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.

ObjectiveTo analyze the epidemiological characteristics of influenza virus in severe acute respiratory tract infection (SARI) cases in Jingzhou City, so as to provide a scientific basis for the formulation of influenza prevention and control policies in Jingzhou City. MethodsSARI surveillance was carried out in two sentinel hospitals in Jingzhou City from 2018 to 2023. Respiratory tract samples were collected from cases and influenza virus nucleic acid was measured using real-time fluorescent polymerase chain reaction (RT-PCR). ResultsA total of 2 603 SARI samples were tested from 2018 to 2023, and 338 samples were positive for influenza virus nucleic acid, with a detection rate of 12.99%. The highest positive detection rate was 20.22% in 2019, followed by 14.29% in 2022, and the lowest detection rate was 7.75% in 2020. There were significant differences for the positive detection rates of influenza in each monitoring year (χ²=30.386, P<0.001). There were epidemic peaks in the five surveillance years from 2018 to 2023 except 2020. There were winter epidemic peaks during 2018‒2019 and 2021‒2022, and an obvious summer epidemic peak was also observed from 2019 to 2022. H1N1, H3N2, B-Victoria and B-Yamagata were alternately prevalent in the six surveillance years. In 2019, H1N1, H3N2 and B-Victoria were alternately prevalent with time progress, in 2021 only B-Victoria was prevalent, and in 2022 H3N2 and B-Victoria were prevalent. There was no statistically significant difference for the positive detection rates of influenza virus between different genders (χ²=0.178, P=0.673). Among the four age groups, the positive rate of influenza virus in the age group of 15‒<25 years old was the highest (40.91%), followed by the age group of 25‒<60 years old (21.31%). There were statistically significant differences for the positive rates of influenza virus among different age groups (χ²=24.496, P<0.001). ConclusionThe surveillance of SARI cases in Jingzhou City could serve as an effective supplement to the surveillance of ILI in sentinel hospitals. It is suggested to expand the surveillance scope, strengthen public education and outreach on the prevention and control of respiratory diseases, thereby providing a scientific basis for influenza prevention and control.

Umbilical cord mesenchymal stem cells (UC-MSCs) have been widely used in regenerative medicine, but there is limited research on the stability of UC-MSCs formulation during production. This study aims to assess the stability of the cell stock solution and intermediate product throughout the production process, as well as the final product following reconstitution, in order to offer guidance for the manufacturing process and serve as a reference for formulation reconstitution methods. Three batches of cell formulation were produced and stored under low temperature (2-8 ℃) and room temperature (20-26 ℃) during cell stock solution and intermediate product stages. The storage time intervals for cell stock solution were 0, 2, 4, and 6 h, while for intermediate products, the intervals were 0, 1, 2, and 3 h. The evaluation items included visual inspection, viable cell concentration, cell viability, cell surface markers, lymphocyte proliferation inhibition rate, and sterility. Additionally, dilution and culture stability studies were performed after reconstitution of the cell product. The reconstitution diluents included 0.9% sodium chloride injection, 0.9% sodium chloride injection + 1% human serum albumin, and 0.9% sodium chloride injection + 2% human serum albumin, with dilution ratios of 10-fold and 40-fold. The storage time intervals after dilution were 0, 1, 2, 3, and 4 h. The reconstitution culture media included DMEM medium, DMEM + 2% platelet lysate, 0.9% sodium chloride injection, and 0.9% sodium chloride injection + 1% human serum albumin, and the culture duration was 24 h. The evaluation items were viable cell concentration and cell viability. The results showed that the cell stock solution remained stable for up to 6 h under both low temperature (2-8 ℃) and room temperature (20-26 ℃) conditions, while the intermediate product remained stable for up to 3 h under the same conditions. After formulation reconstitution, using sodium chloride injection diluted with 1% or 2% human serum albumin maintained a viability of over 80% within 4 h. It was observed that different dilution factors had an impact on cell viability. After formulation reconstitution, cultivation in medium with 2% platelet lysate resulted in a cell viability of over 80% after 24 h. In conclusion, the stability of cell stock solution within 6 h and intermediate product within 3 h meets the requirements. The addition of 1% or 2% human serum albumin in the reconstitution diluent can better protect the post-reconstitution cell viability.

Objective To analyze the burden and changing trend of testicular cancer in China from 1990 to 2019.Methods Based on the 2019 Global Burden of Disease Database(GBD 2019),analyze the incidence,mortality,disability-adjusted life years(DALYs),years of life lost(YLLs),years lived with disability(YLDs)and their variation trend of testicular cancer in Chinese population from 1990 to 2019.Evaluating changes in age standardized rate(ASR)by calculating annual estimated percentage change(EAPC).According to the age grouping,analyze the age distribution characteristics of testicular cancer disease burden by age group.Results In 2019,the incident cases,deaths,age-standardized incidence rate,and age-standardized mortality rate of testicular cancer in China were 17.17×103,1.21×103,2.39/105,and 0.16/105,respectively.Compared to 1990,incident cases,deaths,and age-standardized incidence rate increased obviously in China,which was consistent with the global change trend,while the increase was higher than the global level.However,both Chinese and global age-standardized mortality rate showed a downward trend.From 1990 to 2019,DALYs,YLLs and YLDs of testicular cancer increased by 29.66%,9.83%and 720.91%respectively in China.The two age groups,0-15 years group and 30-35 years group,were with highest incidence of testicular cancer,while the highest disease burden of testicular cancer was 30-35 years.Conclusion From 1990 to 2019,the disease burden of testicular cancer in China showed an upward trend.Adolescents and young adults should be the priority population for screening and prevention due to their higher incidence and disease burden.

Objective:To summarize the clinical characteristics and first aid measures of children with drowning，and to provide scientific basis for the treatment and prevention of drowning in children.Methods:The clinical data of drowning children admitted to the Children's Medical Center of the First Affiliated Hospital of Hunan Normal University（Hunan Provincial People's Hospital）from January 2011 to December 2021 were retrospectively summarized. Baseline characteristics，prehospital emergency care and prognosis of the included children were analyzed.According to the time span, drowning children were divided into two stages, the first stage (2011-2016) and the second stage (2017-2021). According to cerebral performance category assessment scale,drowning children with cardiac arrest were divided into two groups: a group with good neurological prognosis and a group with poor neurological prognosis. The baseline characteristics,pre-hospital emergency care, and prognosis of drowning children during different periods and with different prognosis were analyzed.Results:A total of 53 children were enrolled during the study period，with 24 cases in the first phase（2011-2016）and 29 cases in the second phase（2017-2021）.Boys accounted for 73.6%（39/53）of the cases, the age ranged from 1 month and 24 days to 14 years old，with 1-4 years old being the most common，accounting for 58.5%（31/53）, and the season in which drowning occurred was more common in the summer（39.6%, 21/53）.Six cases (11.3%) had significant neurological sequelae, and the mortality rate was 3.8%（2/53）.There was a decrease in the proportion of drowning with water control in the second stage compared to the first stage（37.5% vs. 13.79%, P=0.046）.Thirty-two（60.4%）children experienced on-site cardiopulmonary resuscitation(CPR) after drowning，with 24 cases in the group with good neurological prognosis and 8 cases in the group with poor neurological prognosis.Children in the poor neurological prognosis group required CPR for a long duration [10.00（1.50, 25.00）min]，had lower body temperature，Glasgow Coma Score，pH and higher blood glucose levels on admission（all P < 0.05）. Conclusion:Drowning is most common in preschool children，common in boys，and drowning prevention measures for young children deserve focused attention. Children found to be in cardiac arrest at the time of drowning have a long duration of drowning and CPR，which predicts a poor neurological prognosis，and timely and effective on-site CPR is the key to reducing the drowning rate.

Objective:To investigate the learning curve for a five-step procedure, namely, a transthoracic single-port assisted laparoscopic transabdominal diaphragmatic approach, for Siewert type II adenocarcinoma of the esophagogastric junction.Methods:In this retrospective cohort study, we analyzed relevant clinical data of 66 patients with Siewert type II adenocarcinoma of the esophagogastric junction who had undergone the five-step procedure performed by the same surgeon in the Gastrointestinal Surgery Department of Guangdong Provincial Hospital of Chinese Medicine from May 2017 to April 2023. The learning curve were plotted using cumulative summation analysis and selected indicators, including intraoperative blood loss, duration of surgery, time to first flatus, time to first tolerance of liquid food, length of hospital stay, and incidence of perioperative complications at different stages were compared. The data were analyzed using SPSS 24.0 statistical software. Numerical data are presented as cases (%) and data were analyzed using the χ 2 test or Fisher's exact test. Normally distributed measurement data are presented as x±s, and independent sample t-testing was performed for inter group comparison. Non-normally distributed measurement data are presented as M( Q1, Q3) and the Mann–Whitney U test was used for inter group comparison. Results:The five-step procedure had been successfully completed without switching to open surgery in all 66 study patients. There were no perioperative deaths, blood loss was 100 (50, 200) mL and duration of surgery 329.4±87.3 minutes. The equation of optimal fit for the duration of surgery was y=0.031x 3-4.4757x 2+164.97x-264.4 ( P<0.001, R2=0.9797). The cumulative summation learning curve reached a vertex when 25 surgical procedures had accumulated. Using 25 cases as the cut-off, we divided the learning curves into learning and proficiency periods and patients into learning (25) and proficiency period groups (41). There were no statistically significant differences between the two groups of patients in sex, age, body mass index, American Society of Anesthesiologists score, history of abdominal surgery, comorbidities, preoperative neoadjuvant therapy, maximum tumor diameter, surgical procedure, or T and N stage of tumor ( P>0.05). The following factors differed significantly (all P<0.05) between the learning and proficiency stages: in the latter there was less intraoperative blood loss (100 [50, 100] ml vs. 200 [100, 200] ml, U=-3.940, P<0.001), shorter duration of surgery ([289.8±50.7] minutes vs. [394.4±96.0] minutes, t=5.034, P<0.001), more mediastinal lymph nodes removed (5 [2, 8] vs. 2 [1, 5], U=-2.518, P=0.012), earlier time to first flatus (2 [2, 3] days vs. 4 [3, 6] days, U=-4.016, P<0.001), earlier time to first tolerance of liquid food (5 [4, 6] days vs. 7 [6, 8] days, U=-2.922, P=0.003), shorter duration of hospital stay (8 [8, 10] vs. 10 [9, 12] days, U=-2.028, P=0.043). The incidence of surgical complications did not differ significantly between the two groups ( P=0.238). Conclusion:Satisfactory results can be achieved with the five-step procedure for patients with Siewert type II adenocarcinoma of the esophagogastric junction once 25 procedures have been performed.

OBJECTIVE To evaluate the therapeutic efficacy and safety of vonoprazan-based triple therapy in treatment-naive patients with Helicobacter pylori （Hp） infection. METHODS From March 2022 to August 2023， 198 treatment-naive patients with Hp infection treated at the outpatient service of department of gastroenterology in our hospital were assigned to the vonoprazan- based triple therapy group （VAC group， n＝98） and the bismuth-based quadruple therapy group （BQT group， n＝100） using the random number table method. Patients in VAC group were given Vonoprazan fumarate tablets （20 mg） + Amoxicillin capsules （1 g） + Clarithromycin tablets （0.5 g）， all twice daily. Patients in BQT group were given Esomeprazole magnesium enteric-coated tablets （20 mg， twice daily） + Metronidazole tablets （0.4 g， four times daily） + Tetracycline tablets （0.5 g， three times daily） + Bismuth potassium citrate capsules （0.6 g， twice daily）. The treatment course for both groups was 14 days. The Hp eradication rates were compared between the two groups in intention-to-treat （ITT）， modified intention-to-treat （MITT）， and per-protocol （PP） analysis sets， while adverse reaction occurrence and medication compliance of two groups were recorded. RESULTS In the ITT， MITT and PP analyses sets， the Hp eradication rates in VAC group were non-inferior to those in BQT group. The incidences of grades 1-2 nausea， vomiting， and loss of appetite in VAC group were significantly lower than in BQT group， and the proportion of patients with good compliance was significantly higher in VAC group （P＜0.05）. Regardless of whether the body mass index （BMI） ≤25 kg/m2 or ＞25 kg/m2， no statistically significant difference was observed in the Hp eradication rates between the two groups （P＞0.05）. CONCLUSIONS Vonoprazan-based triple therapy is non-inferior to bismuth-based quadruple therapy in the treatment of treatment-naive patients with Hp infection， with higher safety and good patient medication compliance. BMI has no significant impact on the Hp eradication rate.

Objective In this study,Knoevenagel derivatives of curcumin were synthesized,and their oil-water partition coefficient were determined.Our aim is to provide an experimental basis for further development of curcumin derivatives.Methods Two Knoevenagel derivatives of curcumin,including 4-(thiophen-2-ylidene)curcumin(3a)and 4-(pyridine-4-ylidene)curcumin(3b),were obtained by using the methylene group of curcumin as the modification site and purified by column chromatography.The structures of these derivatives were confirmed by nuclear magnetic resonance spectroscopy(NMR),infrared(IR)and high-resolution liquid mass spectrometry(HRLC-MS).The oil-water partition coefficient of the derivatives in n-octanol aqueous solution was determined by quantitative analysis using HPLC.Results Knoevenagel derivatives of curcumin were successfully synthesis.The oil-water partition coefficients(lgPap)of curcumin derivatives 3a and 3b are 0.96 and 0.82,respectively.Compared with the oil-water partition coefficient of curcumin(lgPap=3.85),it suggested that curcumin derivatives showed better water solubility than curcumin.Conclusion Compared to the curcumin prototype,Knoevenagel derivatives of curcumin increased water solubility and improved bioavailability.Thus,it may provide experimental basis for introducing heteroarylene moiety of the methylene position of curcumin to enhance pharmacological activity.

Objective To explore the current status of H.pylori infection in the natural population of Sanya City,analyze its influencing factors,and provide a reference basis for the prevention and control of H.pylori infection.Methods A total of 677 residents from four districts of Sanya City were selected by overall stratified random sampling method,and were subjected to urea 14C breath test and questionnaire survey to calculate the positive rate of H.pylori in the natural population and analyze the influencing factors of H.pylori infection.Results A total of 606 residents were included,and the number of H.pylori positive detections was 261,with a positive detection rate of 38.5％.Among them,different ethnicity,marital status,smoking,eating vegetables and fruits,and literacy level were associated with H.pylori infection(P＜0.05);gender,age,BMI,alcohol consumption,drinking water source,betel quid chewing,and the number of cohabitants were not significantly associated with H.pylori infection(P＞0.05).Family infection was an independent risk factor for H.pylori infection in the natural population of Sanya City,and Li ethnicity,frequent consumption of fruits and vegetables,and college and higher education level were independent protective factors for H.pylori infection in the natural population of Sanya City.Conclusion The rate of H.pylori infection in the natural population of Sanya City is lower than the national average.Consuming more fruits and vegetables and improving the awareness of hygiene protection are conducive to the prevention of H.pylori infection;and the promotion of the family and related members with the same examination and treatment is important to avoid aggregation of infection within the family.

RNA editing, an essential post-transcriptional reaction occurring in double-stranded RNA (dsRNA), generates informational diversity in the transcriptome and proteome. In mammals, the main type of RNA editing is the conversion of adenosine to inosine (A-to-I), processed by adenosine deaminases acting on the RNAs (ADARs) family, and interpreted as guanosine during nucleotide base-pairing. It has been reported that millions of nucleotide sites in human transcriptome undergo A-to-I editing events, catalyzed by the primarily responsible enzyme, ADAR1. In hematological malignancies including myeloid/lymphocytic leukemia and multiple myeloma, dysregulation of ADAR1 directly impacts the A-to-I editing states occurring in coding regions, non-coding regions, and immature miRNA precursors. Subsequently, aberrant A-to-I editing states result in altered molecular events, such as protein-coding sequence changes, intron retention, alternative splicing, and miRNA biogenesis inhibition. As a vital factor of the generation and stemness maintenance in leukemia stem cells (LSCs), disordered RNA editing drives the chaos of molecular regulatory network and ultimately promotes the cell proliferation, apoptosis inhibition and drug resistance. At present, novel drugs designed to target RNA editing(e.g., rebecsinib) are under development and have achieved outstanding results in animal experiments. Compared with traditional antitumor drugs, epigenetic antitumor drugs are expected to overcome the shackle of drug resistance and recurrence in hematological malignancies, and provide new treatment options for patients. This review summarized the recent advances in the regulation mechanism of ADAR1-mediated RNA editing events in hematologic malignancies, and further discussed the medical potential and clinical application of ADAR1.