With the widespread use of antibiotics, drug-resistant bacterial infections have become a significant threat to human health. Finding new antibacterial strategies that can effectively control drug-resistant bacterial infections has become an urgent task. Unlike small molecule drugs that target bacterial proteins, antisense oligonucleotide (ASO) can target genes related to bacterial resistance, pathogenesis, growth, reproduction and biofilm formation. By regulating the expression of these genes, ASO can inhibit or kill bacteria, providing a novel approach for the development of antibacterial drugs. To overcome the challenge of delivering antisense oligonucleotide into bacterial cells, various drug delivery systems have been applied in this field, including cell-penetrating peptides, lipid nanoparticles and inorganic nanoparticles, which have injected new momentum into the development of antisense oligonucleotide in the antibacterial realm. This review summarizes the current development of small nucleic acid drugs, the antibacterial mechanisms, targets, sequences and delivery vectors of antisense oligonucleotide, providing a reference for the research and development of antisense oligonucleotide in the treatment of bacterial infections.

Objective:To understand the coverage and information consistency rate of National Immunization Program (NIP) vaccines among children born during 2020-2021 in Zhejiang Province, Chongqing City, and Shanxi Province (3 provinces) of China .Methods:A simple random sampling method was used to randomly select 3 counties (districts) from each of the 3 provinces, 5 townships from each county (district), and 5 villages from each township. Vaccination information for seven NIP vaccines was collected for children born between 2020 and 2021 in each village. The vaccination coverage, timely coverage, and consistency rates between the survey data and the Immunization Planning Information System data were analyzed.Results:A total of 1 117 children were investigated. The vaccination coverage for each dose of NIP vaccine ranged from 99.10% to 100.00%, with those in Zhejiang Province, Chongqing City, and Shanxi Province ranging from 99.19% to 100.00%, 98.92% to 100.00%, and 99.20% to 100.00%, respectively. The timely coverage of each dose of NIP vaccine ranged from 89.79% to 99.82%, with those in Zhejiang Province, Chongqing City, and Shanxi Province ranging from 94.09% to 99.73%, 89.52% to 99.73%, and 78.55% to 100.00%, respectively. The consistency rate of information on each dose of NIP vaccine ranged from 94.36% to 99.91%, with those in Zhejiang Province, Chongqing City, and Shanxi Province ranging from 97.85% to 99.73%, 98.92% to 100.00%, and 86.06% to 100.00%, respectively.Conclusions:Coverage of NIP vaccines was generally high among children born during 2020-2021 in the 3 provinces of China, but there were regional differences in the timely coverage of some vaccine doses and the vaccination information consistency rate. It is necessary to strengthen the timely vaccination of children's vaccine booster doses and optimize the management of vaccination services.

Objective:To evaluate the safety and effectiveness of fuzuloparib for the treatment of ovarian epithelial cancer patients in the real world setting.Methods:A retrospective analysis was conducted on the baseline data of 4 620 ovarian cancer patients who had received fuzuloparib monotherapy or combination therapy. Another 224 ovarian cancer patients who were willing to receive fuzuloparib monotherapy or combination therapy were prospectively enrolled, and their baseline characteristics, drug effectiveness, and safety data were analyzed.Results:(1) Among the 4 620 patients in the retrospective cohort, the median age of patients was 60 years; tumor types: 89.8% (4 149/4 620) had ovarian cancer. Among patients with clearly documented information, the vast majority had a histological type of serous carcinoma (82.9%, 3 770/4 546) and International Federation of Gynecology and Obstetrics (FIGO) staging of Ⅲ-Ⅳ (90.9%, 1 537/1 691). (2) Among the 224 patients in the prospective cohort, the median age of patients was 57 years; tumor types: 83.9% (188/224) had ovarian cancer. Among patients with clearly documented records, the predominant pathologic type was serous carcinoma (91.9%, 193/210), and FIGO stage was Ⅲ-Ⅳ in 79.9% (139/174). (3) Among the 224 prospective patients: 84 patients received first-line fluzoparib maintenance therapy, 92 patients received fluzoparib maintenance therapy after platinum-sensitive recurrence, 23 patients received direct fluzoparib treatment after platinum-sensitive recurrence, 19 patients received direct fluzoparib treatment after platinum-resistant recurrence. The median follow-up durations were 8.5, 8.7, 7.9, and 6.7 months, respectively. The median durations of fluzoparib treatment were 6.7, 4.8, 3.1, and 1.9 months, respectively. The median progression-free survival (PFS) times were not reached during follow-up, 12.6 months, not reached during follow-up, and 4.8 months, respectively. The 1-year PFS rates were 84.1%, 55.0%, 69.8%, and 45.5%, respectively. The remaining 6 patients received other fluzoparib regimens. (4) Among the 224 patients in the prospective dataset, 205 had safety data recorded. Of these, 127 patients (62.0%, 127/205) experienced treatment-related adverse events, with common events including anemia (24.4%, 50/205), thrombocytopenia (21.0%, 43/205), and leukopenia (19.5%, 40/205). Among the 205 patients, 43 (21.0%, 43/205) experienced grade 3 or higher treatment-related adverse events, with common events including anemia (8.3%, 17/205) and thrombocytopenia (8.3%, 17/205).Conclusions:The effectiveness of fuzuloparib in clinical application is generally consistent with other drugs in the same class, with good safety. This study provids new clinical evidence for the treatment of ovarian cancer with fuzuloparib.

Objective:To construct a decision tree model to predict the risk of breast cancer in patients with pathological nipple discharge.Methods:A total of 157 patients with pathological nipple discharge,who were diagnosed and treated at Weifang Municipal Hospital of Traditional Chinese Medicine from January 2019 to April 2024 and met the inclusion criteria,were selected.A risk prediction model for concurrent breast cancer in patients with pathological nipple discharge was developed using Logistic regression analysis.A decision tree was then constructed,and the predictive performance of the model was assessed based on the area under the receiver operating characteristic curve(AUC).Re-sults:The incidence of concurrent breast cancer among patients with pathological nipple discharge was 24.2%.Accord-ing to the results of binary Logistic regression analysis,elevated CEA and CA 153 levels in nipple discharge,as well as bloody discharge,emerged as independent risk factors for the development of breast cancer in such patients(P<0.05).Based on these findings,a decision tree model was constructed to predict the risk of concurrent breast cancer in patients with pathological nipple discharge.The validation results showed that the Logistic regression model had an AUC value of 0.800,while the decision tree model achieved an AUC value of 0.889.Conclusions:The decision tree model,built upon the identified influencing factors,exhibits strong predictive power for the risk of developing concurrent breast can-cer in patients with pathological nipple discharge,thus facilitating more precise preoperative diagnoses by clinicians for these patients.

BACKGROUND:Spinal cord injury often leads to neurogenic bladder with hyperreflexia of the forced urethral muscle,but there is a lack of clear understanding of its pathogenesis and treatment,and establishing a stable and reliable animal model has an important impact on revealing its pathomechanisms and exploring therapeutic approaches.OBJECTIVE:To investigate the effect of the number of times to urinate on neurogenic model rats after complete spinal cord transection in order to improve the postoperative survival and modeling rate of neurogenic model rats.METHODS:Out of 46 female Sprague-Dawley rats,6 were selected as the sham-operated group using the random number table method,and the remaining 40 rats were randomly divided into 0,1,3,and 5 times daily urination groups after complete spinal cord transection modeling,with 10 rats in each group.The residual urine volume was measured every 3 days within 19 postoperative days,and the survival and modeling were observed on the 19th day after the operation,and urodynamics tests and contraction experiments of isolated forced urethra muscle strips were performed.RESULTS AND CONCLUSION:(1)Survival and modeling rate:there was 10%survival rate and 10%modeling rate in the group of 0 times daily urination;20%survival rate and 10%modeling rate in the group of 1 time daily urination;70%survival rate and 70%modeling rate in the groups of 3 and 5 times daily urination.(2)Residual urine volume:compared with the sham-operated group,the residual urine volume of the groups of 3 and 5 times daily urination was significant increased on postoperative days 3,6,9,12,and 15(P<0.01);the residual urine volume of the groups of 3 and 5 times daily urination was increased on the 18th day after surgery(P<0.05).Compared with the 3 times daily urination group,the residual urine volume was decreased in the 5 times daily urination group on the 6th day after surgery(P<0.05),while there was no significant difference in the residual urine volume between the 3 and 5 times daily urination groups on the 3rd,9th,12th,15th,and 18th days after surgery.(3)Urodynamics:Compared with the sham-operated group,the differential pressure at the point of leakage was significantly reduced(P<0.01)and the maximal volume was significantly increased(P<0.01)in the 3 and 5 times daily urination groups.There was no statistical difference in the differential pressure at the point of leakage and the maximal volume between the 3 and 5 times daily urination groups.(4)Muscle-strip contraction test of isolated detrusor muscles:Compared with the sham-operated group,the contraction amplitude and frequency of detrusor muscle strips were significantly reduced in the 3 and 5 times daily urination groups(P<0.01).There was no statistically significant difference in the contraction amplitude and frequency of detrusor muscle strips between the 3 and 5 times daily-urination groups.In conclusion,assisted urination is one of the keys to establish a successful neurogenic model of urethral reflexes,and there is no significant difference in the effects of urinating 3 or 5 times a day on the neurogenic model.It is recommended to urinate at least 3 times a day based on the actual workload and the modeling rate.

Objective::This study aimed to investigate the feasibility, efficacy, and safety of using a miniature mobile integrated cabin-theatre equipped with angiography and surgical operating room capabilities, and to explore its therapeutic scope, effectiveness, and operational mode.Methods::A miniature mobile integrated operating cabin-theatre was deployed across 15 hospitals in 15 cities or counties in China from April 2012 to November 2024. The interventions and outcomes of interventional and minimally invasive surgical procedures were prospectively observed and evaluated; perioperative complications were documented, and the stability, adaptability, and mobility of the integrated system were assessed.Results::A total of 133 procedures were successfully performed, 130 of which were interventional and 3 minimally invasive. The angiography machine showed good imaging performance without any equipment failures, loosening, or damage, with normal chamber unfolding. One patient experienced a fever the day after laparoscopy, while none of the other patients exhibited perioperative complications such as infection, surgical site bleeding/hematoma, or reperfusion arrhythmia. The instrument was easily manipulated, aligning with the needs of clinical intervention and surgery, and was perceived by patients as being a comfortable environment, with no psychological or other obvious discomfort.Conclusions::The miniature mobile integrated cabin-theatre, comprising an angiography machine and an operating room, allows interventional or minimally invasive surgical procedures to be performed smoothly and safely. It can also provide rapid and efficient on-site treatment of acute and critical illnesses across multiple body systems, including the cardiovascular, cerebrovascular, and gastrointestinal systems.

Objective:To evaluate the clinical efficacy of transoral robotic surgery (TORS) in the treatment of malignant tongue base tumors.Methods:A multicenter study was conducted to collect and analyze the clinical data of patients with malignant tongue base tumors who underwent TORS at five otolaryngology-head and neck surgery centers in China, including Eye Ear Nose and Throat Hospital of Fudan University, Sun Yat-sen University Cancer Center, Tongji Hospital of Huazhong University of Science and Technology, Sun Yat-sen Memorial Hospital of Sun Yat-sen University, and the First Affiliated Hospital of China Medical University between January 2017 and January 2023. Among the patients, 38 were males and 11 were females, with a mean age of 59.0±8.8 years. Baseline characteristics, complications, and follow-up data were compared between groups. Independent sample t-tests or Mann-Whitney U tests was used for comparisons of continuous variables; chi-square tests or Fisher′s exact tests was applied for categorical variables. Survival analysis was performed using the Kaplan-Meier method to calculate overall survival and disease-free survival, and differences between groups were compared using the log-rank test. Results:Among the 49 patients, 41 (83.7%) were diagnosed with squamous cell carcinoma (SCC), with a p16 positive rate of 51.2% (21/41). There were no statistically significant differences between the p16-positive group ( n=21) and the p16-negative group ( n=20) in age, sex, or postoperative bleeding (all P>0.05). However, there was a significant difference in TNM stage between the two groups ( χ2=14.556, P=0.020), with the p16-positive group predominantly in stage I (66.7%) and the p16-negative group primarily in stages Ⅲ and Ⅳ (40.0% and 30.0%, respectively). The postoperative tracheotomy rate was 30.6% (15/49), and the incidence of postoperative bleeding was 6.1% (3/49). The 1-year and 3-year overall survival rates were 98.0% and 92.5%, respectively, while, the 1-year and 3-year disease-free survival rates were 89.2% and 84.9%, respectively. No significant differences were observed between the p16-positive and p16-negative groups in 3-year overall survival (100% vs. 83.8%, χ2=1.093, P=0.518) or 3-year disease-free survival (68.2% vs. 88.9%, χ2=2.161, P=0.382). Conclusion:TORS for malignant tongue base tumors demonstrates high clinical safety and favorable oncological outcomes.

Objective:To explore the clinical application value of transoral robotic surgery (TORS) in the treatment of tonsil squamous cell carcinoma (TSCC).Methods:A retrospective analysis was conducted. The clinical data of 157 TSCC patients were collected who received TORS at five medical centers, namely, the Sun Yat-sen University Cancer Center, Sun Yat-sen Memorial Hospital, Eye Ear Nose and Throat Hospital of Fudan University, the First Affiliated Hospital of China Medical University, and Tongji Hospital of Tongji Medical College, from January 1 2017 to July 31 2022. There were 130 males and 27 females, aged 24-85 years. All patients were followed-up at least for 2 years (2-year group), among them, 99 patients had a follow-up of 3 years (3-year group). The overall survival (OS), progression-free survival (PFS), clinical stage, human papillomavirus (HPV) infection status were analyzed. SPSS 25.0 and SAS 9.4 were used for statistical analysis.Results:The OS and PFS of the 2-year group were 91.7% and 87.9%, respectively. The OS and PFS of the 3-year group were 85.9% and 82.8%, respectively. The prognosis of patients with locally early-stage was better than that of locally advanced patients, with the OS of 94.4% for T1-2 vs. 78.0% for T3 ( P=0.005) and the PFS of 91.2% for T1-2 vs. 75.0% for T3 ( P=0.011) in the 2-year group; the OS of 91.1% for T1-2 vs. 65.0% for T3 ( P=0.004) and the PFS of 88.6% for T1-2 vs. 60.0% for T3 ( P=0.002) in the 3-year group; and also, the OS of 90.0% for stage Ⅰ-Ⅱ vs. 79.5% for stage Ⅲ-Ⅳ ( P=0.204) and the PFS of 86.7% for stage Ⅰ-Ⅱ vs. 76.9% for stage Ⅲ-Ⅳ ( P=0.188) in the 3-year group. The prognosis of HPV-positive TSCC patients was better than that of HPV-negative patients in the 3-year group, with the OS of 90.9% for HPV-positive vs. 80.5% for HPV-negative ( P=0.045) and the PFS of 90.9% for HPV-positive vs. 75.6% for HPV-negative ( P=0.047). The average time of postoperative tracheal cannula indwelling was 25.1 days. The indwelling rate and average indwelling time of the postoperative nasogastric tube were 94.3% (148/157) and 8.5 days, respectively. Conclusion:TORS has outstanding survival benefits for TSCC patients. HPV-positive TSCC patients have a better prognosis than HPV-negative patients. TORS treatment of TSCC patients has advantages in postoperative recovery and quality of life.

Objective:To investigate the efficacy and feasibility of transoral robotic surgery (TORS) for resection of tumors in the parapharyngeal spaces.Methods:The clinical data of 57 patients who underwent TORS for parapharyngeal space tumors from September 2018 to February 2024 were retrospectively analyzed. These patients were treated at five medical institutions: The First Affiliated Hospital of China Medical University, Eye & ENT Hospital of Fudan University, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, and Sun Yat-sen University Cancer Center. The patients were 28 males and 29 females, aged 17-77 years (median age, 47 years). The pathological types, locations, and sizes of the tumors, operation time, intraoperative bleeding volumes, postoperative hospital stays, and postoperative complications were evaluated. The data were analyzed using SPSS 27.0 software.Results:Postoperative pathological examination revealed 11 types of benign tumors. Among 57 cases, 27 cases had their tumors in the prestyloid spaces, predominantly with pleomorphic adenoma ( n=17), and 30 cases in the retrostyloid spaces, predominantly with schwannoma ( n=22). The tumor volumes ranged from 0.6 to 130.1 cm3, the intraoperative bleeding volumes ranged from 5 to 1 000 ml, the operation time ranged from 20 to 390 min, and the postoperative hospital stays ranged from 2 to 25 days. The total costs for individual cases were 36 000-100 000 yuan, with the highest cost in the case suffering from cerebrovascular accident. Four patients(7.0%) had tracheotomy and 36(63.2%) had nasogastric tube placement. Among the 57 patients, 5 had postoperative cavity effusion, 2 had wound dehiscence, 2 had cerebrovascular accidents, 1 had Horner syndrome, and 2 had other complications. The patients were followed up for 1-67 months, with only 1 patient with intracranial and extracranial communication relapsed. Conclusion:TORS is a safe and feasible approach for treating parapharyngeal space tumors, offering advantages such as minimal invasiveness, reduced blood loss, and faster recovery. It is suitable for parapharyngeal space tumors of various pathological types and locations. The postoperative complications are manageable, with favorable long-term follow-up results and low recurrence rates.

ObjectiveTo explore the characteristics of traditional Chinese medicine （TCM） syndromes in the patients with concurrent knee osteoarthritis （KOA） and postmenopausal osteoporosis （PMOP） and provide a scientific basis for precise TCM syndrome differentiation， diagnosis， and treatment of such concurrent diseases. MethodsA prospective， multicenter， cross-sectional clinical survey was conducted to analyze the characteristics of TCM syndromes in the patients with concurrent PMOP and KOA. Excel 2021 was used to statistically analyze the general characteristics of the included patients. Continuous variables were reported as x¯±s， and binary variables were reported as percentages. UCINET and Gephi were used to construct a complex "isease-syndrome-symptom" network for in-depth mining. Topological structure indicators， edge connection information between nodes， and weighted adjacency matrices were calculated by UCINET and Python. Gephi was used for complex network visualization. ResultsA total of 157 patients with concurrent PMOP and KOA from 12 TCM hospitals or community health service centers were selected for the collection of TCM syndrome and symptom information. A total of 4 main TCM syndromes were obtained， which were kidney-Yang deficiency （47.13%）， liver-kidney Yin deficiency （36.94%）， spleen-kidney Yang deficiency （8.92%）， and kidney Yin-Yang deficiency （7.01%）. In addition， 10 concurrent syndromes （mainly Qi stagnation and blood stasis， Qi and blood deficiency， spleen Yang deficiency， and cold-dampness） were identified. Based on the results of comprehensive frequency statistics and complex network analysis， as well as TCM theoretical knowledge and relevant guidelines， the general characteristics of concurrent PMOP and KOA and the main TCM syndromes in the dimensions of physical symptoms， pain， tongue and pulse manifestations， and defecation and urination were obtained. ConclusionThe main TCM syndromes in the patients with concurrent PMOP and KOA may be kidney Yang deficiency， liver-kidney Yin deficiency， spleen-kidney Yang deficiency， and kidney Yin-Yang deficiency， among which kidney Yang deficiency and liver-kidney Yin deficiency are the core TCM syndromes.