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 determine whether monotropein has an anticancer effect and explore its potential mechanisms against colorectal cancer (CRC) through network pharmacology and molecular docking combined with experimental verification. METHODS: Network pharmacology and molecular docking were used to predict potential targets of monotropein against CRC. Cell counting kit assay, plate monoclonal assay and microscopic observation were used to investigate the antiproliferative effects of monotropein on CRC cells HCT116, HT29 and LoVo. Flow cytometry and scratch assay were used to analyze apoptosis and cell cycle, as well as cell migration, respectively in HCT116, HT29, and LoVo cells. Western blotting was used to detect the expression of proteins related to apoptosis, cell cycle, and cell migration, and the expression of proteins key to the Akt pathway. RESULTS: The Gene Ontology and Reactome enrichment analyses indicated that the anticancer potential of monotropein against CRC might be involved in multiple cancer-related signaling pathways. Among these pathways, RAC-beta serine/threonine-protein kinase (Akt1, Akt2), cyclin-dependent kinase 6 (CDK6), matrix metalloproteinase-9 (MMP9), epidermal growth factor receptor (EGFR), cell division control protein 42 homolog (CDC42) were shown as the potential anticancer targets of monotropein against CRC. Molecular docking suggested that monotropein may interact with the 6 targets (Akt1, Akt2, CDK6, MMP9, EGFR, CDC42). Subsequently, cell activity of HCT116, HT29 and LoVo cell lines were significantly suppressed by monotropein (P<0.05). Furthermore, our research revealed that monotropein induced cell apoptosis by inhibiting Bcl-2 and increasing Bax, induced G₁-S cycle arrest in colorectal cancer by decreasing the expressions of CyclinD1, CDK4 and CDK6, inhibited cell migration by suppressing the expressions of CDC42 and MMP9 (P<0.05), and might play an anticancer role through Akt signaling pathway. CONCLUSION Monotropein exerts its antitumor effects primarily by arresting the cell cycle, causing cell apoptosis, and inhibiting cell migration. This indicates a high potential for developing novel medication for treating CRC.
Humans ; Proto-Oncogene Proteins c-akt/metabolism* ; Cell Proliferation ; Matrix Metalloproteinase 9 ; Molecular Docking Simulation ; Cell Cycle ; ErbB Receptors ; Apoptosis ; Colorectal Neoplasms/pathology* ; Cell Line, Tumor

Objective:To investigate the impact of daily step count on glycemic outcomes in community residents with impaired glucose tolerance (IGT).Methods:This was a prospective cohort study, in October 2018, 204 residents who met the criteria of IGT were recruited in the Shijingshan District in Beijing. The subjects were tested for fasting blood glucose, oral glucose tolerance test 2-hour blood glucose (2hBG), glycated hemoglobin A 1c (HbA 1c), lipid profile, liver and kidney function, as well as measurements of height, weight and waist circumference. A dedicated mobile application was used to deliver prediabetes health knowledge monthly. Online guidance was provided to answer questions and daily step count was collected using the application. Three years later, a follow-up was conducted to assess the participants′ glycemic outcomes and other indexes, and a total of 142 participants completed the follow-up review. According to daily step count, the subjects were categorized into high step count group (42 cases,>7 000 steps daily), moderate step count group (54 cases, 5 000-7 000 steps daily), and low step count group (46 cases,<5 000 steps daily). Subjects were categorized into diabetes group (30 cases), prediabetes group (77 cases) and normal glucose tolerance group (35 cases) with glycemic outcomes. Independent sample t test was used to compare the differences in blood glucose, blood lipids, and step counts between the two groups. Kruskal-Wallis H test or one-way ANOVA was used to compare the differences in blood glucose, blood lipids, and step counts between multiple groups. The χ2 test was used to compare the differences in glycemic outcomes between multiple groups. Multivariate logistic regression analysis was used to assess the impact of daily step counts and body mass index on glycemic outcomes. Linear regression analysis was used to evaluate the relationship between daily step counts and 2 h BG. Results:A total of 142 participants completed the 3-year follow-up, including 43 males and 99 females, with a mean age of (60.15±5.67) years. At baseline, males had significantly higher body mass index, waist circumference, and fasting blood glucose when compared to those in females [(26.97±2.43) vs (24.89±2.93) kg/m 2, (92.68±7.75) vs (83.83±8.60) cm, (5.83±0.61) vs (5.62±0.52) mmol/L], the total cholesterol and HDL-C were also significantly lower in males than those in females [(5.10±1.16) vs (5.55±0.95) mmol/L, (1.35±0.34) vs (1.56±0.35) mmol/L] (all P<0.05). After 3-year follow-up, 21.1% (30/142) of IGT participants progressed to diabetes, with an annual conversion rate of approximately 7%. The normal glucose tolerance group showed significantly higher daily step counts when compared with the prediabetes and diabetes groups [(7 886±2 867) vs (5 981±2 655) vs (4 117±2 674) steps] ( H=31.778, P<0.001). Individuals with higher daily step counts exhibited lower body mass index, 2 h BG, and HbA 1c level when compared with those in the ones with moderate and low step counts [(24.26±3.09) vs (25.44±3.38) vs (26.26±3.59) kg/m 2, (7.50±1.71) vs (9.15±3.30) vs (11.19±3.84) mmol/L, 5.97%±0.46% vs 6.14%±0.99% vs 6.40%±0.96%] (all P<0.05). Higher step count was positively correlated with the reversal of prediabetes to normal blood glucose levels (moderate step count, OR=0.297, 95% CI: 0.109-0.804; low step count, OR=0.055, 95% CI: 0.010-0.287), lower daily step count correlated positively with prediabetes progressing to diabetes ( OR=4.857, 95% CI: 1.140-20.689) (all P<0.05). For every additional 1 000 steps per day, the 2 h BG decreased by 0.5 mmol/L. Conclusion:As daily step count increases, the glucose metabolism improves in IGT community residents. Higher daily step count is associated with reversal of IGT to normal glucose tolerance, while lower daily step count may be associated with the progression of IGT to diabetes.

Objective:To report the results of national surveillance on the distribution and antimicrobial resistance profile of clinical Gram-negative bacteria isolates from bloodstream infections in China in 2022.Methods:The clinical isolates of Gram-negative bacteria from blood cultures in member hospitals of national bloodstream infection Bacterial Resistant Investigation Collaborative System（BRICS）were collected during January 2022 to December 2022. Antibiotic susceptibility tests were conducted by agar dilution or broth dilution methods recommended by Clinical and Laboratory Standards Institute（CLSI）. WHONET 5.6 and SPSS 25.0 software were used to analyze the data.Results:During the study period，9 035 strains of Gram-negative bacteria were collected from 51 hospitals，of which 7 895（87.4%）were Enterobacteriaceae and 1 140（12.6%）were non-fermenting bacteria. The top 5 bacterial species were Escherichia coli（ n=4 510，49.9%）， Klebsiella pneumoniae（ n=2 340，25.9%）， Pseudomonas aeruginosa（ n=534，5.9%）， Acinetobacter baumannii complex（ n=405，4.5%）and Enterobacter cloacae（ n=327，3.6%）. The ESBLs-producing rates in Escherichia coli， Klebsiella pneumoniae and Proteus spp. were 47.1%（2 095/4 452），21.0%（427/2 033）and 41.1%（58/141），respectively. The prevalence of carbapenem-resistant Escherichia coli（CREC）and carbapenem-resistant Klebsiella pneumoniae（CRKP）were 1.3%（58/4 510）and 13.1%（307/2 340）；62.1%（36/58）and 9.8%（30/307）of CREC and CRKP were resistant to ceftazidime/avibactam combination，respectively. The prevalence of carbapenem-resistant Acinetobacter baumannii（CRAB）complex was 59.5%（241/405），while less than 5% of Acinetobacter baumannii complex was resistant to tigecycline and polymyxin B. The prevalence of carbapenem-resistant Pseudomonas aeruginosa（CRPA）was 18.4%（98/534）. There were differences in the composition ratio of Gram-negative bacteria in bloodstream infections and the prevalence of main Gram-negative bacteria resistance among different regions，with statistically significant differences in the prevalence of CRKP and CRPA（ χ2=20.489 and 20.252， P<0.001）. The prevalence of CREC，CRKP，CRPA，CRAB，ESBLs-producing Escherichia coli and Klebsiella pneumoniae were higher in provinicial hospitals than those in municipal hospitals（ χ2=11.953，81.183，10.404，5.915，12.415 and 6.459， P<0.01 or <0.05），while the prevalence of CRPA was higher in economically developed regions（per capita GDP ≥ 92 059 Yuan）than that in economically less-developed regions（per capita GDP <92 059 Yuan）（ χ2=6.240， P=0.012）. Conclusions:The proportion of Gram-negative bacteria in bloodstream infections shows an increasing trend，and Escherichia coli is ranked in the top，while the trend of CRKP decreases continuously with time. Decreasing trends are noted in ESBLs-producing Escherichia coli and Klebsiella pneumoniae. Low prevalence of carbapenem resistance in Escherichia coli and high prevalence in CRAB complex have been observed. The composition ratio and antibacterial spectrum of bloodstream infections in different regions of China are slightly different，and the proportion of main drug resistant bacteria in provincial hospitals is higher than those in municipal hospitals.

Objective:To compare the efficacy of fractional CO 2 laser combined with topical delivery of fluorouracil versus compound betamethasone injections in the treatment of vitiligo. Methods:Clinical data were collected from 94 patients with localized, non-segmental, and stable vitiligo, who received fractional CO 2 laser combined with drug delivery at the Cosmetological Center, Xijing Hospital, Air Force Medical University from October 2018 to May 2023, and were retrospectively analyzed. Among them, there were 40 cases in the fractional CO 2 laser combined with fluorouracil injection group, and 54 cases in the fractional CO 2 laser combined with compound betamethasone injection group. All the patients received the above treatment once a month for 5 sessions. A 4-level grading scale was used to evaluate the pigmentation improvement, and the clinical efficacy and safety of the two therapeutic regimens were compared. Comparisons between groups were performed using chi-square test, Fisher′s exact test, and t test. Results:In the fractional CO 2 laser combined with fluorouracil injection group, there were 22 males and 18 females, their ages were 21.95 ± 12.88 years, and the disease duration was 25.46 ± 11.42 months; in the fractional CO 2 laser combined with compound betamethasone injection group, there were 36 males and 18 females, their ages were 22.26 ± 8.79 years, and the disease duration was 26.51 ± 12.81 months. One month after the first treatment, no significant difference was observed in the efficacy between the two groups ( χ2 = 1.39, P = 0.238). One month after the fifth treatment, 2 (5.0%) patients showed an excellent response, 4 (10.0%) showed a good response, 12 (30.0%) showed a mild response, and 22 (55.0%) showed a poor response in the fractional CO 2 laser combined with fluorouracil injection group; in the fractional CO 2 laser combined with compound betamethasone injection group, 8 (14.8%) patients showed a good response, 8 (14.8%) showed a mild response, and 38 (70.4%) showed a poor response; there was no significant difference in the efficacy between the two groups after 5 sessions of treatment ( χ2 = 2.35, P = 0.125). After either 1 or 5 sessions of treatment, there were no significant differences in the efficacy for lesions on the face and neck, trunk and limbs, hands and feet between the two therapeutic regimens (all P > 0.05). Comparisons of the efficacy for skin lesions on different body sites showed that one session of the fractional CO 2 laser combined with fluorouracil injection was more effective for the treatment of skin lesions on the face and neck compared with those on the hands and feet ( P = 0.039) ; after 5 sessions of treatment, the two therapeutic regimens both showed better efficacy for facial skin lesions compared with hand and foot skin lesions ( P = 0.005, 0.049). There was no significant difference in the occurrence of adverse reactions such as pigmentation, infection and scarring between the two groups. Conclusion:The fractional CO 2 laser combined with topical delivery of fluorouracil and compound betamethasone injections showed similar efficacy and safety in the treatment of vitiligo, and both can be used as treatment options for vitiligo.

Objective:To investigate the mechanism of inhibiting inflammatory response by negative pressure wound therapy in the chronic venous leg ulcer.Method:The clinical data of 29 patients with chronic VLU treated in Hechuan-Rhine Traditional Chinese Medicine Hospital of Shanghai from June 2018 to December 2021 were collected.According to different treatment meth-ods,the patients were divided into the control group(n=13)and the observation group(n=16).The control group adopted routine varicose vein operations and debridement,routine dressing change was performed on the VLU wound every other day after operation.The observation group adopted debridement and then NPWT on the basis of routine varicose vein operations,the VLU wound was continuously drained with negative pressure for 1 week after operation.IL-1β and IL-18 levels were measured with ELISA.ASC、NLRP3 and Caspase-1 levels were detected with Western blot-ting.The autologous skin transplantation time of the two groups were calculated by survival curve analysis.Results:The inflammatory response was milder in the observation group than in the con-trol group 7 days after operation.The results of ELISA showed that the levels of IL-1 p and IL-18 in the observation group were lower than those in the control group.The results of Western blotting showed that the relative expression levels of ASC、NLRP3 and Caspase-1 in the observation group were lower than those in the control group.The survival curve analysis showed that the autologous skin transplantation time of the observation group was less than the control group.Conclusion:The inflammatory response can be distinctly alleviated by NPWT in the VLU,leading to better condi-tions for autologous skin transplantation within a short period.

Osteoporotic proximal humeral fracture (OPHF) is one of the common osteoporotic fractures in the aged, with an incidence only lower than vertebral compression fracture, hip fracture, and distal radius fracture. OPHF, secondary to osteoporosis and characterized by poor bone quality, comminuted fracture pattern, slow healing, and severely impaired shoulder joint function, poses a big challenge to the current clinical diagnosis and treatment. In the field of diagnosis, treatment, and rehabilitation of OPHF, traditional Chinese and Western medicine have accumulated rich experience and evidence from evidence-based medicine and achieved favorable outcomes. However, there is still a lack of guidance from a relevant consensus as to how to integrate the advantages of the two medical systems and achieve the integrated diagnosis and treatment. To promote the diagnosis and treatment of OPHF with integrated traditional Chinese and Western medicine, relevant experts from Orthopedic Expert Committee of Geriatric Branch of Chinese Association of Gerontology and Geriatrics, Youth Osteoporosis Group of Orthopedic Branch of Chinese Medical Association, Osteoporosis Group of Orthopedic Surgeon Branch of Chinese Medical Doctor Association, and Osteoporosis Committee of Shanghai Association of Integrated Traditional Chinese and Western Medicine have been organized to formulate Expert consensus on the diagnosis and treatment of osteoporotic proximal humeral fracture with integrated traditional Chinese and Western medicine ( version 2024) by searching related literatures and based on the evidences from evidence-based medicine. This consensus consists of 13 recommendations about the diagnosis, treatment and rehabilitation of OPHF with integrated traditional Chinese medicine and Western medicine, aimed at standardizing, systematizing, and personalizing the diagnosis and treatment of OPHF with integrated traditional Chinse and Western medicine to improve the patients ′ function.

This study aimed to investigate the role and mechanism of sappanone A (SA) in regulating renal ischemia-reperfusion injury (IRI) in rats. The animal experiment has been approved by the Ethics Committee of Suzhou Wujiang District Children's Hospital (approval number: 2022010). First, hematoxylin-eosin (H&E) staining was used to evaluate the effects of SA on IRI, and renal damage was scored. Serum creatinine (SCr), blood urea nitrogen (BUN) and cystatin C (Cystatin C) were analyzed. The effect of sappanone A on the apoptosis of renal tubular epithelial cells induced by IRI was analyzed by TUNEL staining. Protein expression levels of p-JNK/JNK, p-ERK/ERK, Bcl2, Bax and cleaved-caspase 3 in renal tissues were detected by Western blot. Finally, H&E staining, serological analysis, TUNEL staining and Western blot were used to determine whether JNK activator anisomycin could reverse the effect of SA on IRI in rats. The results showed SA significantly reduced the renal tubule injury caused by ischemia-reperfusion, and decreased the level of SCr, BUN and Cys C in serum. TUNEL staining showed that SA significantly reduced the apoptosis of renal tubular epithelial cells induced by IRI. Western blot analysis of kidney tissue showed that SA significantly promoted the expression of apoptosis inhibiting protein Bcl2 and inhibited the expression of apoptosis-promoting proteins Bax and cleaved-caspase 3. Further analysis elucidated that SA did not affect the phosphorylation of ERK but decreased the phosphorylation of JNK. Finally, H&E staining, serological analysis, TUNEL staining and Western blot confirmed that JNK activator anisomycin could reverse the alleviating effect of SA on IRI in rats. The above findings suggest that SA could alleviate IRI in rats by inhibiting JNK phosphorylation.

ObjectiveTo observe the efficacy and safety of Uyghur medicine Yangxin Dawayimixike Honey Paste （养心达瓦依米西克蜜膏， YDMHP） in the treatment of stable angina pectoris （SAP） of qi stagnation and blood stasis syndrome. MethodsA randomized ， double-blind， positive-controlled，multi-center clinical trial was conducted， in which 370 patients with SAP of qi stagnation and blood stasis syndrome were randomly divided into treatment group（279 cases）and control group（91cases）at a ratio of 3∶1. The treatment group was orally administered with YDMHP， 3 g each time， and placebo of Xuefu Zhuyu Capsule （血府逐瘀胶囊）， 2.4 g each time， while the control group was treated with Xuefu Zhuyu Capsule， 2.4 g each time， and placebo of YDMHP， 3 g each time， both twice a day for a course of 12 weeks. The primary outcome was the effect of angina pectoris symptom. The secondary outcomes include single angina symptom scores such as number of attacks， duration of attacks， pain intensity and usae of nitroglycerin scores， the total angina symptom score before and after the treatment， the usage of nitroglycerin， the exercise duration in treadmill exercise test （TET） and the Duck treadmill score among patients，the scores of Seattle Angina Questionnaire （SAQ） on five dimensions including physical limitations， anginal stability， anginal frequency， treatment satisfaction， and disease perception， and efficacy of TCM syndrome and of each single TCM symptom after treatment. The safety were evaluated by examine blood routine， urine routine， liver and kidney function， fasting blood sugar， electrocardiogram， adverse events. ResultsThe total effective rate of angina symptom in the treatment group was 71.69% （200/279）， significantly higher than 51.64% （47/91） in the control group （P＜0.01）. The curative and markedly effective rate of TCM syndrome in the treatment group was 53.05% （148/279）， which was significantly higher than 25.27% （23/91） in the control group （P＜0.01）. After treatment， scores of the number as well as duration of angina attacks and pain severity， the total score of angina symptoms， and the usage of nitroglycerin significantly decreased in both groups， and more changes were seen in the treatment group than in the control group； the scores of physical limitations， anginal stability， anginal frequency， treatment satisfaction， and disease perception in both groups significantly increased， and more improvement were shown in the experimental group regarding the anginal stability， anginal frequency and treatment satisfaction （P＜0.05 or P＜0.01）. The effects of chest pain， chest tightness， palpitation， shortness of breath and fatigue in experimental group were significantly higher than those in control group （P＜0.05 or P＜0.01）. There was no significant difference in the exercise duration of treadmill test and Duke score among patients between the two groups either before or after treatment （P＞0.05）. Adverse events occurred in 66 cases （23.66%） of the experimental group and 16 cases （17.58%） of the control group， with no statistical significance between the two groups （P＞0.05）. ConclusionThe Uyghur medicine YDMHP can effectively improve symptoms of angina pectoris， reduce the number， duration， and intensity of attacks， decrease the dosage of nitrogly-cerin and improve the individual TCM symptoms and has good safety in the treatment of SAP patients of qi stagnation and blood stasis.

Objective:To report the results of national surveillance on the distribution and antimicrobial resistance profile of clinical Gram-positive bacteria isolates from bloodstream infections in China in 2022.Methods:The clinical isolates of Gram-positive bacteria from blood cultures in member hospitals of National Bloodstream Infection Bacterial Resistant Investigation Collaborative System（BRICS）were collected during January 2022 to December 2022. Antibiotic susceptibility tests were conducted by agar dilution or broth dilution methods recommended by Clinical and Laboratory Standards Institute（CLSI）. WHONET 5.6 and SPSS 25.0 software were used to analyze the data.Results:A total of 3 163 strains of Gram-positive pathogens were collected from 51 member units，and the top five bacteria were Staphylococcus aureus（ n=1 147，36.3%），coagulase-negative Staphylococci（ n=928，29.3%）， Enterococcus faecalis（ n=369，11.7%）， Enterococcus faecium（ n=296，9.4%）and alpha-hemolyticus Streptococci（ n=192，6.1%）. The detection rates of methicillin-resistant Staphylococcus aureus（MRSA）and methicillin-resistant coagulase-negative Staphylococci（MRCNS）were 26.4%（303/1 147）and 66.7%（619/928），respectively. No glycopeptide and daptomycin-resistant Staphylococci were detected. The sensitivity rates of Staphylococcus aureus to cefpirome，rifampin，compound sulfamethoxazole，linezolid，minocycline and tigecycline were all >95.0%. Enterococcus faecium was more prevalent than Enterococcus faecalis. The resistance rates of Enterococcus faecium to vancomycin and teicoplanin were both 0.5%（2/369），and no vancomycin-resistant Enterococcus faecium was detected. The detection rate of MRSA in southern China was significantly lower than that in other regions（ χ2=14.578， P=0.002），while the detection rate of MRCNS in northern China was significantly higher than that in other regions（ χ2=15.195， P=0.002）. The detection rates of MRSA and MRCNS in provincial hospitals were higher than those in municipal hospitals（ χ2=13.519 and 12.136， P<0.001）. The detection rates of MRSA and MRCNS in economically more advanced regions（per capita GDP≥92 059 Yuan in 2022）were higher than those in economically less advanced regions（per capita GDP<92 059 Yuan）（ χ2=9.969 and 7.606， P=0.002和0.006）. Conclusions:Among the Gram-positive pathogens causing bloodstream infections in China， Staphylococci is the most common while the MRSA incidence decreases continuously with time；the detection rate of Enterococcus faecium exceeds that of Enterococcus faecalis. The overall prevalence of vancomycin-resistant Enterococci is still at a low level. The composition ratio of Gram-positive pathogens and resistant profiles varies slightly across regions of China，with the prevalence of MRSA and MRCNS being more pronounced in provincial hospitals and areas with a per capita GDP≥92 059 yuan.