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 identify and analyze adverse drug event （ADE） signals associated with tirzepatide based on the FDA Adverse Event Reporting System （FAERS） database， providing a reference for clinical medication safety. METHODS ADE reports from January 1， 2022， to June 30， 2024， with tirzepatide as the primary suspected drug， were extracted from the FAERS database. Medical Dictionary for Regulatory Activities was used to systematically categorize the selected system organ class （SOC） and preferred term of ADE. Signal mining and analysis were performed using the reporting odds ratio method and the proportional reporting ratio method. RESULTS A total of 39 229 ADE reports related to tirzepatide were obtained， including 3 934 severe ADE reports （10.03%）. The majority of severe ADE reports were related to hospitalization or prolonged hospitalization （3.82%）， involving 131 positive ADE signals. Among the reports with documented patient gender and age， 26 195 were female （66.77%）， 7 869 were male （20.06%）， and the majority of patients were aged 18-64 years （54.26%）. The top three most frequently reported ADE were injection site pain， nausea， and injection site hemorrhage. Strong ADE signals not mentioned in the tirzepatide instruction included injection site coldness， starvation ketoacidosis， injection site hemorrhage， hunger， elevated adrenaline， injection site skin cracking， binge eating， skin laxity， intestinal sepsis， lack of satiety， and dysesthesia. Subgroup analysis for patient’s gender and age showed differences in the proportion of ADE reports across different SOC. Male patients or those aged≥65 years had a higher risk of gastrointestinal system disorders compared to female patients or those aged ＜65 years. CONCLUSIONS In clinical use of tirzepatide， in addition to monitoring ADE listed in the instruction， attention should also be paid to ADE not mentioned in the instruction， such as injection site coldness， starvation ketoacidosis， injection site hemorrhage， elevated adrenaline， and intestinal sepsis， to ensure patient safety.

OBJECTIVE To evaluate the efficacy， safety and cost-effectiveness of tirzepatide for diabetes mellitus type 2 （T2DM） and long-term weight management， and provide evidence-based basis for clinical drug treatment and health insurance policy formulation. METHODS Computer searches were conducted in Embase， PubMed， the Cochrane Library， CNKI and health technology assessment （HTA） official website from their inception to October 1st 2024 to collect HTA report， systematic review/ meta-analysis and pharmacoeconomic study on tirzepatide for the treatment of T2DM or for weight management. After data extraction and quality evaluation， descriptive analysis was performed on the research results. RESULTS Totally 18 papers were included， including 14 systematic reviews/meta-analyses and 4 pharmacoeconomics studies， and no HTA report was retrieved. In terms of efficacy， most results showed that the tirzepatide 10 mg and 15 mg were significantly better than other glucagon-like peptide-1 （GLP-1） receptor agonists in reducing glycosylated hemoglobin， body weight， and waist circumference （P＜0.05）. In terms of safety， compared with other GLP-1 receptor agonists， tirzepatide did not increase the incidence of gastrointestinal-related adverse events （AE）， the incidence of AE of grade ≥3， or the incidence of severe hypoglycemia （P＞0.05）. However， tirzepatide 15 mg may significantly increased the incidence of hypoglycemia and the rate of discontinuation due to adverse reactions （P＜ 0.05）. In terms of cost-effectiveness， based on the background of foreign pharmacoeconomic studies， tirzepatide was more cost- effective compared to semaglutide and liraglutide in the treatment of T2DM or for weight management. CONCLUSIONS Tirzepatide at doses of 10 mg and 15 mg has good efficacy and safety for the treatment of T2DM and for long-term weight management. However， when using the 15 mg dose of tirzepatide， close monitoring is required due to the risk of hypoglycemia and discontinuation due to adverse reactions it may pose. Based on pharmacoeconomic studies conducted abroad results， tirzepatide exhibits economic advantages.

Objective: To explore the effectiveness of different intervention modalities on nonsuicidal selfinjury (NSSI) in adolescents, so as to provide an evidencebased basis for the intervention strategy of NSSI in adolescents. Methods: Randomized controlled trials on interventions for adolescent NSSI were retrieved from databases, such as CNKI, Wanfang, VIP, CBM, Web of Science, PubMed, Embase, and Cochrane Library, spanning from the inception of these databases to March 5, 2025. Network Metaanalysis was performed by using Stata 17.0 and Review Manager 5.3 software, and the standardized mean difference (SMD) and 95%CI were used as the effect indicators to compare the differences in the effectiveness of the interventions and rank the effect. Results: A total of 26 articles with 2 034 adolescents with NSSI were included in the study, including 10 intervention modalities:dialectical behavior therapy, emotional regulation intervention, mentalizationbased therapy, family therapy, cutting down programme, cognitive behavioral therapy, narrative therapy, stepped care approach, positive psychological intervention, and acceptance and commitment therapy. The results showed that compared with the treatment as usual, positive psychological intervention [SMD(95%CI)=-2.12(-3.51 to -0.74)], stepped care intervention [SMD(95%CI)=-2.07(-3.43 to -0.71)], and dialectical behavior therapy [SMD(95%CI)=-1.70(-2.60 to -0.80)], cognitive behavioral therapy [SMD(95%CI)=-1.54(-2.61 to -0.48)], and acceptance and commitment therapy[SMD(95%CI)=-1.50(-2.68 to -0.32)] were statistically significant differences in reducing adolescents NSSI behaviors(P<0.05). Positive psychological intervention, stepped care intervention, and dialectical behavior therapy were more effective than the mentalizationbased therapy and the cutting down programme (SMD=-2.08, -2.03, -1.66, -2.06, -2.01, -1.64,P<0.05); the area under the cumulative ranking probability graph revealed that positive psychological intervention may have the best effect in improving NSSI among adolescents (82.5). Conclusions Positive psychological interventions show the best results in improving adolescent NSSI among multiple intervention modalities. It is recommended to give priority to positive psychological interventions in clinical interventions.

BACKGROUND:Acute exercise tends to cause skeletal muscle tissue damage and lipid metabolism disorders in vivo,but the mechanism by which acute exercise combined with electroacupuncture modulates metabolic and autophagic pathways in vivo is unclear. OBJECTIVE:To observe the changes in metabolic enzymes and autophagy levels in skeletal muscle of rats subjected to acute exercise by electroacupuncture at the acupoints of"Zusanli"and"Huantiao." METHODS:Fifty male Sprague-Dawley rats were randomly divided into three groups:quiet control group(n=10),model group(n=20),and reverse electroacupuncture group(n=20).The latter two groups were set up with two time points,i.e.immediate and 3 hours after exercise groups(n=10 per time point).The model group and the reverse electroacupuncture group underwent acute exercise training after adaptive treadmill training.The rats in the reverse electroacupuncture group underwent electroacupuncture treatment(parameters:electroacupuncture on both sides of the rats at the acupoints of"Zusanli"and"Huantiao,"continuous wave,frequency of 2 Hz,intensity of 2 mA,leaving the needle in the body for 30 minutes,once a day for 7 consecutive days)before treadmill training.Bilateral gastrocnemius muscle tissues were taken under anesthesia immediately after exercise and 3 hours after exercise,and hematoxylin-eosin staining was used to observe the histopathological changes of rat skeletal muscle.ELISA kit was used to detect the activities of hepatic lipase,fatty acid synthase,hormone-sensitive lipase,and carnitine palmitoyltransferase 1 in rat skeletal muscle tissues.Immunohistochemistry and western blot were used to detect the changes in the expression of autophagy genes. RESULTS AND CONCLUSION:After hematoxylin-eosin staining,the arrangement of gastrocnemius muscle fibers in the model group was disturbed,swollen and ruptured immediately after exercise and 3 hours after exercise.In the reverse electroacupuncture group,gastrocnemius muscle fibers were tightly arranged and the number of swollen and ruptured cells was greatly reduced immediately after exercise and 3 hours after exercise,and there was no significant difference when compared with the quiet control group.Compared with the quiet control group,the activities of hepatic lipase and fatty acid synthase were lower while the activities of lipoprotein lipase,hormone-sensitive lipase,and carnitine palmitoyltransferase 1 were higher in the model group and the reverse electroacupuncture group 3 hours after exercise(P＜0.05 or P＜0.01).Compared with the model group,the activities of lipoprotein lipase and carnitine palmitoyltransferase 1 were higher in the reverse electroacupuncture group immediately after exercise(P＜0.05),while the activity of lipoprotein lipase was higher and the activity of hormone-sensitive lipase was lower in the reverse electroacupuncture group 3 hours after exercise(P＜0.01).Immunohistochemical results showed that compared with the quiet control group,the expression of P62,autophagy-related gene 5 and autophagy-related gene 7 was higher in the model group immediately and 3 hours after exercise,as well as in the reverse electroacupuncture group immediately after exercise(P＜0.05 or P＜0.01);compared with the model group,the expression of P62 and autophagy-related gene 7 was lower in the reverse electroacupuncture group immediately and 3 hours after exercise(P＜0.05).Western blot results showed that the protein expression of P62 and autophagy-related gene 7 in the reverse electroacupuncture group was lower than that in the model group immediately after exercise(P＜0.05);the protein expression of Parkin in the model group was higher than that in the quiet control group immediately and 3 hours after exercise(P＜0.05);and the protein expression of Parkin in the reverse electroacupuncture group was lower than that in the model group immediately and 3 hours after exercise(P＜0.05).To conclude,acute exercise induces disorders,swelling and rupture of gastrocnemius muscle fibers in rats and electroacupuncture on both sides of the acupoints of"Zusanli"and"Huantiao"can improve the level of lipid metabolism and regulate autophagy cells in rat skeletal muscle,preventing the disorders of lipid metabolism and damage of gastrocnemius muscle tissues caused by acute exercise.The mechanism may be closely related to the regulation of autophagy-related factor P62,autophagy-related gene 5,autophagy-related gene 7,and Parkin protein expression to promote the occurrence of autophagy or regulate the autophagy pathway in rat skeletal muscle cells.

BACKGROUND:Impaired postural control is an important risk factor for falls and secondary damage in patients with idiopathic normal pressure hydrocephalus.Most of the existing studies have analyzed the gait parameters of patients during straight-line walking,but few have analyzed the postural stability characteristics of patients during static and dynamic activities. OBJECTIVE:To analyze the characteristics of postural stability in elderly patients with idiopathic normal pressure hydrocephalus. METHODS:Twenty-two patients clinically diagnosed with idiopathic normal pressure hydrocephalus at the Department of Neurosurgery,Huadong Hospital Affiliated to Fudan University,Shanghai,China,from September 2022 to February 2023 were selected as the patient group,and 18 healthy accompanying family members were selected as the healthy control group.The postural stability characteristics of the subjects were assessed using the Timed Up-and-Go Test,Multi-Directional Reach Test,Berg Balance Scale,and Static Balance Function Test(reaction time,speed of movement,directional control,maximum offset distance,and endpoint travel). RESULTS AND CONCLUSION:The time required to complete the Timed Up-and-Go Test was significantly longer in the patient group than in the healthy control group(P＜0.05).The results of the stretching test in the four directions of anterior,posterior,leftand right were significantly lower in the patient group than in the healthy control group(P＜0.05).The Berg Balance Scale scores in the patient group were lower than those in the healthy control group(P＜0.05).In the Static Balance Function Test,the results of reaction,movement speed,directional control,maximum offset distance and endpoint travel index were smaller in the patient group than the healthy control group(P＜0.05).To conclude,patients with idiopathic normal pressure hydrocephalus exhibit overall postural control deficits,and impaired reaction and execution abilities make these patients unable to make timely and accurate motor responses in the face of disturbances from internal or external sources,resulting in postural instability and increasing the risk of falls.

Macrophages are innate immune cells connected with the development of inflammation. Retinoic acid has previously been proved to have anti-inflammatory and anti-arthritic properties. However, the exact mechanism through which retinoic acid modulates arthritis remains unclear. This study aimed to investigate whether retinoic acid ameliorates rheumatoid arthritis by modulating macrophage polarization. This study used retinoic acid to treat mice with adjuvant arthritis and evaluated anti-inflammatory effects by arthritis score, thermal nociceptive sensitization test, histopathologic examination and immunofluorescence assays. In addition, its specific anti-arthritic mechanism was investigated by flow cytometry, cell transfection and inflammatory signaling pathway assays in RAW264.7 macrophages in vitro. Retinoic acid significantly relieved joint pain and attenuated inflammatory cell infiltration in mice. Furthermore, this treatment modulated peritoneal macrophage polarization, increased levels of arginase 1, as well as decreased inducible nitric oxide synthase expression. In vitro, we verified that retinoic acid promotes macrophage transition from the M1 to M2 type by upregulating mitogen-activated protein kinase (MAPK) phosphatase 1 (MKP-1) expression and inhibiting P38, JNK and ERK phosphorylation in lipopolysaccharide-stimulated RAW264.7 cells. Notably, the therapeutic effects of retinoic acid were inhibited by MKP-1 knockdown. Retinoic acid exerts a significant therapeutic effect on adjuvant arthritis in mice by regulating macrophage polarization through the MKP-1/MAPK pathway, and play an important role in the treatment of rheumatic diseases.

Monotropein is a compound classified into iridoid which is found in herbaceous plants Morindae officinalis. It possesses anti-inflammatory, antioxidant, and anti-osteoarthritic activities. Previous study indicates that monotropein may have the potential to combat cardiovascular disease, although the related mechanism remains unclear. In this study, we constructed the model of atherosclerosis by oxidized low density lipoprotein-induced vascular smooth muscle cells and LDLR –/–mice given high-fat diet to investigate the effects of monotropein on atherosclerosis.Our results showed that monotropein treatment significantly reduced the area of atherosclerotic plaques and necrotic cores in mice, inhibited the proliferation and migration of vascular smooth muscle cells, and reduced inflammatory responses and oxidative stress, which in turn alleviated atherosclerosis. In addition, we found that monotropein reduced the expression levels of P-NF-κB and P-AP-1. In conclusion, our data suggest that monotropein inhibited the proliferation and migration of vascular smooth muscle cells by mediating the activity of NF-κB, AP-1, reducing the level of inflammation and oxidative stress, and thus resisting the development of atherosclerosis. These findings demonstrate the efficacious therapeutic impact of monotropein on atherosclerosis and elucidate its specific target.

Macrophages are innate immune cells connected with the development of inflammation. Retinoic acid has previously been proved to have anti-inflammatory and anti-arthritic properties. However, the exact mechanism through which retinoic acid modulates arthritis remains unclear. This study aimed to investigate whether retinoic acid ameliorates rheumatoid arthritis by modulating macrophage polarization. This study used retinoic acid to treat mice with adjuvant arthritis and evaluated anti-inflammatory effects by arthritis score, thermal nociceptive sensitization test, histopathologic examination and immunofluorescence assays. In addition, its specific anti-arthritic mechanism was investigated by flow cytometry, cell transfection and inflammatory signaling pathway assays in RAW264.7 macrophages in vitro. Retinoic acid significantly relieved joint pain and attenuated inflammatory cell infiltration in mice. Furthermore, this treatment modulated peritoneal macrophage polarization, increased levels of arginase 1, as well as decreased inducible nitric oxide synthase expression. In vitro, we verified that retinoic acid promotes macrophage transition from the M1 to M2 type by upregulating mitogen-activated protein kinase (MAPK) phosphatase 1 (MKP-1) expression and inhibiting P38, JNK and ERK phosphorylation in lipopolysaccharide-stimulated RAW264.7 cells. Notably, the therapeutic effects of retinoic acid were inhibited by MKP-1 knockdown. Retinoic acid exerts a significant therapeutic effect on adjuvant arthritis in mice by regulating macrophage polarization through the MKP-1/MAPK pathway, and play an important role in the treatment of rheumatic diseases.

Monotropein is a compound classified into iridoid which is found in herbaceous plants Morindae officinalis. It possesses anti-inflammatory, antioxidant, and anti-osteoarthritic activities. Previous study indicates that monotropein may have the potential to combat cardiovascular disease, although the related mechanism remains unclear. In this study, we constructed the model of atherosclerosis by oxidized low density lipoprotein-induced vascular smooth muscle cells and LDLR –/–mice given high-fat diet to investigate the effects of monotropein on atherosclerosis.Our results showed that monotropein treatment significantly reduced the area of atherosclerotic plaques and necrotic cores in mice, inhibited the proliferation and migration of vascular smooth muscle cells, and reduced inflammatory responses and oxidative stress, which in turn alleviated atherosclerosis. In addition, we found that monotropein reduced the expression levels of P-NF-κB and P-AP-1. In conclusion, our data suggest that monotropein inhibited the proliferation and migration of vascular smooth muscle cells by mediating the activity of NF-κB, AP-1, reducing the level of inflammation and oxidative stress, and thus resisting the development of atherosclerosis. These findings demonstrate the efficacious therapeutic impact of monotropein on atherosclerosis and elucidate its specific target.