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 discuss the clinical safety,feasibility and efficacy of transcatheter arterial infusion chemotherapy(TAI)combined with lipiodol chemoembolization in the treatment of advanced colorectal cancer(CRC).Methods The clinical data of 37 patients with advanced CRC,who received TAI combined with lipiodol chemoembolization at the First Affiliated Hospital of Zhengzhou University of China between June 2016 and December 2022,were retrospectively analyzed.The clinical efficacy was evaluated,the progression-free survival(PFS)and the serious complications were recorded.Results A total of 55 times of TAI combined with lipiodol chemoembolization procedures were successfully accomplished in the 37 patients.The mean used amount of lipiodol emulsion was 2.9 mL(0.8-10 mL).No serious complications such as bleeding and intestinal perforation occurred.The median follow-up time was 24 months(range of 3-48 months).The postoperative one-month,3-month,6-month and 12-month objective remission rates(ORR)were 67.6%(25/37),67.6%(25/37),64.9%(24/37)and 56.8%(21/37)respectively,and the postoperative one-month,3-month,6-month and 12-month disease control rates(DCR)were 91.9%(34/37),91.9%(34/37),89.2%(33/37)and 81.1%(30/37)respectively.The median PFS was 16 months(range of 2-47 months).As of the last follow-up,22 patients survived and 15 patients died of terminal stage of tumor.Conclusion Preliminary results of this study indicate that TAI combined with lipiodol chemoembolization is clinically safe and effective for advanced CRC,and it provide a new therapeutic method for patients with advanced CRC.

Objective:To explore the impact of baseline remnant cholesterol levels at a single time point and cumulative remnant cholesterol exposure on the progression trajectories of arterial stiffness.Methods:This prospective cohort study included 2 401 eligible participants from the Beijing Health Management Cohort who consecutively attended health examinations in 2010-2011, 2012-2013, and 2014-2015. The remnant cholesterol value measured in 2014-2015 served as the baseline remnant cholesterol level at a single time point. The cumulative exposure indices were calculated based on remnant cholesterol values from three health examinations from 2010 to 2015, including cumulative exposure, cumulative exposure burden, and duration of high remnant cholesterol exposure. Arterial stiffness was assessed by brachial-ankle pulse wave velocity (baPWV). The follow-up continued until December 31, 2019, with annual check-ups. During the follow-up period, a group-based trajectory model was employed to construct the progression trajectories of baPWV. The associations between the baseline remnant cholesterol level, cumulative exposure indices of remnant cholesterol and baPWV trajectories were examined using ordinal logistic regression models, adjusting for traditional cardiovascular risk factors and low-density lipoprotein cholesterol (LDL-C) levels.Results:The age of the 2 401 participants was 61 (54, 69) years, with 1 801 (75.01%) being male. The group-based trajectory model indicated that the best-fit model categorized the participants into three subgroups: low-rising group (1 036 individuals, 43.15%), moderate-rising group (1 137 individuals, 47.36%), and high-rising group (228 individuals, 9.50%). After adjusting for traditional cardiovascular risk factors, baseline remnant cholesterol levels at a single point ( OR=1.170, 95% CI: 1.074-1.274), cumulative remnant cholesterol exposure ( OR=1.194, 95% CI: 1.096-1.303), cumulative remnant cholesterol exposure burden ( OR=1.270, 95% CI: 1.071-1.507), and high-remnant cholesterol exposure duration (6 years: OR=1.351, 95% CI: 1.077-1.695) were significantly associated with the risk of developing a poor baPWV progression trajectory. These results remained significant after adjusting for cumulative average LDL-C levels. The association between baseline remnant cholesterol levels and baPWV progression became insignificant after adjusting for cumulative remnant cholesterol levels ( OR=1.053, 95% CI: 0.923-1.197), while the association between cumulative remnant cholesterol exposure and baPWV progression remained significant after adjusting for baseline remnant cholesterol levels ( OR=1.145, 95% CI: 1.008-1.305). Conclusions:Higher levels of baseline remnant cholesterol and cumulative remnant cholesterol are independent risk factors for the progression of arterial stiffness. These associations remain significant even after adjusting for traditional cardiovascular risk factors and LDL-C levels. Furthermore, the effect of cumulative remnant cholesterol levels on the progression of arterial stiffness was stronger than the effect of baseline remnant cholesterol levels.

Rare diseases still lack effective treatments, and the development of drugs for rare diseases (known as orphan drugs) is an urgent medical problem. As natural active ingredients in living organisms, some biomacromolecule drugs have good biocompatibility, low immunogenicity, and high targeting. They have become one of the most promising fields in drug research and development in the 21st century. However, there are still many obstacles in terms of in vivo delivery. In view of the unique advantages of nanocarriers prepared from polymers, lipids, organic biomimetic and inorganic materials in drug delivery, researchers are committed to building an efficient delivery system with versatility and synergy to solve the bottleneck issues in treating rare diseases with biomacromolecule drugs. Therefore, this article reviews the research progress of nanocarrier delivering proteins, peptides and nucleic acids in the field of rare disease treatment in the past ten years, which provides ideas for researches on biomacromolecule drug nanosystems in the field of treatment of rare diseases.

Objective:To explore the changes in resting energy expenditure (REE) values in patients with severe burns under different metabolic stages and the selection of the optimal calculation formula.Methods:This study was a retrospective and observational study. From April 2020 to December 2023, 40 patients (32 males and 8 females, aged (54±17) years) with severe burns meeting inclusion criteria were treated in the Second Affiliated Hospital of Zhejiang University School of Medicine. After admission, the patients were given routine clinical treatments such as sedation and analgesia, debridement, and skin grafting. At 3, 5, 7, 9, 11, 14 days after injury and every 7 days thereafter, the REE values (i.e., REE measured values) were measured by indirect calorimetry in patients with severe burns who met the measurement conditions till the patients recovered or died. On the day the patient's REE was measured, Milner, Hangang, the Third Military Medical University, Carlson, and Peng Xi team's linear formula were used respectively to calculate the REE value (i.e., REE formula values). The post-injury time to measure REE in patients was calculated, and the clinical characteristics of patients in acute inhibition, hypermetabolic, metabolic balance, and metabolic remodeling phases were compared. The REE measured values and the difference between the REE formula values and the REE measured values of patients under the 4 different metabolic phases were calculated.Compared with the REE measured values, the 10% accuracy rate and 20% accuracy rate were calculated to evaluate the accuracy of the REE formula values. The absolute percentage error (APE) of the REE formula values were calculated to evaluate the deviation. The metabolic formula (i.e., the optimal calculation formula) that was closest to the measured REE values was screened out, and further exploration was conducted to identify the key factors that affected the accuracy of the optimal calculation formula under different metabolic phases.Results:The post-injury time to measure REE in patients with severe burns was (40±19) days. Comparisons showed that under the 4 different metabolic phases, patients in the metabolic remodeling phase had the highest age, height, weight, body mass index, total body surface area. Age in the metabolic remodeling phase was significantly higher than that in the acute inhibition and hypermetabolic phases (with t values of -3.02 and -4.20, respectively, with all P values <0.05), weight was significantly higher than that in the hypermetabolic and metabolic balance phases (with t values of -1.97 and -2.61, respectively, with all P values <0.05), body mass index was significantly higher than that in the hypermetabolic phase ( t=-2.90, P<0.05), and total body surface area was significantly larger than that in the hypermetabolic and metabolic balance phases (with t values of -2.02 and -2.27, respectively, with all P values <0.05). There was no significant change in patients' REE measured values under the 4 different metabolic stages ( P>0.05). Except for the Peng Xi team's linear formula ( P>0.05), the difference between REE measured values and REE formula values calculated by using Milner, Hangang, the Third Military Medical University, and Carlson formulas respectively was statistically significant under different metabolic stages (with H values of 14.50, 27.15, and 37.26, respectively, F=11.80, P<0.05). Comprehensive analysis of 10% accuracy, 20% accuracy, and APE showed that in the acute inhibition phase, the REE formula values calculated by Peng Xi team's linear formula was closest to REE measured values, and the APE of the REE formula values calculated by Peng Xi team's linear formula was significantly lower than those calculated by Milner formula, Hangang formula, the Third Military Medical University formula, and Carlson formula (with t values of 9.00, -2.10, 5.95, and 6.68, respectively, with all P values <0.05). In the hypermetabolic phase, the REE formula values calculated by Hangang formula were closest to REE measured values, with significantly lower APE of the REE formula values calculated by Hangang formula than those calculated by using Milner formula, the Third Military Medical University formula, Carlson formula, and Peng Xi team's linear formula (with t values of 10.20, 10.33, 10.65, and 5.87, respectively, with all P values <0.05). In the metabolic balance phase, the REE formula values calculated by Hangang formula were again closest to REE measured values, with significantly lower APE of the REE formula values calculated by Hangang formula than those calculated by Milner formula, the Third Military Medical University formula, and Carlson formula (with t values of 7.11, 8.52, and 8.60, respectively, with all P values <0.05). In the metabolic remodeling phase, the REE formula values calculated by the Third Military Medical University were closest to REE measured values, with significantly lower APE of the REE formula values calculated by the Third Military Medical University formula than those calculated by Milner formula, Hangang formula, and Carlson formula (with t values of 5.12, 2.45, and 6.26, respectively, with all P values <0.05). No significant key factors affected the accuracy of the Peng Xi team's linear formula in the acute inhibition phase ( P>0.05). In the hypermetabolic phase, total burn area was a key factor affecting the accuracy of Hangang formula (with odds ratio of 1.00, with 95% confidence interval of 1.00-1.10, P<0.05). In the metabolic balance phase, post-injury days was a key factor affecting the accuracy of Hangang formula (with odds ratio of 1.30, with 95% confidence interval of 1.10-1.40, P<0.05). In the metabolic remodeling phase, no significant key factors affected the accuracy of the Third Military Medical University formula ( P>0.05). Conclusions:When calculating REE values in patients with severe burns, it is recommended to use the Peng Xi team's linear formula during the acute inhibition phase, the Hangang formula during the hypermetabolic and metabolic balance phases, and the Third Military Medical University formula during the metabolic remodeling phase. Additionally, it is crucial to ensure the accuracy of key factors affecting the optimal calculation formula in the hypermetabolic and metabolic balance phases.

The biological characteristics and pathogenicity of Klebsiella oxytoca isolated from sick carrier pigeons in Gansu province were explored by morphological observations,biochemical testing,16S rRNA PCR analysis,and RNA sequencing.The drug resistance and pathogenicity of the isolated strains were studied by histopathological observation,drug susceptibility testing,and pathogenicity analysis.The livers,lungs,hearts,and other organs of the sick pigeons were bleeding.In addition,the livers were yellow and brittle,and the lungs were purulent.A Gram-negative,short,rod-shaped bacterium was successfully isolated from the sick pigeon.Pink,smooth,moist,and round colonies grew on MacConkey's agar.The result of the indigo matrix test was positive.The homology between the amplified 16S rRNA sequence and MN330093.1 was 100.00％,indicating that the sick pigeon was infected with K.oxytoca.The strain was named GS-BY-GG.K.Oxytoca GS-BY-GG was resistant to 10 drugs,including penicillin,ampicillin,and furazolidone,and sensitive to 5 others,which included florfenicol,meropenem,and gentamicin.Histopathological observation showed bleeding in multiple organs.The liver cells were irregu-larly arranged with brown-yellow pigmentation.Extensive cell necrosis and exfoliation were observed in the trachea and mucosal epithelium,with inflammatory cell infiltration in the mucosal layer.The isolates were highly pathogenic in specific pathogen-free chickens.These findings provide support for the clinical diagnosis and control of K.oxytoca GS-BY-GG.

Panax notoginseng is the dried root and rhizome of Panax notoginseng(Burk.)F.H.Chen,a perennial erect herb of the genus Ginseng of the family Wujiaceae.As a traditional Chinese medicine in our country,Panax notoginseng has a good tonic effect,and the Dictionary of Traditional Chinese Medicines has the words that Panax notoginseng is used to tonify the blood,remove the blood stasis and damage,and stop epistaxis.It can also be used to pass the blood and tonify the blood with the best efficacy,and it is the most precious one of the prescription med-icines.Eaten raw,it removes blood stasis and generates new blood,subdues swelling and stabilizes pain,stops bleeding with-out leaving stasis,and promotes blood circulation without hurting the new blood;taken cooked,it can be used to replenish and strengthen the body.Notoginsenoside R1 is a characteristic com-pound in the total saponin of Panax ginseng.In recent years,China's aging has been increasing,and the incidence of neuro-logical disorders has been increasing year by year.Meanwhile,reports on notoginsenoside R1 in the treatment of neurological disorders are increasing,and its neuroprotective effects have been exerted with precise efficacy.The purpose of this paper is to review the treatment of neurological diseases and the mecha-nism of action of notoginsenoside R1,so as to provide a certain theoretical basis for clinical use and new drug development.

[Purpose]To analyze the trend of bladder cancer incidence and age at diagnosis in can-cer registration areas of Jiangsu Province from 2009 to 2019.[Methods]The data of bladder can-cer incidence from 2009 to 2019 were collected from 16 cancer registries in Jiangsu Province,and quality control indicators of the data were evaluated.The crude rate(CR)of incidence,age-standar-dized incidence rate by Segi world standard population(ASIRW),age-specific incidence rate,mean age at diagnosis,mean standardized age at diagnosis,and age-specific incidence composi-tion ratio were calculated.Incidence trends were analyzed using Joinpoint software and the average annual percentage change(AAPC)was calculated.Birth cohort models were constructed and can-cer incidence rates were calculated for people born from 1929 to 2019 and the incidence trends were analyzed.The linear regression models were used to analyze the relationship of average age at onset,standardized average age of onset with year of onset.[Results]The CR of bladder cancer in Jiangsu Province increased from 4.27/105 in 2009 to 7.04/105 in 2019.The CR and ASIRW showed upward trends(CR:AAPC=4.62％,ASIRW:AAPC=1.92％,both P＜0.001).Sex-specific analysis showed that the incidence rate was higher in male(AAPC=5.32％)than that in female(AAPC=1.98％).Birth cohort results indicated a significant upward trend in incidence rates among age groups of 60 years old above,and the fastest increase was in those aged 80 years old and above(AAPC=3.27％,P=0.007).From 2009 to 2019,the average age of bladder cancer onset in Jiangsu Province showed a significant rising trend,increasing by an average of 0.17 years old annually,but the standardized average age of onset showed no significant change after adjusting for age structure.[Conclusion]The incidence rate of bladder cancer showed an increasing trend from 2009 to 2019 in Jiangsu Province,with a significantly higher incidence rate in male than that in female.

Traumatic supraorbital fissure syndrome (TSOFS) is a symptom complex caused by nerve entrapment in the supraorbital fissure after skull base trauma. If the compressed cranial nerve in the supraorbital fissure is not decompressed surgically, ptosis, diplopia and eye movement disorder may exist for a long time and seriously affect the patients′ quality of life. Since its overall incidence is not high, it is not familiarized with the majority of neurosurgeons and some TSOFS may be complicated with skull base vascular injury. If the supraorbital fissure surgery is performed without treatment of vascular injury, it may cause massive hemorrhage, and disability and even life-threatening in severe cases. At present, there is no consensus or guideline on the diagnosis and treatment of TSOFS that can be referred to both domestically and internationally. To improve the understanding of TSOFS among clinical physicians and establish standardized diagnosis and treatment plans, the Skull Base Trauma Group of the Neurorepair Professional Committee of the Chinese Medical Doctor Association, Neurotrauma Group of the Neurosurgery Branch of the Chinese Medical Association, Neurotrauma Group of the Traumatology Branch of the Chinese Medical Association, and Editorial Committee of Chinese Journal of Trauma organized relevant experts to formulate Chinese expert consensus on the diagnosis and treatment of traumatic supraorbital fissure syndrome ( version 2024) based on evidence of evidence-based medicine and clinical experience of diagnosis and treatment. This consensus puts forward 12 recommendations on the diagnosis, classification, treatment, efficacy evaluation and follow-up of TSOFS, aiming to provide references for neurosurgeons from hospitals of all levels to standardize the diagnosis and treatment of TSOFS.

Patients with severe trauma require an extremely timely treatment and transfusion plays an irreplaceable role in the emergency treatment of such patients. An increasing number of evidence-based medicinal evidences and clinical practices suggest that patients with severe traumatic bleeding benefit from early transfusion of low-titer group O whole blood or hemostatic resuscitation with red blood cells, plasma and platelet of a balanced ratio. However, the current domestic mode of blood supply cannot fully meet the requirements of timely and effective blood transfusion for emergency treatment of patients with severe trauma in clinical practice. In order to solve the key problems in blood supply and blood transfusion strategies for emergency treatment of severe trauma, Branch of Clinical Transfusion Medicine of Chinese Medical Association, Group for Trauma Emergency Care and Multiple Injuries of Trauma Branch of Chinese Medical Association, Young Scholar Group of Disaster Medicine Branch of Chinese Medical Association organized domestic experts of blood transfusion medicine and trauma treatment to jointly formulate Chinese expert consensus on blood support mode and blood transfusion strategies for emergency treatment of severe trauma patients ( version 2024). Based on the evidence-based medical evidence and Delphi method of expert consultation and voting, 10 recommendations were put forward from two aspects of blood support mode and transfusion strategies, aiming to provide a reference for transfusion resuscitation in the emergency treatment of severe trauma and further improve the success rate of treatment of patients with severe trauma.