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.

The membranous tube of sanjiao （三焦） is not only the path of the transport of fluid and qi， but the way of the invasion of pathogenic factors， therefore， it cooperates with the skin mucous membrane physically and influence on each other pathologically. It is believed that the core pathogenesis of chronic urticaria is pathogens intruding sanjiao， membrane collaterals acute spasm， and fluid and qi disturbance， of which defense qi insufficiency and pathogens intruding sanjiao initiates the disease， while struggle between healthy and pathogenic qi and membrane collaterals acute spasm is the intermediate stage， and disturbed fluid， qi and blood movement is the terminal stage. Following the core treatment principle of dredging sanjiao， the internal treatment is to open striae and interstices and dispel pathogens out using self-made Guben Shufeng Decoction（固本疏风汤）modifications， and the external treatment is to dredge and regulate membrane collaterals， move qi and fluid， and treat sanjiao simultaneously， commonly using cutting therapy on Danzhong （RN 17） to move qi and fluid， seal umbilical therapy on Shenque （RN 8） to supplement and nourish ying-wei （营卫）， and natural moxibustion on Xuehai （SP 10） to move blood and unblock collaterals.

Objective Viral encephalitis is an infectious disease severely affecting human health.It is caused by a wide variety of viral pathogens,including herpes viruses,flaviviruses,enteroviruses,and other viruses.The laboratory diagnosis of viral encephalitis is a worldwide challenge.Recently,high-throughput sequencing technology has provided new tools for diagnosing central nervous system infections.Thus,In this study,we established a multipathogen detection platform for viral encephalitis based on amplicon sequencing. Methods We designed nine pairs of specific polymerase chain reaction(PCR)primers for the 12 viruses by reviewing the relevant literature.The detection ability of the primers was verified by software simulation and the detection of known positive samples.Amplicon sequencing was used to validate the samples,and consistency was compared with Sanger sequencing. Results The results showed that the target sequences of various pathogens were obtained at a coverage depth level greater than 20×,and the sequence lengths were consistent with the sizes of the predicted amplicons.The sequences were verified using the National Center for Biotechnology Information BLAST,and all results were consistent with the results of Sanger sequencing. Conclusion Amplicon-based high-throughput sequencing technology is feasible as a supplementary method for the pathogenic detection of viral encephalitis.It is also a useful tool for the high-volume screening of clinical samples.

Methods To investigate how the timing of cooling therapy affects organ injuries in rats with exertional heat stroke(EHS)and explore the possible mechanisms.Methods A total of 60 adult male Wistar rat models of EHS were randomized into model group without active cooling after modeling,immediate cooling group with cold water bath immediately after modeling,delayed cooling groups with cold water bath at 5,15 and 30 min after modeling,with another 12 mice without EHS as the normal control group.The changes in core body temperature of the mice were recorded and the cooling rate was calculated.After observation for 24 h,the mice were euthanized and blood samples were collected for detection of interleukin-1β(IL-1β),IL-2,IL-4,IL-6,IL-10,and interferon-γ,followed by pathological examination of the vital organs.The rats that died within 24 h were immediately dissected for examination.Results The number of deaths of the model rats within 24 h increased significantly with the time of delay of cooling treatment.The delay of cooling was positively correlated(r=0.996,P=0.004)while the cooling rate negatively correlated with the mortality rate(r=-0.961,P=0.009).The inflammatory cytokine levels presented with different patterns of variations among the cooling intervention groups.All the rat models of EHS had significant organ damages characterized mainly by epithelial shedding,edema,effusion,and inflammatory cell infiltration,and brain and renal injuries reached the peak level at 24 h after EHS.Conclusion EHS causes significant nonspecific pathologies of varying severities in the vital organs of rats,and the injuries worsen progressively with the delay of cooling.There is a significant heterogeneity in changes of serum inflammatory cytokines in rats with different timing of cooling intervention following EHS.

Purpose To explore the value of contrast-enhanced ultrasound(CEUS)in the differential diagnosis of gallbladder polypoid lesions(GPLs)(diameter≥10 mm).Materials and Methods A prospective enrollment of 229 patients with GPLs who underwent cholecystectomy in 17 hospitals from December 1 2021 to June 30 2024 was conducted to analyze the relationship between general data,conventional ultrasound,CEUS characteristics and the nature of GPLs.Multivariate Logistic regression was employed to identify independent risk factors for neoplastic polyps,the differential diagnostic value of different indicators was compared.Results Among 229 patients with GPLs,there were 108 cases of cholesterol polyps,102 cases of adenoma and 19 cases of gallbladder cancer.Age(Z=-4.476,P<0.001),polyp number(χ2=15.561,P<0.001),diameter(Z=-8.149,P<0.001),echogenicity(χ2=9.241,P=0.010),vascularity(χ2=23.107,P<0.001),enhancement intensity(χ2=47.610,P<0.001),enhancement pattern(χ2=6.468,P=0.011),vascular type(χ2=84.470,P<0.001),integrity of gallbladder wall(χ2=7.662,P=0.006)and stalk width(Z=-9.831,P<0.001)between cholesterol polyps and neoplastic polyps were statistically significant.Age,location,diameter,echogenicity,enhancement pattern,vascular type and stalk width between adenoma and gallbladder cancer were statistically significant(Z=-4.333,-3.902,-5.042,all P<0.05).Multivariate Logistic regression analysis showed that hyper-enhancement,branched vascular type and stalk width were independent risk factors for neoplastic polyps(OR=4.563,5.770,3.075,all P<0.001).The combination of independent risk factors was better than single factor and diameter in the differential diagnosis of cholesterol polyps and neoplastic polyps(all P<0.01).Conclusion CEUS can effectively identify the nature of GPLs and provide a valuable imaging reference for the selection of treatment methods.

Recent studies have shown that stress can substantially facilitate breast cancer metastasis,which can be reduced by nonselective β1/β2-adrenergic receptor(β1/β2-AR)blocker.However,several side effects were identified.Thus,it is extremely warranted to explore more effective and better-tolerated β2-AR blocker.Currently,we demonstrated that baicalin(BA),a major bioactive component of Scutellaria bai-calensis Georgi,could significantly attenuate stress hormones especially epinephrine(Epi)-induced breast cancer cell migration and invasion in vitro.Mechanistically,we identified that β2-AR was a direct target of BA via the drug affinity responsive target stability(DARTS)combined with mass spectrum assay,and BA photoaffinity probe with pull-down assay,which was further confirmed by a couple of bio-physical and biochemical assays.Furthermore,we demonstrated that BA could directly bind to the Phe-193 and Phe-289 of β2-AR,subsequently inhibit cyclic adenosine monophosphate-protein kinase A-focal adhesion kinase(cAMP-PKA-FAK)pathway,and thus impede epithelial-mesenchymal transition(EMT),thereby hindering the metastatic progression of the chronic stress coupled with syngeneic and xenograft in vivo orthotopic and tail vein mouse model.These findings firstly identify BA as a potential β2-AR inhibitor in the treatment of stress-induced breast cancer metastasis.

Sulfur dioxide(SO2)is involved in regulating various physiological processes of blood vessels,such as maintaining normal vascular structure,regulating vascular tension,controlling blood pressure,inhibiting vascular cell proliferation,regulating apoptosis and autophagy.In pathophysiological conditions such as hypertension,pulmonary hypertension and atherosclerosis,SO2 plays a protective role in pathological changes through different molecular mechanisms.In this paper,we will review the endogenous SO2 production and metabolism,vascular biological effects and its regulation on blood vessels.

Hydrogen sulfide(H2S)is an emerging endogenous neuromodulator that holds significant potential in the realm of neurological diseases.Its role encompasses reducing neuronal damage,inhibiting excessive activation of striatal astrocytes,and regulating cerebrovascular function,among other physiopathological pathways.Conversely,microRNAs(miRNAs)are widely recognized as pivotal regulators of neurological diseases.They primarily target the 3'untranslated region of the target gene mRNA,impeding mRNA translation and hindering its expression to impart neuroprotective effects.Recent findings have underscored the crucial involvement of H2S and miRNAs in the pathogenesis of various neurological disorders such as Parkinson's disease,stroke,and spinal cord diseases,thereby garnering significant attention.This paper comprehensively summarizes the protective effects arising from the interplay between H2S and miRNAs in neurological diseases,while also delving into the potential therapeutic efficacy they hold for such conditions.

Methods To investigate how the timing of cooling therapy affects organ injuries in rats with exertional heat stroke(EHS)and explore the possible mechanisms.Methods A total of 60 adult male Wistar rat models of EHS were randomized into model group without active cooling after modeling,immediate cooling group with cold water bath immediately after modeling,delayed cooling groups with cold water bath at 5,15 and 30 min after modeling,with another 12 mice without EHS as the normal control group.The changes in core body temperature of the mice were recorded and the cooling rate was calculated.After observation for 24 h,the mice were euthanized and blood samples were collected for detection of interleukin-1β(IL-1β),IL-2,IL-4,IL-6,IL-10,and interferon-γ,followed by pathological examination of the vital organs.The rats that died within 24 h were immediately dissected for examination.Results The number of deaths of the model rats within 24 h increased significantly with the time of delay of cooling treatment.The delay of cooling was positively correlated(r=0.996,P=0.004)while the cooling rate negatively correlated with the mortality rate(r=-0.961,P=0.009).The inflammatory cytokine levels presented with different patterns of variations among the cooling intervention groups.All the rat models of EHS had significant organ damages characterized mainly by epithelial shedding,edema,effusion,and inflammatory cell infiltration,and brain and renal injuries reached the peak level at 24 h after EHS.Conclusion EHS causes significant nonspecific pathologies of varying severities in the vital organs of rats,and the injuries worsen progressively with the delay of cooling.There is a significant heterogeneity in changes of serum inflammatory cytokines in rats with different timing of cooling intervention following EHS.

Objective:To explore the short-term efficacy on 3D printing assisted reconstruction of traumatic digit joint defects using rib and costo-osteochondral autograft.Methods:From August 2022 to July 2023, 7 patients with open digit joint defects had undergone emergency primary debridement and fracture fixation in the Department of Orthopaedics, 988th Hospital of the Joint Logistics Support Force of PLA. Patients with more phalangeal defects that could not be aligned were treated with antibiotic bone cement filling in the emergency surgery. In the second stage surgery, bone cement was removed and transfer of rib cartilage graft was performed to reconstruct the digit joint defect. According to a 1∶1 3D printed hand templates, rib cartilage grafts were crafted to the shape of digit joints, and then spliced together the digit joints and bone defects for fixation. Follow-up X-ray examinations were taken and assessment of the healing status of rib and fractures of phalangeal and metacarpophalangeal bones were carried out according to the Paley fracture healing score. At the outpatient follow-up, assessment of transferred joint movement and evaluation of upper limb function were conducted according to the Evaluation Trial Standards of Upper Limb Partial Functional of Hand Surgery of Chinese Medical Association. Visual Analogue Scale (VAS) pain scores were evaluated from the affected digits and donor sites.Results:After reconstructive surgery, all 7 patients had primary healing of the wounds of hand. One patient had fat liquefaction at the donor site, and the rest had primary donor site healing. One patient received further surgery for extensor tendon repair after rib cartilage grafting due to the digital extensor tendon injury. All 7 patients were included in postoperative follow-up for 6-11 months, with an average of 9 months. All patients had excellent fracture healing according to the Paley fracture healing score. At the final follow-up, the extension and flexion of the digit joints were found at 40°-80° (average 56.2°) for proximal interphalangeal joints (4 patients), and 10° in extension and 85° in flexion for metacarpophalangeal joint (1 patient). The range of motion of the thumb interphalangeal joint (2 patients) was 20°-35° (average 27.5°). Hand function was assessed according to Evaluation Trial Standards of Upper Limb Partial Functional of Hand Surgery of Chinese Medical Association and it was found that 3 patients were in excellent, 3 in good and 1 in fair.Conclusion:This study focused on the treatment of traumatic digit joint defects by transfer of individually crafted rib cartilages in reconstruction of the defected digit joint. It significantly improves the appearance and function of the defected digit joints, especially suitable for the irregular defects of phalangeal bones.