Objective: To explore the balance of peripheral blood T helper 17 cells/regulatory T cell (Th17/Treg) ratio and the polarization ratio of M1 and M2 macrophages in lower extremity arteriosclerosis obliterans (ASO). Methods: A rat model of lower extremity ASO was established, and blood samples from patients with lower extremity ASO before and after surgery were obtained. ELISA was used to detect interleukin 6 (IL-6), IL-10, and IL-17. Real-time RCR and Western blot analyses were used to detect Foxp3, IL-6, IL-10, and IL-17 expression. Moreover, flow cytometry was applied to detect the Th17/Treg ratio and M1/M2 ratio. Results: Compared with the control group, the iliac artery wall of ASO rats showed significant hyperplasia, and the concentrations of cholesterol and triglyceride were significantly increased (P<0.01), indicating the successful establishment of ASO. Moreover, the levels of IL-6 and IL-17 in ASO rats were pronouncedly increased (P<0.05), while the IL-10 level was significantly decreased (P<0.05). In addition to increased IL-6 and IL-17 levels, the mRNA and protein levels of Foxp3 and IL-10 in ASO rats were significantly decreased compared with the control group. The Th17/Treg and M1/M2 ratios in the ASO group were markedly increased (P<0.05). These alternations were also observed in ASO patients. After endovascular surgery (such as percutaneous transluminal angioplasty and arterial stenting), all these changes were significantly improved (P<0.05). Conclusions: The Th17/Treg and M1/M2 ratios were significantly increased in ASO, and surgery can effectively improve the balance of Th17/Treg, and reduce the ratio of M1/M2, and the expression of inflammatory factors.

The incidence of intrahepatic cholangiocarcinoma (ICC) continues to rise, and there are no effective drugs to treat it. The immune microenvironment plays an important role in the development of ICC and is currently a research hotspot. Icaritin (ICA) is an innovative traditional Chinese medicine for the treatment of advanced hepatocellular carcinoma. It is considered to have potential immunoregulatory and anti-tumor effects, which is potentially consistent with the understanding of "Fuzheng" in the treatment of tumor in traditional Chinese medicine. However, whether ICA can be used to treat ICC has not been reported. Therefore, in this study, sgp19/kRas, an in situ ICC mouse model with intact immune system, was selected to evaluate the efficacy of ICA in the treatment of ICC in vivo for the first time, and the effects of ICA on the tumor immune microenvironment of ICC mice were analyzed by flow cytometry. This experiment was approved by the Experimental Animal Ethics Committee of Capital Medical University (approval number: AEEI-2023-138). In this study, sgp19/kRas ICC mouse model was treated with oral gavage of 100 mg·kg^-1 ICA. We found that ICA significantly inhibited tumor growth and tumor cell proliferation in the sgp19/kRas ICC mouse model after 3 weeks of treatment. Flow cytometry analysis indicated that ICA treatment markedly reduced the proportion of M2 macrophages and increased the number of CD3⁺CD4⁺ T cells. In vitro experiments demonstrated that ICA promoted macrophage polarization towards the M1 phenotype while inhibiting polarization towards the M2 phenotype. Furthermore, transcriptomic analysis suggested that ICA enhanced Toll-like receptor 9 (TLR9) expression, influencing macrophage nitric oxide metabolism synthesis pathways and receptor-related activities, thereby regulating macrophage polarization. In summary, this study demonstrates that ICA treatment significantly delays tumor progression in sgp19/kRas ICC mouse models. Mechanistically, ICA may achieve its anti-ICC effects by upregulating TLR9 receptor expression levels, promoting macrophage polarization towards the M1 phenotype, and altering the tumor immune microenvironment.

Extracellular vesicles(EVs)are nano-sized membranous vesicles secreted and released by cells into the extracellular matrix.They carry bioactive molecules derived from parent cells and are regarded as media for intercellular communication and material transfer.Compared to synthetic nanocarriers,EVs possess lower immunogenicity,better biocompatibility,and enhanced ability to traverse biological barriers,making them ideal carriers for nucleic acid drug delivery.This article reviewed the loading technologies of EVs as carriers for nucleic acid drugs,with an in-depth analysis and discussion of the performance and application progress of endogenous and exogenous loading methods,strategies for evaluating nucleic acid loading quality,and the application of EV-mediated nucleic acid delivery in cancer therapy.Finally,the advantages and existing challenges of EVs as nucleic acid delivery vehicles in cancer treatment were summarized and their future development prospects in clinical applications was anticipated.

Objective To observe the efficacy and safety of Morinda officinalis oligosaccharides in the continuation treatment of mild and moderate depression.Methods An open,single-arm,multi-center design was adopted in our study.Adult patients with mild and moderate depression who had received acute treatment of Morinda officinalis oligosaccharides were enrolled and continue to receive Morinda officinalis oligosaccharides capsules for 24 weeks,the dose remained unchanged during continuation treatment.The remission rate,recurrence rate,recurrence time,and the change from baseline to endpoint of Hamilton Depression Scale(HAMD),Hamilton Anxiety Scale(HAMA),Clinical Global Impression-Severity(CGI-S)and Arizona Sexual Experience Scale(ASEX)were evaluated.The incidence of treatment-related adverse events was reported.Results The scores of HAMD-17 at baseline and after treatment were 6.60±1.87 and 5.85±4.18,scores of HAMA were 6.36±3.02 and 4.93±3.09,scores of CGI-S were 1.49±0.56 and 1.29±0.81,scores of ASEX were 15.92±4.72 and 15.57±5.26,with significant difference(P＜0.05).After continuation treatment,the remission rate was 54.59％(202 cases/370 cases),and the recurrence rate was 6.49％(24 cases/370 cases),the recurrence time was(64.67±42.47)days.The incidence of treatment-related adverse events was 15.35％(64 cases/417 cases).Conclusion Morinda officinalis oligosaccharides capsules can be effectively used for the continuation treatment of mild and moderate depression,and are well tolerated and safe.

OBJECTIVE: To derive the Chinese medicine (CM) syndrome classification and subgroup syndrome characteristics of ischemic stroke patients. METHODS: By extracting the CM clinical electronic medical records (EMRs) of 7,170 hospitalized patients with ischemic stroke from 2016 to 2018 at Weifang Hospital of Traditional Chinese Medicine, Shandong Province, China, a patient similarity network (PSN) was constructed based on the symptomatic phenotype of the patients. Thereafter the efficient community detection method BGLL was used to identify subgroups of patients. Finally, subgroups with a large number of cases were selected to analyze the specific manifestations of clinical symptoms and CM syndromes in each subgroup. RESULTS: Seven main subgroups of patients with specific symptom characteristics were identified, including M3, M2, M1, M5, M0, M29 and M4. M3 and M0 subgroups had prominent posterior circulatory symptoms, while M3 was associated with autonomic disorders, and M4 manifested as anxiety; M2 and M4 had motor and motor coordination disorders; M1 had sensory disorders; M5 had more obvious lung infections; M29 had a disorder of consciousness. The specificity of CM syndromes of each subgroup was as follows. M3, M2, M1, M0, M29 and M4 all had the same syndrome as wind phlegm pattern; M3 and M0 both showed hyperactivity of Gan (Liver) yang pattern; M2 and M29 had similar syndromes, which corresponded to intertwined phlegm and blood stasis pattern and phlegm-stasis obstructing meridians pattern, respectively. The manifestations of CM syndromes often appeared in a combination of 2 or more syndrome elements. The most common combination of these 7 subgroups was wind-phlegm. The 7 subgroups of CM syndrome elements were specifically manifested as pathogenic wind, pathogenic phlegm, and deficiency pathogens. CONCLUSIONS There were 7 main symptom similarity-based subgroups in ischemic stroke patients, and their specific characteristics were obvious. The main syndromes were wind phlegm pattern and hyperactivity of Gan yang pattern.
Humans ; Syndrome ; Ischemic Stroke ; Medicine, Chinese Traditional ; Liver ; Phenotype

Objectives: To investigate the factors influencing the height of anterior peritoneal reflection (APR) for patients with rectal cancer, and to analyze the relationship between the APR and the lateral lymph node metastasis. Methods: Clinical data of 432 patients with tumor located within and below APR were retrospectively collected from the rectal cancer database at the Department of General Surgery, Peking Union Medical College Hospital from August 2020 to September 2022. Ninty-eight non-rectal cancer patients were also enrolled as a control group. There were 308 males and 124 females in the tumor group, aged (M(IQR)) 62 (16) years (range: 24 to 85 years) and 53 males and 45 females in the control group, aged 60 (22) years (range: 27 to 87 years). The APR height, pelvis, and tumor-related parameters were measured by MRI. A multifactor linear regression model was established to analyze the dependent correlation factors of APR height. These factors of the two groups were matched by propensity score matching and their APR heights were compared after matching. An ordinal Logistic regression model was established to explore the relationship between APR-related parameters and radiographic lateral lymph node metastasis. Results: The APR height of the tumor group was (98.7±14.4) mm (range: 43.3 to 154.0 mm) and the control group was (95.1±12.7) mm (range: 68.0 to 137.9 mm). Multivariable linear regression revealed that the greater the weight (B=0.519, 95%CI: 0.399 to 0.640, P<0.01), the anterior pelvic depth (B=0.109, 95%CI: 0.005 to 0.213, P=0.039) and the smaller the bi-ischial diameter (B=-0.172, 95%CI:-0.294 to -0.049, P=0.006), the higher the APR height. The tumor group had a higher APR height than the control group after propensity score matching ((98.3±14.2) mm vs. (95.1±12.7) mm, t=-1.992, P=0.047). Ordinal Logistic regression indicated that the longer segment of the tumor invade the nonperitoneal rectum was an independent influencing factor of radiographic lateral lymph node metastasis (OR=1.016, 95%CI: 1.002 to 1.030, P=0.021), while the distance between the anal verge and the tumor was not (OR=0.986, 95%CI: 0.972 to 1.000, P=0.058). Conclusions: The higher the weight, the deeper and narrower the pelvis, the higher the APR height. There is a certain relationship between APR and lateral lymph node metastasis on imaging.

Objective: To evaluate the efficacy of endoscopic transnasal surgery for sinonasal and skull base adenoid cystic carcinoma (ACC), and to analyze the prognostic factors. Methods: Data of 82 patients (43 females and 39 males, at a median age of 49 years old) with sinonasal and skull base ACC who were admitted to XuanWu Hospital, Capital Medical University between June 2007 and June 2021 were analyzed retrospectively. The patients were staged according to American Joint Committee on Cancer (AJCC) 8th edition. The disease overall survival(OS) and disease-free survival(DFS) rates were calculated by Kaplan-Meier analysis. Cox regression model was used for multivariate prognostic analysis. Results: There were 4 patients with stage Ⅱ, 14 patients with stage Ⅲ, and 64 patients with stage Ⅳ. The treatment strategies included purely endoscopic surgery (n=42), endoscopic surgery plus radiotherapy (n=32) and endoscopic surgery plus radiochemotherapy (n=8). Followed up for 8 to 177 months, the 5-year OS and DFS rates was 63.0% and 51.6%, respectively. The 10-year OS and DFS rates was 51.2% and 31.8%, respectively. The multivariate Cox regression analysis showed that late T stage and internal carotid artery (ICA) involvement were the independent prognostic factors for survival in sinonasal and skull base ACC (all P<0.05). The OS of patients who received surgery or surgery plus radiotherapy was significantly higher than that of patients who received surgery plus radiochemotherapy (all P<0.05). Conclusions: Endoscopic transonasal surgery or combing with radiotherapy is an effective procedure for the treatment of sinonasal and skull base ACC. Late T stage and ICA involvement indicate poor prognosis.
Male ; Female ; Humans ; Middle Aged ; Carcinoma, Adenoid Cystic/surgery* ; Retrospective Studies ; Skull Base/pathology* ; Disease-Free Survival ; Prognosis

Objective:To investigate the efficacy of metagenomic next generation sequencing (mNGS) in the etiological diagnosis of patients with spinal infection, so as to provide reference for timely diagnosis and treatment.Methods:A total of 40 patients with suspected spinal infection admitted to the Department of Infectious Diseases in Henan Provincial People′s Hospital from January 2020 to July 2022 were included. The results of tissue culture, histopathological examination and tissue mNGS detection were analyzed retrospectively. According to the clinical diagnose, the patients were divided into the spinal infection group (28 cases) and the non-spinal infection group (12 cases). The positive rate, sensitivity and specificity of mNGS and tissue culture in the pathogen detection of patients with spinal infection were compared. McNemar test was used for statistical analysis.Results:There were 23 males and 17 females in 40 patients. The positive rate of mNGS was higher than that of tissue culture (75.0%(30/40) vs 12.5%(5/40)), and the difference was statistically significant ( χ2=0.08, P<0.001). Based on clinical diagnostic criteria, the sensitivity of mNGS in the diagnosis of spinal infection was higher than that of tissue culture (82.1% vs 17.9%), with a statistically significant difference ( χ2=0.02, P<0.001), while the specificity compared to the tissue culture (33.3% vs 100.0%), the difference was not statistically significant ( P>0.05). Conclusions:mNGS has a high pathogen detection rate and sensitivity in the etiological diagnosis of patients with spinal infection, which could provide clinical guidance for the diagnosis and treatment of patients with spinal infection.

The target gene sequences of the novel coronaviruses obtained by sequencing were compared with the reference sequences to analyze the genetic variation of the two cases of the novel coronaviruses from Inner Mongolia Autonomous Region in 2022 and to explore the sources of infection. The results showed that the two sequences belonged to different evolutionary branches, Delta (AY.122) and Omicron (BA.1.1), respectively. hCoV-19/Inner Mongolia/IVDC-591/2022 had 48 single nucleotide polymorphisms on the genome sequences, sharing 40 nucleotide mutation sites with a Mongolian strain; hCoV-19/Inner Mongolia/IVDC-592/2022 genome shared 57 nucleotide mutation sites with a UK strain, and the nucleotide mutation site identity was 100% (57/57). Phylogenetic analysis showed that the target gene sequences were not directly related to domestic novel coronavirus sequences during the same period, but were related to isolates from Europe and Mongolia.
Humans ; COVID-19 ; SARS-CoV-2/genetics* ; Phylogeny ; Genome, Viral ; Nucleotides ; Sequence Analysis

The target gene sequences of the novel coronaviruses obtained by sequencing were compared with the reference sequences to analyze the genetic variation of the two cases of the novel coronaviruses from Inner Mongolia Autonomous Region in 2022 and to explore the sources of infection. The results showed that the two sequences belonged to different evolutionary branches, Delta (AY.122) and Omicron (BA.1.1), respectively. hCoV-19/Inner Mongolia/IVDC-591/2022 had 48 single nucleotide polymorphisms on the genome sequences, sharing 40 nucleotide mutation sites with a Mongolian strain; hCoV-19/Inner Mongolia/IVDC-592/2022 genome shared 57 nucleotide mutation sites with a UK strain, and the nucleotide mutation site identity was 100% (57/57). Phylogenetic analysis showed that the target gene sequences were not directly related to domestic novel coronavirus sequences during the same period, but were related to isolates from Europe and Mongolia.
Humans ; COVID-19 ; SARS-CoV-2/genetics* ; Phylogeny ; Genome, Viral ; Nucleotides ; Sequence Analysis