Circadian rhythms are core regulatory mechanisms that evolved to align biological functions with the Earth's rotation. These rhythms are conserved across organisms from unicellular life to multicellular species and play essential roles in metabolism, immune responses, and sleep-wake cycle. Circadian disruptions are strongly associated with various diseases. Over the past decades, genetic studies in Drosophila and mice have identified key conserved clock genes and uncovered transcription-translation feedback loops governing circadian regulation. Additionally, rhythmic neurons in the brain integrate complex neural circuits to precisely regulate physiological and behavioral rhythms. This review highlights recent advances in understanding the neuronal circuit mechanisms of rhythmic neurons in the Drosophila brain and discusses future directions for translating circadian rhythm research into chronomedicine and precision therapies.
Animals ; Circadian Rhythm/genetics* ; Neurons/physiology* ; Drosophila/physiology* ; Brain/physiology* ; Nerve Net/physiology*

OBJECTIVE: To explore clinical effects of bone setting manipulation combined with pry reduction and Kirschner needle internal fixation in treating SandersⅡ-Ⅲ calcaneal fracture. METHODS: Clinical data of 52 patients with types Sanders Ⅱand Ⅲ calcaneal fracture (foot) treated with bone-setting manipulation combined with pry reduction and Kirscher needle internal fixation from July 2017 to July 2019 were retrospectively analyzed, including 43 males and 9 females, aged from 31 to 72 years old with an average of (50.83±10.48) years old; 15 patients with Sanders typeⅡ and 37 patients with Sanders type Ⅲ. The changes of Bühler angle, Gissane angle, calcaneus width and calcaneus height before operation and 24 months after operation were compared, and Maryland foot function score was performed to evaluate clinical effects. RESULTS: All patients were followed up from 24 to 60 months with an average of (41.50±9.86)months. The fracture healed normally and the healing time was (11.00±0.95) weeks. Bühler angle, Gissane angle, calcaneal bone width and calcaneal bone height were increased from (16.37±8.36)°, (96.27±9.62)°, (46.82±4.67) mm, (38.41±3.58) mm before operation to (31.48±8.24)°, (111.62±8.69)°, (42.06±4.83) mm, (44.21±3.82) mm at 24 months after operation, and the difference were statistically significant (P<0.01). Postoperative Maryland score at 24 months was (93.04±8.83), 40 patients got excellent result, 7 good and 5 fair. CONCLUSION Orthopedic manipulation combined with percutaneous reduction and Kirschner wire internal fixation could significantly improve Bühler angle, Gissane angle, width, and height of Sanders typeⅡ and Ⅲ calcaneal fractures, and the curative effect is satisfactory.
Humans ; Male ; Female ; Calcaneus/surgery* ; Middle Aged ; Fracture Fixation, Internal/methods* ; Adult ; Aged ; Fractures, Bone/therapy* ; Retrospective Studies ; Bone Wires ; Manipulation, Orthopedic/methods*

OBJECTIVE: To evaluate the association between erectile dysfunction (ED) and myocardial infarction (MI) using two sample Mendelian randomization. METHODS: A Mendelian randomization study was conducted using comprehensive data on ED and MI from extensive genome-wide association data. Using inverse variance weighted analysis for causal relationships, and correct for confounding factors using multivariate Mendelian randomization, the potential mediating effects were evaluated as well. Based on Genecard data, the genes related to ED and MI were identified. Molecular docking was used to reveal spontaneously bound drug molecules. RESULTS: Our study found that exposure to ED was a risk factor for MI (OR: 1.001 0, 95% CI: 1.000 2－1.001 8, P=0.017 7), which also held true in the validation dataset (OR: 1.028 5, 95% CI: 1.005 0－1.052 6, P=0.017 2). No statistically significant heterogeneity or horizontal pleiotropy was found. The results of reverse Mendelian randomization analysis showed any reverse causal relationship between ED and MI. In multivariate Mendelian randomization analysis, after excluding confounding factors (excluding triglycerides and high-density lipoprotein), the P-value remained less than 0.05, and the OR ranged from 1.000 1 to 1.000 7, indicating that ED was still a risk factor for MI. In the mediation analysis, it was found that the current mediation ratio of smoking to MI was 13.06%. In summary-data-based mendelian randomization analysis, it was found that the gene PTPN11 was a common target gene for MI and ED (OR=0.990, P<0.001). Subsequent molecular docking with sildenafil, clopidogrel, and dapoxetine could spontaneously bind to the PTPN11 gene receptor. CONCLUSION There is a causal relationship between ED and MI, with smoking as a potential mediating factor, and the gene PTPN11 being a co-target gene.
Humans ; Male ; Mendelian Randomization Analysis ; Myocardial Infarction/genetics* ; Erectile Dysfunction/complications* ; Risk Factors ; Genome-Wide Association Study ; Molecular Docking Simulation ; Polymorphism, Single Nucleotide

Salvia miltiorrhiza (Danshen) is a traditional Chinese herb that is commonly known for its cardiovascular and hepatoprotective benefits. Recent studies have confirmed that Danshen and its bioactive components can influence gut microbial homeostasis, thereby affecting Helicobacter pylori (HP) colonization in the human stomach. HP is a bacterial pathogen associated with various gastrointestinal diseases. Current HP treatments mainly involve antibiotics and proton pump inhibitors. However, their efficacy is strongly compromised by the rapid emergence of antibiotic resistance in HP and genetic heterogeneity among patients. The interaction between Danshen and gut microbial status provides a novel perspective for HP treatment. Understanding the medical properties of Danshen in altering gut microbiota and eliminating HP, as well as the underlying mechanisms, is important for improving human gastrointestinal healthcare. This review investigates the interaction between Danshen and gut microbiota and its impact on HP infection using databases including Web of Science, PubMed, and Google Scholar. We explored the unconventional intersection between Danshen, gut microbiota, and HP infection, shedding light on their intricate interplay and potential therapeutic implications. A comprehensive understanding of this interaction provides valuable insights into developing novel therapeutic strategies that target the gut microbiota to mitigate HP-associated gastrointestinal disorders. Please cite this article as: Li SJ, Miao JX, Wang F, Wang HY, Ma YW, Jiang Y, Xue X. Salvia miltiorrhiza components and gut microbiota interactions in Helicobacter pylori infection. J Integr Med. 2025; 23(5):462-470.
Salvia miltiorrhiza/chemistry* ; Gastrointestinal Microbiome/drug effects* ; Humans ; Helicobacter Infections/microbiology* ; Helicobacter pylori/drug effects* ; Drugs, Chinese Herbal/therapeutic use*

Liver fibrosis is a dynamic wound-healing response characterized by the agglutination of the extracellular matrix (ECM). Si-Wu-Tang (SWT), a traditional Chinese medicine (TCM) formula, is known for treating gynecological diseases and liver fibrosis. Our previous studies demonstrated that long non-coding RNA H19 (H19) was markedly upregulated in fibrotic livers while its deficiency markedly reversed fibrogenesis. However, the mechanisms by which SWT influences H19 remain unclear. Thus, we established a bile duct ligation (BDL)-induced liver fibrosis model to evaluate the hepatoprotective effects of SWT on various cells in the liver. Our results showed that SWT markedly improved ECM deposition and bile duct reactions in the liver. Notably, SWT relieved liver fibrosis by regulating the transcription of genes involved in the cytoskeleton remodeling, primarily in hepatic stellate cells (HSCs), and influencing cytoskeleton-related angiogenesis and hepatocellular injury. This modulation collectively led to reduced ECM deposition. Through extensive bioinformatics analyses, we determined that H19 acted as a miRNA sponge and mainly inhibited miR-200, miR-211, and let7b, thereby regulating the above cellular regulatory pathways. Meanwhile, SWT reversed H19-related miRNAs and signaling pathways, diminishing ECM deposition and liver fibrosis. However, these protective effects of SWT were diminished with the overexpression of H19 in vivo. In conclusion, our study elucidates the underlying mechanisms of SWT from the perspective of H19-related signal networks and proposes a potential SWT-based therapeutic strategy for the treatment of liver fibrosis.
Humans ; RNA, Long Noncoding/genetics* ; Liver Cirrhosis/genetics* ; Liver/metabolism* ; Hepatic Stellate Cells/pathology* ; MicroRNAs/metabolism* ; Extracellular Matrix/metabolism* ; Drugs, Chinese Herbal

Objective To investigate the relationship between gene mutation characteristics and immunological markers in patients with small cell lung cancer.Methods From January 2019 to 2020,155 patients with small cell lung cancer were admitted.Gene mutations were detected in these patients using target gene capture and sequencing method.Moreover,the tumor mutational burden(TMB)and expression of PD-L1 in some patients were detected.Results A total of 326 gene mutations were detected in the patients,the most significant of which were TP53 and RB1.Among the 8 genes with mutation frequency higher than 15％,patients with KMT2D,KMT2C,FAT1 and NOTCH1 mutations had higher TMB than those without mutation,and the difference was statistically significant(P＜0.05).Conclusion The most common mutated genes in patients with small cell lung cancer are TP53 and RB1.KMT2D,KMT2C,FAT1 and NOTCH1 may be potential markers for the efficacy of immunotherapy in small cell lung cancer.

Objective:To evaluate the efficacy of visualized precise lung expansion for determining the intersegmental plane in thoracoscopic segmentectomy.Methods:Sixty-four American Society of Anesthesiologists Physical Status classification Ⅰ or Ⅱ patients, regardless of gender, aged 33-77 yr, with body mass index of 16-34 kg/m 2, undergoing elective thoracoscopic segmentectomy under general anesthesia, were included. They were preoperatively reconstructed with 3D CT bronchovascularization to reconstruct the pulmonary vasculature, bronchus, and the virtual intersegmental planes of the lungs. The patients were divided into 2 groups ( n=32 each) using a random number table method: visualized precise lung expansion group (group V) and modified expansion and atrophy group (group E). Group V used visualized precision lung expansion to determine the intersegmental planes, and group E used the modified expansion and atrophy method to determine the intersegmental planes. The intraoperative intersegmental plane determination time, target segmental bronchus identification and treatment time, anesthesia time, operation time, postoperative air leakage, pulmonary atelectasis, fever, occurrence of lung infection, postoperative 24 h drainage volume, drain removal time and hospitalization time were recorded in the two groups. Results:Compared with group E, the intersegmental plane determination time, target segment bronchial identification and treatment time, anesthesia time and operation time were significantly shortened in group V( P<0.05).There were no significant differences between groups in the 24 h postoperative drainage volume, drain removal time, hospitalization time or incidence of postoperative pulmonary complications ( P>0.05). Conclusions:Compared with the modified expansion and atrophy method, visualized precise lung expansion can effectively shorten the intersegmental plane determination time in thoracoscopic segmentectomy.

Objective:To investigate the predictive value of pregnancy-associated plasma protein A(PAPP-A),fasting blood glucose(FPG),body mass index(BMI)and age in gestational diabetes mellitus(GDM)during the first trimester.Methods:A retrospective analysis was performed on 792 pregnant women who underwent pre-natal examination and delivered in Sichuan Provincial Maternal and Child Health Care Hospital from December 2021 to June 2022.They were divided into GDM group(232 cases)and control group(560 cases)according to whether they had GDM.The clinical data,serum PAPP-A median multiple(PAPP-A MoM)in early pregnancy and FPG levels were compared between the two groups.The indicators with statistical significance in univariate analy-sis were included in multivariate Logistic regression analysis to analyze the related factors affecting the occurrence of GDM.The receiver operating curve(ROC)and area under the curve(AUC)of different indexes were plotted to compare the efficacy of GDM prediction.Results:①The age,pre pregnancy BMI,early pregnancy FPG and the proportion of assisted reproductive technology in GDM group were higher than those in control group,and the differences were statistically significant(P＜0.05).The early pregnancy PAPP-A MoM level in GDM group was lower than that in control group,and the difference was statistically significant(P＜0.05).②Multivariate Logistic regression analysis showed that older age,lager pre-pregnancy BMI and lager FPG in the first trimester were in-dependent risk factors for GDM occurrence(OR＞1,P＜0.05),while an increase of PAPP-A MoM in the first tri-mester was a protective factor(OR＜1,P＜0.05).③ROC showed that the combination of PAPP-A MoM in early pregnancy,FPG in early pregnancy,BMI in pre-pregnancy and age had the highest AUC(0.752)when predicting GDM,with a sensitivity of 55.6％and a specificity of 84.3％.Conclusions:The combined screening of serologi-cal(PAPP-A +FPG)and clinical data(pre-pregnancy BMI +age)in early pregnancy has a high clinical application prospect and can be popularized.

Tumor-associated macrophages(TAMs)are the predominant cell group in the tumor microenvironment(TME)and are the most important regulatory cells of immune system suppression and tumor cell proliferation in TIME.Src homology-2 domain-containing protein tyrosine phosphatase 2(SHP-2)is a non-receptor protein tyrosine phosphatase that plays an important role in the transmission of signals from the cell surface to the nucleus.SHP-2 is a key intracellular regulatory factor mediating cell proliferation and differentiation and is involved in a variety of growth factor and cytokine signaling pathways linking the cell surface to the nucleus.Recent studies have shown that SHP-2 is a key enzyme in determining the function of TAMs,but because of its variable function,it plays different or even opposite roles in different solid TMEs.This paper reviews the function of SHP-2 in TAMs and related solid tumors to provide a comprehensive reference for tumor immunity and targeted therapy research.

ObjectiveTo understand the process and influencing factors affecting the utilization of influenza vaccination services and vaccination decision-making among the elderly in Shanghai, to explore the delivery of influenza vaccination services and the difficulties faced by the health service system, and to provide guidance for optimizing immunization strategies. MethodsBased on the vaccine hesitancy determinants matrix, semi-structured personal interviews were conducted with stakeholders involved in influenza vaccination services in Shanghai from January to February 2024, using a purposive sampling method. Participants were included until thematic saturation was achieved. Interview data were audio-recorded, transcribed, coded, and organized using NVivo 20 software, and analyzed using the thematic framework method. ResultsA total of 25 interviewees were included, including 9 medical staff, 12 elderly people aged 60 and above, and 4 family members. The study found that Shanghai had a well-managed and standardized influenza vaccination service. However, the promotion of vaccine-related information at the grassroots level was passive and limited. Out-of-pocket payment of the vaccine and cultural beliefs of the elderly negatively impacted vaccination rates. Meanwhile, recommendations from family, friends, and medical staff facilitated vaccination, although the impact varied depending on the type of medical staff. Neighborhood committees in townships and streets played a crucial role in delivering vaccination information to the target population. Additionally, the internet, social media, and the COVID-19 vaccine had both positive and negative impacts on influenza vaccination. Strategic optimization of vaccination should prioritize price concessions, enhance publicity strategies, and improve awareness, professionalism, and willingness among medical and healthcare workers to recommend vaccination. ConclusionThe influenza vaccination service in Shanghai is well-managed and standardized. However, it is essential to consider the influence of family and other support systems on the elderly. It is also necessary to enhance the professionalism, service awareness, and willingness to recommend among the medical staff. Furthermore, systematic interventions and publicity efforts should be effectively integrated with social media and the functions of neighborhood committees.