DL on fusion data yielded better diagnostic performance with an AUC of 0.979 (95% CI: 0.969-0.989), a sensitivity of 89.7%, a specificity of 97.1%, and an accuracy of 92.1%. Our study provides a noninvasive method to predict testicular histology for patients with azoospermia, which would avoid unnecessary testicular biopsy.
Humans ; Male ; Azoospermia/diagnostic imaging* ; Deep Learning ; Testis/pathology* ; Retrospective Studies ; Adult ; Ultrasonography/methods* ; Sperm Retrieval ; Sertoli Cell-Only Syndrome/diagnostic imaging*

Traditional Chinese medicine(TCM) decoction pieces are a core carrier for the inheritance and innovation of TCM, and their quality and safety are critical to public health and the sustainable development of the industry. Conventional quality control models, while having established a well-developed system through long-term practice, still face challenges such as relatively long inspection cycles, insufficient objectivity in characterizing complex traits, and urgent needs for improving the efficiency of integrating multidimensional quality information when confronted with the dual demands of large-scale production and precision quality control. With the rapid development of artificial intelligence, machine learning can deeply analyze multidimensional data of the morphology, spectroscopy, and chemical fingerprints of decoction pieces by constructing high-dimensional feature space analysis models, significantly improving the standardization level and decision-making efficiency of quality evaluation. This article reviews the research progress in the application of machine learning in the processing, production, and rapid quality evaluation of TCM decoction pieces. It further analyzes current challenges in technological implementation and proposes potential solutions, offering theoretical and technical references to advance the digital and intelligent transformation of the industry.
Machine Learning ; Drugs, Chinese Herbal/standards* ; Quality Control ; Medicine, Chinese Traditional/standards* ; Humans

Aim To study the protective effect of the silibinin derivative Sil-1 on acute myocardial ischemia in SD rats and its mechanism of action.Methods Af-ter 18 hours of oxygen-glucose deprivation and treat-ment of H9c2 cells,the protective effect of Sil-1 on rat cardiomyocytes was examined.SD rats were treated 30 minutes before surgery,followed by 24 h ligation of the left anterior descending coronary artery.The cardiopro-tective effects of Sil-1 and its mechanisms for improving myocardial ischemic injury were investigated using pro-teomics technology.Results In vitro,compared with the control group,the activity of H9c2 cells in the mod-el group showed reduced cell viability,increased dead cells,elevated ROS and higher levels of LDH and in-flammatory cytokines TNF-α,IL-1β and IL-6 in the culture medium.Sil-1 could improve the above condi-tions to different degrees.In vivo,compared with the control group,rats in the model group showed signifi-cantly higher T waves on electrocardiogram,significant ischemic areas in the heart section,disorganized ar-rangement of cardiomyocytes,increased inflammatory factor infiltration and elevated CK,CK-MB,LDH and inflammatory factors TNF-α,IL-6 and IL-1β.Besides,NF-κB phosphorylation levels in myocardial tissue in-creased.Sil-1 improved the above conditions to varying degrees.The results of proteomics showed that 90 pro-teins were found between the control vs model group and the Sil-1 vs model group,and KEGG enrichment a-nalysis showed that MAPK,chemokines,VEGF and other signaling pathways were abundant.Western blot results showed that Sil-1 blocked the phosphorylation of ERK,JNK and p38 MAPK.Conclusions Sil-1 inhib-its the MAPK pathway by blocking the phosphorylation of JNK,ERK,and p38 MAPK,and achieves a protec-tive effect on rats with acute myocardial infarction.

Aim To study the protective effect of a combination of IDO-1 inhibitor(3-047)with Icartin(Y003)at a mass ratio of 1∶1.6 on diabetic nephrop-athy in db/db mice and its mechanism of action.Methods After 24 weeks of treatment in db/db mice,on the basis of pharmacodynamic evaluation,16S rD-NA gene sequencing combined with untargeted metabo-lomics was used to further investigate the mechanism of improvement of diabetic nephropathy from the perspec-tive of the"microbial-intestinal-nephrotic"axis by the combination of 3-047 and Y003.Results Compared with the control group,mice in the model group showed significantly higher levels of FBG,Scr,BUN,TC,TG,LDL-C,lower levels of HDL-C(P＜0.05),significantly increased urinary albumin excretion rate,thickening of the glomerular basement membrane and dilatation of the tunica albuginea,aggravation of oxida-tive stress damage,lower abundance,structural and functional disorders of the intestinal flora.The combi-nation of 3-047 and Y003 could improve the above conditions to different degrees,significantly increase the relative abundance of Alloprevotella,Alistipes and Dubosiella,and decrease the relative abundance of Ligilactobacillus,Dubosiella and Lactococcus.A total of 11 biomarkers with significant differences were screened by metabolomics and enriched to the pathways of alanine,tyrosine and tryptophan biosynthesis,and unsaturated fatty acid biosynthesis.Conclusions The combination of 3-047 and Y003 could improve the dis-orders of glucose-lipid metabolism,reduce the structur-al and functional damage of renal tissues,and alleviate oxidative stress by regulating the intestinal flora and re-lated amino acid metabolism,and thus achieve a pro-tective effect on mice with diabetic nephropathy,dem-onstrating that the intestinal flora and the related me-tabolites are potential targets for the treatment of dia-betic nephropathy.

Aim To study the protective effect of the silibinin derivative Sil-1 on acute myocardial ischemia in SD rats and its mechanism of action.Methods Af-ter 18 hours of oxygen-glucose deprivation and treat-ment of H9c2 cells,the protective effect of Sil-1 on rat cardiomyocytes was examined.SD rats were treated 30 minutes before surgery,followed by 24 h ligation of the left anterior descending coronary artery.The cardiopro-tective effects of Sil-1 and its mechanisms for improving myocardial ischemic injury were investigated using pro-teomics technology.Results In vitro,compared with the control group,the activity of H9c2 cells in the mod-el group showed reduced cell viability,increased dead cells,elevated ROS and higher levels of LDH and in-flammatory cytokines TNF-α,IL-1β and IL-6 in the culture medium.Sil-1 could improve the above condi-tions to different degrees.In vivo,compared with the control group,rats in the model group showed signifi-cantly higher T waves on electrocardiogram,significant ischemic areas in the heart section,disorganized ar-rangement of cardiomyocytes,increased inflammatory factor infiltration and elevated CK,CK-MB,LDH and inflammatory factors TNF-α,IL-6 and IL-1β.Besides,NF-κB phosphorylation levels in myocardial tissue in-creased.Sil-1 improved the above conditions to varying degrees.The results of proteomics showed that 90 pro-teins were found between the control vs model group and the Sil-1 vs model group,and KEGG enrichment a-nalysis showed that MAPK,chemokines,VEGF and other signaling pathways were abundant.Western blot results showed that Sil-1 blocked the phosphorylation of ERK,JNK and p38 MAPK.Conclusions Sil-1 inhib-its the MAPK pathway by blocking the phosphorylation of JNK,ERK,and p38 MAPK,and achieves a protec-tive effect on rats with acute myocardial infarction.

Aim To study the protective effect of a combination of IDO-1 inhibitor(3-047)with Icartin(Y003)at a mass ratio of 1∶1.6 on diabetic nephrop-athy in db/db mice and its mechanism of action.Methods After 24 weeks of treatment in db/db mice,on the basis of pharmacodynamic evaluation,16S rD-NA gene sequencing combined with untargeted metabo-lomics was used to further investigate the mechanism of improvement of diabetic nephropathy from the perspec-tive of the"microbial-intestinal-nephrotic"axis by the combination of 3-047 and Y003.Results Compared with the control group,mice in the model group showed significantly higher levels of FBG,Scr,BUN,TC,TG,LDL-C,lower levels of HDL-C(P＜0.05),significantly increased urinary albumin excretion rate,thickening of the glomerular basement membrane and dilatation of the tunica albuginea,aggravation of oxida-tive stress damage,lower abundance,structural and functional disorders of the intestinal flora.The combi-nation of 3-047 and Y003 could improve the above conditions to different degrees,significantly increase the relative abundance of Alloprevotella,Alistipes and Dubosiella,and decrease the relative abundance of Ligilactobacillus,Dubosiella and Lactococcus.A total of 11 biomarkers with significant differences were screened by metabolomics and enriched to the pathways of alanine,tyrosine and tryptophan biosynthesis,and unsaturated fatty acid biosynthesis.Conclusions The combination of 3-047 and Y003 could improve the dis-orders of glucose-lipid metabolism,reduce the structur-al and functional damage of renal tissues,and alleviate oxidative stress by regulating the intestinal flora and re-lated amino acid metabolism,and thus achieve a pro-tective effect on mice with diabetic nephropathy,dem-onstrating that the intestinal flora and the related me-tabolites are potential targets for the treatment of dia-betic nephropathy.

Objective Studies on the relationship between iodine,vitamin A(VA),and vitamin D(VD)and thyroid function are limited.This study aimed to analyze iodine and thyroid-stimulating hormone(TSH)status and their possible relationships with VA,VD,and other factors in postpartum women. Methods A total of 1,311 mothers(896 lactating and 415 non-lactating)from Hebei,Zhejiang,and Guangxi provinces were included in this study.The urinary iodine concentration(UIC),TSH,VA,and VD were measured. Results The median UIC of total and lactating participants were 142.00 μg/L and 139.95 μg/L,respectively.The median TSH,VA,and VD levels in all the participants were 1.89 mIU/L,0.44 μg/mL,and 24.04 ng/mL,respectively.No differences in the UIC were found between lactating and non-lactating mothers.UIC and TSH levels were significantly different among the three provinces.The rural UIC was higher than the urban UIC.Obese mothers had a higher UIC and a higher prevalence of excessive TSH.Higher UICs and TSHs levels were observed in both the VD deficiency and insufficiency groups than in the VD-sufficient group.After adjustment,no linear correlation was observed between UIC and VA/VD.No interaction was found between vitamins A/D and UIC on TSH levels. Conclusion The mothers in the present study had no iodine deficiency.Region,area type,BMI,and VD may be related to the iodine status or TSH levels.

Abstract: Objective　To investigate the clinical and laboratory characteristics of pulmonary infection caused by Nocardia otitidiscaviarum. Methods　The clinical data of a patient with pulmonary infection caused by Nocardia otitidiscaviarum were reported, and the clinical characteristics, laboratory characteristics and drug sensitivity of pulmonary infection caused by Nocardia otitidiscaviarum were summarized in combination with the relevant literature at home and abroad from January 2010 to December 2022. Results　A 67-year-old female patient was admitted to the hospital on June 30, 2020 because of "repeated chest tightness and shortness of breath for 3 years, aggravated cough, expectoration and fever". The sputum, alveolar lavage fluid and blood of the patient were collected for culture, and the detected pathogenic bacteria were identified. There are pathogenic bacteria growing in sputum and alveolar lavage fluid, which are identified as Nocardia otitidiscaviarum by Autof ms mass spectrometer. According to the results of pathogenic bacteria and the patient's condition, meropenem combined with compound sulfamethoxazole tablets were given anti-infection treatment, and the patient's condition improved and discharged. Conclusion　The clinical manifestations and imaging features of nocardiosis are lack of specificity, and are prone to misdiagnosis and missed diagnosis. Etiology is the key to disease diagnosis, and clinical examination and culture should be conducted in time.