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 explore the application of plasma 7 microRNA (miR7) testing in the differential diagnosis of very early-stage hepatocellular carcinoma (HCC). Methods This study is a multicenter real-world study. Patients with single hepatic lesion (maximum diameter≤2 cm) who underwent plasma miR7 testing at Zhongshan Hospital, Fudan University, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Anhui Provincial Hospital, and Peking University People’s Hospital between January 2019 and December 2024 were retrospectively enrolled. Patients were divided into very early-stage HCC group and non-HCC group, and the clinical pathological characteristics of the two groups were compared. The value of plasma miR7 levels, alpha-fetoprotein (AFP), and des-gamma-carboxy prothrombin (DCP) in the differential diagnosis of very early-stage HCC was evaluated using receiver operating characteristic (ROC) curves and area under the curve (AUC). In patients with both negative AFP and DCP (AFP＜20 ng/mL, DCP＜40 mAU/mL), the diagnostic value of plasma miR7 for very early-stage HCC was analyzed. Results A total of 64 528 patients from 4 hospitals underwent miR7 testing, and 1 682 were finally included, of which 1 073 were diagnosed with very early-stage HCC and 609 were diagnosed with non-HCC. The positive rate of miR7 in HCC patients was significantly higher than that in non-HCC patients (67.9% vs 24.3%, P＜0.001). ROC curves showed that the AUCs for miR7, AFP, and DCP in distinguishing HCC patients from the non-HCC individuals were 0.718, 0.682, and 0.642, respectively. The sensitivities were 67.85%, 43.71%, and 44.45%, and the specificities were 75.70%, 92.78%, and 83.91%, respectively. The pairwise comparison of AUCs showed that the diagnostic efficacy of plasma miR7 detection was significantly better than that of AFP or DCP (P＜0.05). Although its specificity was slightly lower than AFP and DCP, the sensitivity was significantly higher. Among patients negative for both AFP and DCP, miR7 maintained an AUC of 0.728 for diagnosing very early-stage HCC, with 67.82% sensitivity and 77.73% specificity. Conclusions Plasma miR7 testing is a potential molecular marker with high sensitivity and specificity for the differential diagnosis of small hepatic nodules. In patients with very early-stage HCC lacking effective molecular markers (negative for both AFP and DCP), miR7 can serve as a novel and effective molecular marker to assist diagnosis.

Objective: To investigate the indoor fine particulate matter (PM 2.5 ) pollution and its influencing factors in children s bedrooms using solid fuel, so as to provide evidence for effective strategy to reduce PM 2.5 pollution. Methods: From December 2019 to November 2020, 198 households (108 in the north, 90 in the south) from two pilots in the north(Jiamusi in Heilongjiang Province) and south of China (Mianyang in Sichuan Province) were selected, and status of solid fuels using were obtained through home visits, dynamic changes in PM 2.5 concentrations in children s bedrooms were monitored by using real time online instruments, and the influencing factors of PM 2.5 pollution were analyzed by using a mixed effects model. Results: During the monitoring period, the daily PM 2.5 concentrations in the northern and southern pilot were 78.33 (40.50, 154.80) and 38.54(26.20, 58.46) μg/m 3, respectively, exceeding standard rates of 44.57% and 33.22%. During the heating period, the daily PM 2.5 concentrations in the northern and southern pilot were 212.50(133.60,244.10) and 104.42(73.97, 134.90) μg/m 3, respectively, with over standard rates of 96.75% and 86.96%. The mixed effects model analysis results showed that children s bedroom PM 2.5 concentrations were associated with solid fuel usage duration, window opening time, room layout (shared entrance door between kitchen and bedroom), indoor smoking, indoor humidity, and solid fuel use in the bedroom ( β =0.19, -0.05, 1.20, 0.43, 0.02, 0.35, all P <0.05). Conclusion Solid fuel combustion significantly comtributes to PM 2.5 pollution in children s bedrooms, with more pronounced impacts observed in northern China compared to southern regions.

This study aimed to comprehensively examine the association of gallstones, cholecystectomy, and cancer risk. Multivariable logistic regressions were performed to estimate the observational associations of gallstones and cholecystectomy with cancer risk, using data from a nationwide cohort involving 239 799 participants. General and gender-specific two-sample Mendelian randomization (MR) analysis was further conducted to assess the causalities of the observed associations. Observationally, a history of gallstones without cholecystectomy was associated with a high risk of stomach cancer (adjusted odds ratio (aOR)=2.54, 95% confidence interval (CI) 1.50-4.28), liver and bile duct cancer (aOR=2.46, 95% CI 1.17-5.16), kidney cancer (aOR=2.04, 95% CI 1.05-3.94), and bladder cancer (aOR=2.23, 95% CI 1.01-5.13) in the general population, as well as cervical cancer (aOR=1.69, 95% CI 1.12-2.56) in women. Moreover, cholecystectomy was associated with high odds of stomach cancer (aOR=2.41, 95% CI 1.29-4.49), colorectal cancer (aOR=1.83, 95% CI 1.18-2.85), and cancer of liver and bile duct (aOR=2.58, 95% CI 1.11-6.02). MR analysis only supported the causal effect of gallstones on stomach, liver and bile duct, kidney, and bladder cancer. This study added evidence to the causal effect of gallstones on stomach, liver and bile duct, kidney, and bladder cancer, highlighting the importance of cancer screening in individuals with gallstones.
Humans ; Mendelian Randomization Analysis ; Gallstones/complications* ; Female ; Male ; Cholecystectomy/statistics & numerical data* ; Middle Aged ; Risk Factors ; Aged ; Adult ; Neoplasms/etiology* ; Stomach Neoplasms/epidemiology*

Purpose: Vaccinia virus is widely used as an oncolytic agent for human cancer therapy, and several versions of vaccinia virus have demonstrated robust antitumor effects in breast cancer. Most vaccinia viruses are modified by thymidine kinase (TK) deletion. The function of the cyclin-dependent kinase inhibitor p21 in breast cancer remains controversial. We explored the impact of p21 gene knockdown (KD) on breast cancer cells and whether p21 KD interferes with the antitumor effect of TK-negative vaccinia virus. Methods: p21 KD MDA-MB-231 and p21 KD MCF-7 cells were prepared, and cell proliferation and migration rates were evaluated using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and scratch healing assays. The tumor growth of xenografts originating from p21KD MDA-MB-231 cells and control cells was compared in a mouse model. The colony formation and sphere-forming abilities of p21 KD breast cancer cells were also determined using low-melting agarose and serum-free culture. The tumorkilling effect of the vaccinia virus was determined in breast cancer cells and mouse models using an MTT assay and tumor cell xenografts. Results: p21 KD increased the growth and migration of MDA-MB-231 and MCF-7 cells and promoted the cell growth of MDA-MB-231 cells in mice, while decreasing the colony formation and sphere formation abilities. Expression of TK was reduced in p21 KD MDAMB-231 cells. Oncolytic effects of both wild-type and TK-deleted vaccinia viruses were attenuated in p21KD MDA-MB-231 cells. The tumor-killing effect of TK-deleted vaccinia virus was also weakened in xenografted mice bearing p21 KD MDA-MB-231 cells. Conclusion Targeted inhibition of p21 accelerates the proliferation and migration of breast cancer cells and impairs the tumor-killing effect of vaccinia virus, suggesting that p21 levels in cancer cells interfere with vaccinia virus oncolytic therapy.

Objective:To study the overall training effect of segmented training model on key fiberoptic bronchoscopy techniques for anesthesiology residents and the influence of key technique training order on the training effect.Methods:Different fiberoptic bronchoscopy simulators were used for specialized training in different key techniques of fiberoptic operation. To examine the effect of key technique learning order on the teaching effect, 40 anesthesiology residents who participated in fiberscope simulation training at Ruijin Hospital, Shanghai Jiaotong University School of Medicine between November 2022 and March 2023 were selected for this study. They were randomly divided into two groups (Group S and Group M) using a numerical table method. The teaching was completed using two orders of key techniques. The operation time, operation quality score, and theoretical knowledge mastery score of the two groups were recorded to compare the effect of key technique learning order on the mastery of fiberoptic skills. SPSS 29.0 statistical software was used for data analysis. Measurement data that conformed to normal distribution were expressed as mean ± standard deviation, and the independent samples t-test or Fisher's exact test were used for comparison between groups. The chi-square test was used for comparison of enumeration data. Results:After segmented training in each key technique, both groups of trainees were able to shorten the operation time of the corresponding key technique [SM simulator operation time (132.25±14.69) s vs. (49.80±4.46) s in group S, P<0.01; M simulator operation time (82.30±11.60) s vs. (57.10±6.77) s in group S, P<0.01; SM simulator operation time (83.10±10.62) s vs. (52.10±5.20) s in group M, P<0.01; M simulator operation time (132.25±14.69) s vs. (55.40±5.91) s in group M, P<0.01)]. Moreover, both groups showed a reduced number of wall touches [SM simulator wall touches (3.35±0.93) times vs. (0.65±0.49) times in group S, P<0.01; M simulator wall touches (2.50±1.05) times vs. (0.70±0.80) times in group S, P<0.01; SM simulator wall touches (1.55±1.15) times vs. (0.40±0.50) times in group M, P<0.01; M simulator wall touches (5.90±1.29) times vs. (1.10±0.79) times in group M, P<0.01]. There were no significant differences between the two groups in the performance score of fiberoptic-guided tracheal intubation after training [(92.50±5.97) points vs. (91.75±5.45) points] and in the lung segment localization time [(23.15±4.39) s, (21.40±4.84) s, (22.85±4.42) s vs. (22.75±5.11) s, (21.00±5.40) s, (21.50±5.10) s]. Conclusions:Segmented training on key fiberoptic bronchoscopy techniques is an effective model of fiberscope training for anesthesiology residents, and the order of training key techniques does not affect the effectiveness of training.

Purpose: Vaccinia virus is widely used as an oncolytic agent for human cancer therapy, and several versions of vaccinia virus have demonstrated robust antitumor effects in breast cancer. Most vaccinia viruses are modified by thymidine kinase (TK) deletion. The function of the cyclin-dependent kinase inhibitor p21 in breast cancer remains controversial. We explored the impact of p21 gene knockdown (KD) on breast cancer cells and whether p21 KD interferes with the antitumor effect of TK-negative vaccinia virus. Methods: p21 KD MDA-MB-231 and p21 KD MCF-7 cells were prepared, and cell proliferation and migration rates were evaluated using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and scratch healing assays. The tumor growth of xenografts originating from p21KD MDA-MB-231 cells and control cells was compared in a mouse model. The colony formation and sphere-forming abilities of p21 KD breast cancer cells were also determined using low-melting agarose and serum-free culture. The tumorkilling effect of the vaccinia virus was determined in breast cancer cells and mouse models using an MTT assay and tumor cell xenografts. Results: p21 KD increased the growth and migration of MDA-MB-231 and MCF-7 cells and promoted the cell growth of MDA-MB-231 cells in mice, while decreasing the colony formation and sphere formation abilities. Expression of TK was reduced in p21 KD MDAMB-231 cells. Oncolytic effects of both wild-type and TK-deleted vaccinia viruses were attenuated in p21KD MDA-MB-231 cells. The tumor-killing effect of TK-deleted vaccinia virus was also weakened in xenografted mice bearing p21 KD MDA-MB-231 cells. Conclusion Targeted inhibition of p21 accelerates the proliferation and migration of breast cancer cells and impairs the tumor-killing effect of vaccinia virus, suggesting that p21 levels in cancer cells interfere with vaccinia virus oncolytic therapy.

Objective To investigate the incidence rate,clinical characteristics,and prognosis of neonatal stroke in Shenzhen,China.Methods Led by Shenzhen Children's Hospital,the Shenzhen Neonatal Data Collaboration Network organized 21 institutions to collect 36 cases of neonatal stroke from January 2020 to December 2022.The incidence,clinical characteristics,treatment,and prognosis of neonatal stroke in Shenzhen were analyzed.Results The incidence rate of neonatal stroke in 21 hospitals from 2020 to 2022 was 1/15 137,1/6 060,and 1/7 704,respectively.Ischemic stroke accounted for 75％(27/36);boys accounted for 64％(23/36).Among the 36 neonates,31(86％)had disease onset within 3 days after birth,and 19(53％)had convulsion as the initial presentation.Cerebral MRI showed that 22 neonates(61％)had left cerebral infarction and 13(36％)had basal ganglia infarction.Magnetic resonance angiography was performed for 12 neonates,among whom 9(75％)had involvement of the middle cerebral artery.Electroencephalography was performed for 29 neonates,with sharp waves in 21 neonates(72％)and seizures in 10 neonates(34％).Symptomatic/supportive treatment varied across different hospitals.Neonatal Behavioral Neurological Assessment was performed for 12 neonates(33％,12/36),with a mean score of(32±4)points.The prognosis of 27 neonates was followed up to around 12 months of age,with 44％(12/27)of the neonates having a good prognosis.Conclusions Ischemic stroke is the main type of neonatal stroke,often with convulsions as the initial presentation,involvement of the middle cerebral artery,sharp waves on electroencephalography,and a relatively low neurodevelopment score.Symptomatic/supportive treatment is the main treatment method,and some neonates tend to have a poor prognosis.

Multiple myeloma(MM)is a malignant disease with abnormal proliferation of clonal plasma cells.The development of the disease shows a vast heterogeneity,which is closely related to the interaction between MM cells and bone marrow microenvironment(BMM).The interleukin-6(IL-6)/interleukin-6 receptor(IL-6R)/Janus kinase 2(JAK2)/signal transducer and activator of transcription 3(STAT3)pathway can regulate the transcription of related soluble factors in BMM,promote the proliferation,anti-apoptosis,drug resistance and guide related bone destruction of MM cells.This article reviews the research progress on the effect of BMM regulated by IL-6/IL-6R/JAK2/STAT3 pathway on the biological behavior of MM,in order to provide new research ideas for targeted therapy and precise therapy of MM.

Objective:To compare the clinical efficacy of axillary transthoracic approach and posterior approach in the treatment of upper thoracic tuberculosis with vertebral clearance, bone graft fusion, and internal fixation surgery.Methods:Fifty five patients with upper thoracic tuberculosis admitted to Changsha Central Hospital, University of South China from March 2017 to March 2022 were selected and divided into axillary transthoracic group and posterior group according to different surgical approaches. The incision length, surgical time, intraoperative blood loss, and postoperative hospitalization time were compared between the two groups of patients. Two groups of patients were recorded for preoperative and postoperative pain visual analog scale (VAS) scores, Oswestry Disability Index (ODI) scores at 1 week, 3 months, and 12 months, preoperative and postoperative serum inflammatory indicators, CD4 + /CD8 + ratio of T lymphocyte subsets, and complications. Results:The incision length, operation time, and intraoperative blood loss in the axillary transthoracic group were significantly less than those in the posterior group, and the differences were statistically significant (all P<0.05). However, there was no statistically significant difference in postoperative hospitalization time between the two groups of patients ( P>0.05). The VAS and ODI scores of the two groups of patients showed significant improvement compared to preoperative levels at 1 week, 3 months, and 12 months after surgery (all P<0.05); And at 1 week and 3 months after surgery, the VAS scores of patients in the axillary transthoracic group were significantly lower than those in the posterior group (all P<0.05), and the ODI scores at 3 and 12 months after surgery were significantly lower than those in the posterior group (all P<0.05). The erythrocyte sedimentation rate and CRP levels of both groups of patients increased significantly one week after surgery compared with preoperative levels (all P<0.05), but the erythrocyte sedimentation rate and CRP levels basically returned to normal levels at three months after surgery. The CD4 + /CD8 + ratio of T lymphocyte subsets in both groups was lower than preoperative levels at one week after surgery, but with the continuation of treatment, the CD4 + /CD8 + ratio increased significantly at three months after surgery. Conclusions:Both axillary and posterior approaches can be used for surgical treatment of upper thoracic tuberculosis, but axillary and thoracic approaches have the advantages of less trauma, less bleeding, and faster recovery.