Objective To explore the adverse event signals of children using macrolide drugs （azithromycin, clarithromycin, and erythromycin）, and provide reference for rational medicine use in clinical practice. Methods Data from children under 12 years old were extracted from the US FAERS database spanning from the first quarter of 2004 to the second quarter of 2023. The adverse drug reaction （ADR） signal mining for three macrolide antibiotics was conducted using the Reporting Odds Ratio （ROR） and Bayesian Confidence Propagation Neural Network （BCPNN） methods. Special emphasis was placed on analyzing and contrasting the differences in adverse events among the three drugs. Results A total of 1 615 reports for children under 12 years old were retrieved from the FAERS database, including 1 024 reports of azithromycin, 460 reports of clarithromycin, and 131 reports of erythromycin. Among azithromycin and erythromycin, there were more reports from boys than girls, while for clarithromycin, there were more reports from girls than boys. Oral administration was the most common route of administration for all three drugs. Regarding the outcome of adverse events reported, azithromycin and clarithromycin were primarily associated with other serious adverse events, whereas erythromycin was mainly associated with hospitalization and other serious adverse events. The number of adverse events reported decreased with increasing age, with a higher number of reports in the 0-3 age group. Using the ROR and BCPNN methods for signal detection, 86 signals were identified for azithromycin, 91 for clarithromycin, and 34 for erythromycin. These signals involved 22 System Organ Classes （SOCs）, with azithromycin mainly concentrated in skin and subcutaneous tissue disorders （n=21）, clarithromycin in gastrointestinal disorders （n=15）, and erythromycin in gastrointestinal disorders （n=8）. Twenty-four signals of moderate to high risk were detected, with 13 for azithromycin, 9 for clarithromycin, and 2 for erythromycin. Conclusion The adverse events induced by the three drugs with different risks in different systems. When clinically treating Mycoplasma pneumoniae pneumonia in children, the risk profiles of drugs in different systems should be considered, and personalized dosing should be implemented.

Bone is a highly calcified and vascularized tissue. The vascular system plays a vital role in supporting bone growth and repair, such as the provision of nutrients, growth factors, and metabolic waste transfer. Moreover, the additional functions of the bone vasculature, such as the secretion of various factors and the regulation of bone-related signaling pathways, are essential for maintaining bone health. In the bone microenvironment, bone tissue cells play a critical role in regulating angiogenesis, including osteoblasts, bone marrow mesenchymal stem cells (BMSCs), and osteoclasts. Osteogenesis and bone angiogenesis are closely linked. The decrease in osteogenesis and bone angiogenesis caused by aging leads to osteoporosis. Long noncoding RNAs (lncRNAs) are involved in various physiological processes, including osteogenesis and angiogenesis. Recent studies have shown that lncRNAs could mediate the crosstalk between angiogenesis and osteogenesis. However, the mechanism by which lncRNAs regulate angiogenesis‒osteogenesis crosstalk remains unclear. In this review, we describe in detail the ways in which lncRNAs regulate the crosstalk between osteogenesis and angiogenesis to promote bone health, aiming to provide new directions for the study of the mechanism by which lncRNAs regulate bone metabolism.
RNA, Long Noncoding/physiology* ; Osteogenesis/physiology* ; Humans ; Neovascularization, Physiologic/genetics* ; Bone and Bones/metabolism* ; Animals ; Mesenchymal Stem Cells ; Signal Transduction ; Osteoblasts ; Osteoclasts ; Angiogenesis

Objective: To analyze the association of participation in non-sports extracurricular tutoring classes with the prevalence of screening myopia, axial length (AL) and axial length to corneal radius ratio (AL/CR) among primary school students, so as to provide evidences for formulating myopia prevention and control policies. Methods: In December 2024, combination of convenience and cluster sampling method was used to select 2 273 students from two primary schools in Hefei City, Anhui Province. Ophthalmic examinations and questionnaire surveys were conducted to obtain information on myopia, AL, AL/CR and participation in various types of extracurricular tutoring. A binary Logistic regression model was used to analyze the association between non-sports tutoring and screening myopia, and multiple linear regression models were used to examine the associations between non-sports tutoring and AL and AL/CR. Results: Among the surveyed students, the participation rate in non-sports extracurricular tutoring classes was 64.9% , and the overall prevalence of screening myopia was 39.1%. The average AL and AL/CR were (23.60± 1.01 ) mm and (3.00±0.12), respectively. Univariate analysis showed that students who attended non-sports, music, or academic tutoring classes for ≥2 h per week had higher risks of screening myopia and greater AL/CR values than non-participants (screening myopia: OR =1.38, 1.82, 1.55; AL/CR: β =0.01, 0.03, 0.03; all P <0.05). After adjusting for sex, grade, and participation in sports tutoring, multivariate analysis indicated that participation in non-sports and musical instrument tutoring classes for ≥2 h per week remained significantly associated with higher risks of screening myopia ( OR =1.26, 1.49, both P <0.05). Multiple linear regression showed that participation in musical instrument tutoring for ≥2 h per week was positively correlated with AL ( β=0.14, P < 0.05). Conclusions Participation in non-sports extracurricular tutoring is common among primary school students. Attending non-sports tutoring classes for ≥2 h per week increases the risk of screening myopia.

Trifluridine-tipiracil(TAS-102),as a novel fluorouracil-based chemotherapeutic agent,effectively overcomes fluorouracil resistance in colorectal cancer(CRC)through its unique pharmacological mechanisms,providing a critical treatment option for advanced CRC patients.Probiotics have shown unique value in CRC prevention and adjuvant therapy by regulating intestinal flora homeostasis and modulating host immune response.It is worth noting that the combination of chemotherapeutic drugs and probiotics not only enhances the anti-tumor activity through synergistic effects,but also reduces the adverse effects caused by chemotherapeutic drugs.Based on this,this paper systematically reviews the pharmacological properties of TAS-102 and describes its synergistic effects in combination with other antitumor drugs.It also summarizes the synergistic effect of fluorouracil drugs combined with probiotics to enhance the effectiveness and reduce the toxicity,and discusses the potential value of the combination of TAS-102 and probiotics,which provides a new research direction for optimizing the precision treatment of CRC and a scientific basis for improving the quality of life of patients.

Objective To investigate the role and molecular mechanism of SOX4 in Helicobacter pylori(H.pylori)-mediated gastric mucosal epithelial dysplasia.Methods The expression of SOX4 in gastric tissues and cells was analyzed with reverse transcription-polymerase chain reaction(RT-PCR),Western blotting,and immunohistochemical staining.The effects of SOX4 on gastric epithelial cell proliferation and colony formation were determined with CCK-8 and colony formation assays.A PCR array was used to screen downstream target genes involved in H.pylori-induced dysplasia mediated by SOX4.The transcriptional regulation and binding sites of the target gene MLH3 by SOX4 were elucidated with luciferase reporter assay,promoter truncation assay,and chromatin immunoprecipitation(ChIP).Results SOX4 expression was significantly increased in H.pylori-infected gastric tissues(P<0.05).Overexpression of SOX4 markedly enhanced the proliferation and colony formation abilities of normal gastric epithelial cells(P<0.05).Elevated SOX4 led to the dysregulation of MLH3 and other DNA damage repair-related molecules after H.pylori infection in gastric epithelial cells(|logFC|>1,P<0.05).H.pylori promoted MLH3 expression in gastric epithelial cells through SOX4.SOX4 transcriptionally activated MLH3 expression by binding to the 5th site of the MLH3 promoter.The increased expression of SOX4 and MLH3 is associated with poor prognosis of gastric cancer patients.Conclusion SOX4 is closely associated with H.pylori-induced dysplasia in gastric epithelial cells.Upregulation of SOX4 promotes H.pylori-related dysplasia by transcriptionally activating MLH3,leading to the imbalance of proliferation and colony formation in gastric epithelial cells.

Objective To investigate the role and molecular mechanism of SOX4 in Helicobacter pylori(H.pylori)-mediated gastric mucosal epithelial dysplasia.Methods The expression of SOX4 in gastric tissues and cells was analyzed with reverse transcription-polymerase chain reaction(RT-PCR),Western blotting,and immunohistochemical staining.The effects of SOX4 on gastric epithelial cell proliferation and colony formation were determined with CCK-8 and colony formation assays.A PCR array was used to screen downstream target genes involved in H.pylori-induced dysplasia mediated by SOX4.The transcriptional regulation and binding sites of the target gene MLH3 by SOX4 were elucidated with luciferase reporter assay,promoter truncation assay,and chromatin immunoprecipitation(ChIP).Results SOX4 expression was significantly increased in H.pylori-infected gastric tissues(P<0.05).Overexpression of SOX4 markedly enhanced the proliferation and colony formation abilities of normal gastric epithelial cells(P<0.05).Elevated SOX4 led to the dysregulation of MLH3 and other DNA damage repair-related molecules after H.pylori infection in gastric epithelial cells(|logFC|>1,P<0.05).H.pylori promoted MLH3 expression in gastric epithelial cells through SOX4.SOX4 transcriptionally activated MLH3 expression by binding to the 5th site of the MLH3 promoter.The increased expression of SOX4 and MLH3 is associated with poor prognosis of gastric cancer patients.Conclusion SOX4 is closely associated with H.pylori-induced dysplasia in gastric epithelial cells.Upregulation of SOX4 promotes H.pylori-related dysplasia by transcriptionally activating MLH3,leading to the imbalance of proliferation and colony formation in gastric epithelial cells.

Trifluridine-tipiracil(TAS-102),as a novel fluorouracil-based chemotherapeutic agent,effectively overcomes fluorouracil resistance in colorectal cancer(CRC)through its unique pharmacological mechanisms,providing a critical treatment option for advanced CRC patients.Probiotics have shown unique value in CRC prevention and adjuvant therapy by regulating intestinal flora homeostasis and modulating host immune response.It is worth noting that the combination of chemotherapeutic drugs and probiotics not only enhances the anti-tumor activity through synergistic effects,but also reduces the adverse effects caused by chemotherapeutic drugs.Based on this,this paper systematically reviews the pharmacological properties of TAS-102 and describes its synergistic effects in combination with other antitumor drugs.It also summarizes the synergistic effect of fluorouracil drugs combined with probiotics to enhance the effectiveness and reduce the toxicity,and discusses the potential value of the combination of TAS-102 and probiotics,which provides a new research direction for optimizing the precision treatment of CRC and a scientific basis for improving the quality of life of patients.

A 50-year-old male patient diagnosed with extensive stage small cell lung cancer was treated with pamiparib in combination with temozolomide.Five days later,the patient developed fever with fatigue.After 10 days,the patient stopped taking the drug due to worsening symptoms and was diagnosed with chemotherapy-induced myelosuppression(grade 4).The clinicist evaluated the patient's condition and assessed the association of adverse reactions using the Naranjo's evaluation scale,and concluded that myelosuppression may be induced by the combination of pamiparib and temozolomide.After symptomatic treatment,the patient's myelosuppression recovered completely.This article discusses the correlation between myelosuppression and the combination of the two drugs,provides treatment measures for this situation,briefly describes the risk factors of myelosuppression,treatment and prevention,and guides medical personnel to adjust the treatment plan in time according to different individuals in the process of using similar programs,and strengthens the monitoring and education of adverse drug reactions,so as to provide references for safe drug use.

Objective To explore the predictive value of heart rate variability(HRV)for long-term prognosis in elderly patients with stable coronary heart disease(CHD)based on dynamic electro-cardiogram(ECG).Methods A retrospective trial was conducted on 402 elderly patients with sta-ble CHD admitted to our hospital from January 2015 to December 2018,and all of them were fol-lowed up for 5 years.According to occurrence of major adverse cardiovascular events(MACE)or not,they were divided into a MACE group(n=102)and a control group(n=300).The main clin-ical characteristics and differences in HRV were compared between the two groups.Multivariate logistic regression analysis and ROC curve analysis were used.Results Advanced age,larger ratio of diabetes,more severe coronary artery stenosis,and higher low-frequency power and ratio of low-frequency power/high-frequency power,but lower left ventricular ejection fraction(LVEF)and high-frequency power were observed in the MACE group than the control group(P＜0.01).There was also statistical difference in use of hypoglycemic drugs between the two groups during the follow-up period(P＜0.01).Multivariate logistic regression analysis showed that diabetes,age ≥80 years,LVEF＜50％,coronary artery stenosis ≥70％and ratio of low-frequency power/high-frequency power＞1.16 were independent influencing factors for MACE in elderly patients with stable CHD within 5 years(P＜0.05,P＜0.01).ROC curve analysis indicated that the AUC value for low-frequency power and ratio of low-frequency power/high-frequency power in predic-ting MACE occurrence within 5 years was 0.801(95％CI:0.749-0.854,P=0.000)and 0.798(95％CI:0.752-0.844,P=0.000),respectively,and the value of high-frequency power in predic-ting the absence of MACE was 0.629(95％CI:0.566-0.692,P=0.000).Conclusion HRV is an independent influencing factor for MACE occurrence within 5 years in elderly patients with stable CHD,and it shows certain predictive value for MACE occurrence within 5 years in these patients.

Objective In this study,the diversity of the TCR β chain CDR3 in peripheral blood of patients with different typical Traditional Chinese Medicine(TCM)syndromes of liver cirrhosis was analyzed by immune repertoire sequencing,the material basis and regularity of the syndromes of liver cirrhosis was discussed.Methods 20 patients with cirrhosis,including liver and gallbladder damp heat(LGHD),liver depression and spleen deficiency(LDSD),and liver and kidney yin deficiency(LKYD)were enrolled into case group,and 10 healthy patients were used as the healthy control group.DNA was extracted from peripheral blood samples,and multiplex PCR amplification of TCR β chain CDR3 was performed,followed by high-throughput sequencing of the products to analyze the diversity of the TCR β chain CDR3.Results The nt sequence numbers unique to CDR3 and aa sequence numbers unique to CDR3 of LDSD between liver cirrhosis syndromes were less than LKYD(P<0.05).Clonality,Pielous,Shannon.Index and DE50 of LGHD and LKYD had significant differences(P<0.05)between two groups,as well as the frequency of multiple fragments in V and J regions and V-J gene recombination of LGHD vs.LDSD,LGHD vs.LKYD,and LKYD vs.LDSD,respectively(P<0.05).LGHD vs.LDSD,TRBV21-1,TRBV12-4,TRBV11-1 subtype and 7 pairs of V-J recombination have statistical differences(P<0.05).LGHD vs.LKYD,TRBV10-2,TRBV7-6,TRBV5-8 subtypes and 30 pairs of V-J recombination were statistically different(P<0.05).LDSD vs.LKYD,there were statistical differences between TRBJ1-5 subtype and 18 pairs of V-J recombination(P<0.05).Conclusions The present study was conducted to find that the diversity of TCR CDR3 in liver cirrhosis syndrome is significantly different and conforms to the regularity of syndrome from excess to deficiency by explore the immunological characteristics of different TCM syndromes of liver cirrhosis,and to provide new support for the objective basis of"combination of disease and TCM syndrome"and"diagnosis and treatment".We explored the different expression patterns and specificity of adaptive immune gene rearrangement in patients with different TCM syndromes to identify different expression patterns and specific markers of adaptive immune gene rearrangements of typical TCM syndromes in liver cirrhosis.