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.

Shengjiangsan is a classic formula for treating warm diseases with wide clinical application and accurate efficacy. There are different opinions on the origin of this formula and lacks key information research on this formula. Therefore， in this study， we conducted systematic research into the historic origin， composition， and other key information of this Shengjiangsan. Results showed that Shengjiangsan has different versions， with "Neixian Fufang"， "Jiawei Jianghuangwan"， "Peizhensan"， and "Taijiwan" being the same formula with different names. Shengjiangsan was first recorded as "Neixian Fufang" in Wanbing Huichun written by GONG Tingxian from the Ming dynasty， inherited and developed by YANG Lishan from Qing dynasty， and has been passed down to modern times. Pills and powder are two main forms of Shengjiangsan， and powder has become more popular nowadays. According to the measurement system of Ming and Qing dynasties， the recommended dosage and usage of Shengjiangsan are as follows. For the pill version of Shengjiangsan， Bombyx Batryticatus of 74.6 g， Curcumae Longae Rhizoma of 9.325 g， Cicadae Periostracum of 9.325 g， and Rhei Radix et Rhizoma of 149.2 g were processed into pills for preparation. Single dosage is Bombyx Batryticatus of 1.15 g， Curcumae Longae Rhizoma of 0.14 g， Cicadae Periostracum of 0.14 g， and Rhei Radix et Rhizoma of 2.3 g， with halved dosage applied for children. For the powder version of Shengjiangsan， the dosage varied in accordance with the severity of the disease. Bombyx Batryticatus of 1.84 g， Curcumae Longae Rhizoma of 0.28 g， Cicadae Periostracum of 0.92 g， and Rhei Radix et Rhizoma of 3.68 g were processed into powder for patients with mild symptoms. Bombyx Batryticatus of 2.48 g， Curcumae Longae Rhizoma of 0.37 g， Cicadae Periostracum of 1.23 g， and Rhei Radix et Rhizoma of 4.91 g were processed into powder for patients with severe symptoms. Bombyx Batryticatus of 3.68 g， Curcumae Longae Rhizoma of 1.84 g， Cicadae Periostracum of 0.55 g， and Rhei Radix et Rhizoma of 7.36 g were processed into powder for patients with critical conditions. In this formula， four herbs were ground to fine powder. For patients with mild symptoms， the whole formula was divided into four dosages， and each dosage weighed 6.71 g. The 200 mL yellow rice wine and 18.65 g honey were added， and the solution was stirred and taken cold till full recovery. For patients with severe symptoms， the whole formula was divided into three dosages， and each weighed 8.95 g. 300 mL yellow rice wine and 27.98 g honey were added， and the solution was stirred and taken cold. For patients with critical conditions， the whole formula was divided into two dosages， and each weighed 13.43 g. 400 mL yellow rice wine and 37.3 g honey were added， and the solution was stirred and taken cold. Shengjiangsan has the effect of ascending lucidity and descending turbidity， dissipating wind， and clearing heat. It is specialized in treating severe heat in exterior， interior， and triple energizers in warm diseases and has a wide modern clinical application. In this study， the historic evolution and key information of Shengjiangsan were reviewed and analyzed， and the key information table of Shengjiangsan was attached， serving as a reference for scholars' research and a theoretical basis for its market transformation.

Congenital heart disease (CHD) is a congenital malformation resulting from abnormal embryonic development of the heart and great vessels, accounting for approximately 25% of all congenital malformations. Children with CHD are often complicated by short stature. Although surgical treatment can improve their growth and development to a certain extent, some children still experience growth retardation after surgery. Recombinant human growth hormone (rhGH) is the main drug for treating short stature, but its efficacy and safety in the treatment of patients with concomitant CHD warrant further investigation. This article reports six cases of children with CHD and short stature who were treated with rhGH. Through a literature review, we summarize and discuss the therapeutic efficacy, follow-up experiences, and adverse reactions of rhGH treatment, aiming to provide references for clinicians in applying rhGH to treat patients with CHD and short stature.

Background and Objectives: There is no dedicated occlusive device for closing coronary artery fistulas (CAFs), and specific efficacy and safety data of various off-label occlusive devices for CAFs closure are scarce. Methods: Patients undergoing transcatheter closure of CAFs from January 2011 to December 2022 were included in the single-center retrospective study. The study population was divided into 2 groups: coils group (n=35) and patent ductus arteriosus (PDA) occluders group (n=66). Results: No significant intergroup differences were observed in demographic characteristics except age. The presence of multiple CAF origins (54.3% vs. 4.5%, p<0.001) and multiple draining sites (51.4% vs. 3.0%, p<0.001) were more common in the coils group. In contrast, the presence of aneurysm (72.7% vs. 14.3%, p<0.001), and large fistula (75.8% vs. 37.1%, p<0.001) were more prevalent in the PDA occluders group. The acute procedural success rate of the PDA occluders group was higher compared to that of the coils group (87.9% vs.62.9%, adjusted odds ratio [OR], 7.20; 95% confidence interval, 1.59–32.64; p=0.01).In addition, no significant intergroup differences were noted in both the recanalization rate (7.8% vs. 20%, p=0.107) and the reintervention rate (3.1% vs. 8.6%, p=0.342). Conclusions Transcatheter closure of CAFs using PDA occluders was associated with significantly higher acute procedural success rates compared to coil embolization with comparable late outcomes.

Pancreatic cancers (PCs) is a common malignant tumor with poor prognosis in the digestive system. Its main treatment methods include surgery, radiotherapy, chemotherapy, and targeted therapy. The early diagnosis rate of hidden onset of PCs is low, and most patients have already lost the opportunity to undergo surgery when diagnosed with PCs. Chemotherapy is still the main treatment for advanced PCs, but the use of chemotherapy drugs in PCs can easily lead to drug resistance. The most significant feature that distinguishes PCs from other tumors is its rich and dense matrix, which not only hinders drug penetration but also impedes the infiltration of immune cells. The above reasons have led to a very low survival rate of PCs patients. Therefore, drug delivery systems are very important in the diagnosis and treatment of PCs. They can improve drug delivery, enhance biological barrier penetration, reduce side effects, and combine multiple treatment methods. Therefore, the treatment prospects of PCs are very broad. Currently, drug delivery systems widely applied in PCs primarily include nanodrug delivery systems, tumor microenvironment-targeted drug delivery system, immunotherapy drug delivery system, gene therapy drug delivery system, and combination therapy drug delivery system that synergize multiple therapeutic modalities. Emerging drug delivery systems (DDSs) have revolutionized PCs treatment by addressing these challenges through multiple mechanisms. Nanoformulations improve drug solubility, prolong circulation time, and reduce systemic toxicity via passive/active targeting. Smart DDSs responsive to PCs-specific stimuli enable extracellular matrix degradation, tumor-associated fibroblasts reprogramming, and vascular normalization to enhance drug accessibility. Last but not least, carrier systems loaded with myeloid-derived suppressor cell inhibitors or T cell activators can reverse immunosuppression and potentiate immunotherapy efficacy. Advanced platforms co-deliver chemotherapeutics with immunomodulators, gene-editing tools, or sonodynamic agents to achieve synergistic antitumor effects. These platforms aim to address critical challenges in PCs treatment, such as enhancing drug bioavailability, overcoming stromal barriers, reprogramming immunosuppressive niches, and achieving multi-mechanistic antitumor effects. This article provides a systematic summary and prospective analysis of the current development status, latest cutting-edge advances, opportunities, and challenges of the above-mentioned drug delivery systems in the field of PCs therapy.

Background and Objectives: There is no dedicated occlusive device for closing coronary artery fistulas (CAFs), and specific efficacy and safety data of various off-label occlusive devices for CAFs closure are scarce. Methods: Patients undergoing transcatheter closure of CAFs from January 2011 to December 2022 were included in the single-center retrospective study. The study population was divided into 2 groups: coils group (n=35) and patent ductus arteriosus (PDA) occluders group (n=66). Results: No significant intergroup differences were observed in demographic characteristics except age. The presence of multiple CAF origins (54.3% vs. 4.5%, p<0.001) and multiple draining sites (51.4% vs. 3.0%, p<0.001) were more common in the coils group. In contrast, the presence of aneurysm (72.7% vs. 14.3%, p<0.001), and large fistula (75.8% vs. 37.1%, p<0.001) were more prevalent in the PDA occluders group. The acute procedural success rate of the PDA occluders group was higher compared to that of the coils group (87.9% vs.62.9%, adjusted odds ratio [OR], 7.20; 95% confidence interval, 1.59–32.64; p=0.01).In addition, no significant intergroup differences were noted in both the recanalization rate (7.8% vs. 20%, p=0.107) and the reintervention rate (3.1% vs. 8.6%, p=0.342). Conclusions Transcatheter closure of CAFs using PDA occluders was associated with significantly higher acute procedural success rates compared to coil embolization with comparable late outcomes.

Acute kidney injury (AKI) is a common clinically critical syndrome in hospitalized patients with high morbidity and mortality. At present, the mechanism of AKI has not been fully elucidated, and no therapeutic drugs exist. As known, glycolytic product lactate is a key metabolite in physiological and pathological processes. The kidney is an important gluconeogenic organ, where lactate is the primary substrate of renal gluconeogenesis in physiological conditions. During AKI, altered glycolysis and gluconeogenesis in kidneys significantly disturb the lactate metabolic balance, which exert impacts on the severity and prognosis of AKI. Additionally, lactate-derived posttranslational modification, namely lactylation, is novel to AKI as it could regulate gene transcription of metabolic enzymes involved in glycolysis or Warburg effect. Protein lactylation widely exists in human tissues and may severely affect non-histone functions. Moreover, the strategies of intervening lactate metabolic pathways are expected to bring a new dawn for the treatment of AKI. This review focused on renal lactate metabolism, especially in proximal renal tubules after AKI, and updated recent advances of lactylation modification, which may help to explore potential therapeutic targets against AKI.
Humans ; Acute Kidney Injury/metabolism* ; Lactic Acid/metabolism* ; Animals ; Glycolysis/physiology* ; Gluconeogenesis/physiology* ; Kidney/metabolism*

Background and Objectives: There is no dedicated occlusive device for closing coronary artery fistulas (CAFs), and specific efficacy and safety data of various off-label occlusive devices for CAFs closure are scarce. Methods: Patients undergoing transcatheter closure of CAFs from January 2011 to December 2022 were included in the single-center retrospective study. The study population was divided into 2 groups: coils group (n=35) and patent ductus arteriosus (PDA) occluders group (n=66). Results: No significant intergroup differences were observed in demographic characteristics except age. The presence of multiple CAF origins (54.3% vs. 4.5%, p<0.001) and multiple draining sites (51.4% vs. 3.0%, p<0.001) were more common in the coils group. In contrast, the presence of aneurysm (72.7% vs. 14.3%, p<0.001), and large fistula (75.8% vs. 37.1%, p<0.001) were more prevalent in the PDA occluders group. The acute procedural success rate of the PDA occluders group was higher compared to that of the coils group (87.9% vs.62.9%, adjusted odds ratio [OR], 7.20; 95% confidence interval, 1.59–32.64; p=0.01).In addition, no significant intergroup differences were noted in both the recanalization rate (7.8% vs. 20%, p=0.107) and the reintervention rate (3.1% vs. 8.6%, p=0.342). Conclusions Transcatheter closure of CAFs using PDA occluders was associated with significantly higher acute procedural success rates compared to coil embolization with comparable late outcomes.

Background and Objectives: There is no dedicated occlusive device for closing coronary artery fistulas (CAFs), and specific efficacy and safety data of various off-label occlusive devices for CAFs closure are scarce. Methods: Patients undergoing transcatheter closure of CAFs from January 2011 to December 2022 were included in the single-center retrospective study. The study population was divided into 2 groups: coils group (n=35) and patent ductus arteriosus (PDA) occluders group (n=66). Results: No significant intergroup differences were observed in demographic characteristics except age. The presence of multiple CAF origins (54.3% vs. 4.5%, p<0.001) and multiple draining sites (51.4% vs. 3.0%, p<0.001) were more common in the coils group. In contrast, the presence of aneurysm (72.7% vs. 14.3%, p<0.001), and large fistula (75.8% vs. 37.1%, p<0.001) were more prevalent in the PDA occluders group. The acute procedural success rate of the PDA occluders group was higher compared to that of the coils group (87.9% vs.62.9%, adjusted odds ratio [OR], 7.20; 95% confidence interval, 1.59–32.64; p=0.01).In addition, no significant intergroup differences were noted in both the recanalization rate (7.8% vs. 20%, p=0.107) and the reintervention rate (3.1% vs. 8.6%, p=0.342). Conclusions Transcatheter closure of CAFs using PDA occluders was associated with significantly higher acute procedural success rates compared to coil embolization with comparable late outcomes.

ObjectiveTo analyze the characteristics and influencing factors of elderly hospitalized patients with carbapenem-resistant gram-negative bacillus (CRO) infection in the intensive care unit (ICU) of a gradeⅡ level A general hospital in Yangpu District of Shanghai, and to provide scientific basis for the prevention and control of hospital-acquired CRO infection in such hospitals. MethodsThe clinical data of elderly ICU patients (age ≥60 years) from January 2019 to December 2023 were retrospectively collected. A total of 122 cases with hospital-acquired CRO infection were used as the case group, and a total of 68 cases with carbapenem-sensitive gram-negative (CSO) infection were used as the control group. The clinical characteristics of the two groups were analyzed, and univariate analysis and logistic regression analysis were performed for screening for possible influencing factors on hospital-acquired CRO infection. ResultsThe main pathogens of CRO infection were carbapenem-resistant Acinetobacter baumannii (CRAB) (53 cases, 43.44%) and carbapenem-resistant Klebsiella pneumoniae (CRKP) (46 cases, 37.70%), and 17 patients (13.93%) had more than two types of CRO infection. Among the CRO infection, the main sites were lower respiratory tract infection (58 cases, 47.54%), ventilator-associated pneumonia (21 cases, 17.21%), and catheter-associated urinary tract infections (16 cases, 13.11%). The incidence rate of poor prognosis was higher in the CRO infection group (54.10%) than that in the CSO infection group (36.76%) (P=0.021). The results of univariate analysis showed that male, history of hospitalization within three months, chronic respiratory disease, hypoproteinemia, anemia, and history of invasive procedures prior to infection, including indwelling central venous catheter, invasive mechanical ventilation, urinary catheter, gastric tube placement and parenteral nutrition, in addition, heparin anticoagulation, the use of broad-spectrum penicillin, third-generation cephalosporins, fluoroquinolones, carbapenems, carbapenems combined with fluoroquinolones, carbapenems combined with glycopeptides, use of ≥3 antibiotics and long time of antibiotic use prior to infection were all associated with the CRO infection (P<0.05). The results of logistic regression analysis showed that use of carbapenems (OR=7.739, 95%CI: 2.226‒26.911), ≥3 types of antibiotics (OR=6.307, 95%CI: 1.674‒23.754), invasive mechanical ventilation (OR=4.082, 95%CI: 1.795‒9.281), urinary catheter (OR=3.554, 95%CI: 1.074‒11.758), and comorbid hypoproteinemia (OR=4.741, 95%CI: 2.039‒11.022) and diabetes (OR=3.245, 95%CI: 1.344‒7.839) were positively correlated with the risk of CRO infection. ConclusionConcurrent use of carbapenems with multiple other antibiotics, as well as the use of invasive mechanical ventilation, urinary catheter, and comorbid hypoproteinemia and diabetes, may be associated with an increased influencing of CRO infection. More attention should be paid to the prevention and control of infection in elderly patients with the above-mentioned risk factors, and active screening of drug-resistant bacteria should be strengthened. Besides, the rational use of broad-spectrum antibiotics such as carbapenems, avoiding unnecessary invasive operations, and paying attention to patient nutrition and blood glucose control all can reduce the incidence of CRO infection and help to improve clinical outcomes.