Biomolecular condensates are formed through phase separation of biomacromolecules such as proteins and RNAs. These condensates exhibit liquid-like properties that can futher transition into more stable material states. They form complex internal structures via multivalent weak interactions, enabling precise spatiotemporal regulations. However, the use of inconsistent and non-standardized terminology has become increasingly problematic, hindering academic exchange and the dissemination of scientific knowledge. Therefore, it is necessary to discuss the terminology related to biomolecular condensates in order to clarify concepts, promote interdisciplinary cooperation, enhance research efficiency, and support the healthy development of this field.

BACKGROUND: Biomarkers-based prediction of long-term risk of acute coronary syndrome (ACS) is scarce. We aim to develop a risk score integrating clinical routine information (C) and plasma biomarkers (B) for predicting long-term risk of ACS patients. METHODS: We included 2729 ACS patients from the OCEA (Observation of cardiovascular events in ACS patients). The earlier admitted 1910 patients were enrolled as development cohort; and the subsequently admitted 819 subjects were treated as validation cohort. We investigated 10-year risk of cardiovascular (CV) death, myocardial infarction (MI) and all cause death in these patients. Potential variables contributing to risk of clinical events were assessed using Cox regression models and a score was derived using main part of these variables. RESULTS: During 16,110 person-years of follow-up, there were 238 CV death/MI in the development cohort. The 7 most important predictors including in the final model were NT-proBNP, D-dimer, GDF-15, peripheral artery disease (PAD), Fibrinogen, ST-segment elevated MI (STEMI), left ventricular ejection fraction (LVEF), termed as CB-ACS score. C-index of the score for predication of cardiovascular events was 0.79 (95% CI: 0.76-0.82) in development cohort and 0.77 (95% CI: 0.76-0.78) in the validation cohort (5832 person-years of follow-up), which outperformed GRACE 2.0 and ABC-ACS risk score. The CB-ACS score was also well calibrated in development and validation cohort (Greenwood-Nam-D'Agostino: P = 0.70 and P = 0.07, respectively). CONCLUSIONS CB-ACS risk score provides a useful tool for long-term prediction of CV events in patients with ACS. This model outperforms GRACE 2.0 and ABC-ACS ischemic risk score.

Drug-induced liver injury(DILI)is a common adverse drug reaction in clinical practice,which can lead to acute liver failure and even death in severe cases.In recent years,with the continuous introduction of new drugs and the expansion of their usage,the incidence and mortality rates of DILI have shown an upward trend,posing significant challenges to public health and clinical treatment.Macrophages,as a crucial component of the innate immune system,exhibit high plasticity and heterogeneity.They can polarize into pro-inflammatory M1 type or anti-inflammatory M2 type in response to microenvironmental signals.Research has demonstrated that macrophage polarization plays a central regulatory role in the occurrence and progression of DILI by influencing various processes such as inflammatory responses,cell apoptosis,and tissue repair.This review focuses on elucidating the regulatory mechanisms and roles of macrophage polarization in DILI,providing a theoretical framework for developing precise immunotherapeutic strategies.

OBJECTIVE: To investigate the effects of Danmu Extract Syrup (DMS) on lipopolysaccharide (LPS)-induced acute lung injury (ALI) in mice and explore the mechanism. METHODS: Seventy-two male Balb/C mice were randomly divided into 6 groups according to a random number table (n=12), including control (normal saline), LPS (5 mg/kg), LPS+DMS 2.5 mL/kg, LPS+DMS 5 mL/kg, LPS+DMS 10 mL/kg, and LPS+Dexamethasone (DXM, 5 mg/kg) groups. After pretreatment with DMS and DXM, the ALI mice model was induced by LPS, and the bronchoalveolar lavage fluid (BALF) were collected to determine protein concentration, cell counts and inflammatory cytokines. The lung tissues of mice were stained with hematoxylin-eosin, and the wet/dry weight ratio (W/D) of lung tissue was calculated. The levels of tumor necrosis factor-α (TNF-α), interleukin (IL)-6 and IL-1 β in BALF of mice were detected by enzyme linked immunosorbent assay. The expression levels of Claudin-5, vascular endothelial (VE)-cadherin, vascular endothelial growth factor (VEGF), phospho-protein kinase B (p-Akt) and Akt were detected by Western blot analysis. RESULTS: DMS pre-treatment significantly ameliorated lung histopathological changes. Compared with the LPS group, the W/D ratio and protein contents in BALF were obviously reduced after DMS pretreatment (P<0.05 or P<0.01). The number of cells in BALF and myeloperoxidase (MPO) activity decreased significantly after DMS pretreatment (P<0.05 or P<0.01). DMS pre-treatment decreased the levels of TNF-α, IL-6 and IL-1 β (P<0.01). Meanwhile, DMS activated the phosphoinositide 3-kinase/protein kinase B (PI3K/Akt) pathway and reversed the expressions of Claudin-5, VE-cadherin and VEGF (P<0.01). CONCLUSIONS DMS attenuated LPS-induced ALI in mice through repairing endothelial barrier. It might be a potential therapeutic drug for LPS-induced lung injury.
Mice ; Male ; Animals ; Proto-Oncogene Proteins c-akt/metabolism* ; Lipopolysaccharides ; Phosphatidylinositol 3-Kinases/metabolism* ; Interleukin-1beta/metabolism* ; Vascular Endothelial Growth Factor A/metabolism* ; Tumor Necrosis Factor-alpha/metabolism* ; Claudin-5/metabolism* ; Acute Lung Injury/chemically induced* ; Lung/pathology* ; Interleukin-6/metabolism* ; Drugs, Chinese Herbal

Objective To explore the acupoint selection rules of acupuncture for the treatment of lower limb spasm after stroke based on data mining technology.Methods Through the computer retrieval of CNKI,Wanfang,VIP,PubMed,EMbase,web of science databases and other databases,the literature that meets the inclusion criteria was selected to establish a database.Descriptive analysis,cluster analysis and association rule analysis were performed on the data through Microsoft Excel 2016,IBM SPSS Statistics 21 and IBM SPSS Modeler 18.0 software.Results(1)A total of 68 acupuncture prescriptions were included,involving 100 acupoints and a total frequency of 536 uses;(2)the top five in terms of frequency of use of acupoints were Yanglingquan(GB34),Zusanli(ST36),Xuanzhong(GB39),Qiuxu(GB40),Sanyinjiao(SP6);(3)the core acupoint pairing was Yanglingquan(GB34)-Xuanzhong(GB39),and five valid clustering clusters were obtained,which were Shenmai(BL62)-Zhaohai(KI6),Weizhong(BL40)-Kunlun(BL60),Xuehai(SP10)-Huantiao(GB30)-Fenglong(ST40)-Zusanli(ST36),Taixi(KI3)-Yinlingquan(SP9)-Sanyinjiao(SP6),Jiexi(ST41)-Taichong(LR3)-Xuanzhong(GB39)-Qiuxu(GB40)-Yanglingquan(GB34).Conclusion Through data mining,it is found that acupuncture treatment of lower limb spasm after stroke is mostly based on Yanglingquan,Zusanli,Xuanzhong,Qiuxu and Xuanzhong.Priority should be given to the application of three yang channels of the foot and five shu acupoint,syndrome differentiation and treatment,and modification should be adjusted according to the syndromes,so as to provide reference for clinical treatment of lower limb spasm after stroke.

Objective To compare the clinical efficacy and pregnancy outcomes of CO2 laser and loop electrosurgical excision procedure(LEEP)surgery in the treatment of cervical high-grade squamous intraepithelial lesion(HSIL)in women of childbearing age.Methods Patients with cervical HSIL of appropriate reproductive age(20-34 years old)who underwent satisfied colposcope,subsequently treated with laser or LEEP between Jan 2019 and Dec 2021 in Obstetrics and Gynecology Hospital,Fudan University were collected.All the patients were interpreted as transformation zone(TZ)type 1/2,and colposcopy biopsy diagnosed as cervical high-grade squamous intraepithelial lesion(HSIL)and received laser or LEEP according to the physician's advice and the patient's wishes.The effectiveness of the two surgeries was evaluated,and postoperative cytology,HPV result,and colposcopic pathology were compared.We monitored the surgical pregnancy rate,pregnancy complications,and pregnancy results after the surgery.Results A total of 566 cases,including 233 laser cases and 333 LEEP cases,were enrolled.There was no significant difference between the two groups in terms of preoperative cytology,HPV distribution,or the length of cervical canal.After 6 months of surgery,91.5%of patients who underwent laser therapy and 86.9%of those who underwent LEEP had normal cytology.The histology cure rate was 91.5%and the HPV conversion rate was 74.6%in both groups.The results of cytology,HPV,and colposcopic pathology had no significant difference between the two groups.The length of postoperative cervical canal was significantly longer in laser group than that in LEEP group[(29.09±3.15)mm vs.(27.05±3.84)mm,P<0.001].There was no statistically significant difference in postoperative pregnancy rate and pregnancy outcome between the two groups.Conclusion Laser ablation and LEEP produce comparable effects pregnancy outcomes in cervical HSIL patients with TZ types 1 and 2,while LEEP has pathologic feedback,so its misdiagnosis of invasive cancer reduce.

Objective To explore the clinical value of vaginoscopy in the diagnosis and treatment of uterine cavity diseases in virgins.Methods We retrospectively reviewed the data of 450 patients who underwent vaginoscopy and traditional hysteroscopy in Obstetrics and Gynecology Hospital,Fudan University from Jan 2020 to Dec 2023,including vaginoscopy group(n=232)and traditional hysteroscopy group(n=218).The average ages of the two groups were 24.9±4.7 years and 25.5±5.4 years,and there was no significant difference between the two groups(P>0.05).The operation time,estimated blood loss,fluid deficit,false passage,surgical failure,incidence of complications and postoperative pain score were compared between vaginoscopy group and traditional hysteroscopy group.Results Compared with the traditional hysteroscopy group,the average operation time in the vaginoscopy group was shorter,the fluid deficit was less,and the VAS pain score was lower,but the rate of surgical failure was higher(7.8%vs.0),all the differences were statistically significant(P<0.05).In terms of complications,the incidence of false passage in the vaginoscopy group was less(0 vs.3.2%)and the rate of hymen injury was lower(0 vs.85.3%),the differences were statistically significant(P<0.05).There was no significant difference in the estimated blood loss between the two groups,and the incidence of postoperative infection was similar in both groups.There were no complications such as uterine perforation and air embolism in both groups.Conclusion Vaginoscopy is safe and effective,more minimally invasive than traditional hysteroscopy,does not damage the hymen,and is suitable for virgins.This technology is worthy of clinical application.

Objective:To preliminarily investigate the clinical outcomes of secondary loop electrosurgical excision procedure (LEEP) combined with transcervical resection of endocervical tissue (i.e., second combined surgeries) in patients with positive endocervical margins following the initial LEEP for high-grade squamous intraepithelial lesion (HSIL) or adenocarcinoma in situ (AIS) of the cervix.Methods:Patients who underwent second combined surgeries due to positive endocervical margins after the initial LEEP for cervical HSIL or AIS at Obstetrics and Gynecology Hospital, Fudan University between August 2015 and September 2023 were included. Postoperative cytological examinations, high-risk human papillomavirus (HR-HPV) testing, colposcopic biopsy results, and cervical canal length were followed up to evaluate the clinical efficacy of second combined surgeries.Results:(1) General clinical data: a total of 67 patients were enrolled, including 34 with cervical HSIL (HSIL group) and 33 with AIS (AIS group). In the HSIL group before the time of initial LEEP, the mean age was (41.3±5.3) years, with all patients positive for HR-HPV preoperatively. Preoperative cytology results revealed ≤low-grade squamous intraepithelial lesion (LSIL) in 13 cases and ≥HSIL in 21 cases. The preoperative cervical canal length was (3.71±0.17) cm. Patients in the AIS group before their the first LEEP were at an average age of (39.1±8.7) years old, with preoperative HR-HPV positive. Among them, 16 cases showed preoperative cytological results of ≤LSIL, while 17 cases showed ≥HSIL. The preoperative cervical canal length was (3.64±0.21) cm. (2) Pathological findings and postoperative follow-up of the HSIL group following second combined surgeries:in the HSIL group, the residual rate of HSIL in the endocervical canal tissue (ECT) was 24% (8/34). Out of the 34 HSIL patients, 10 cases (29%, 10/34) remained with positive endocervical margins post-second combined surgeries. Among these 10 patients, 5 cases (5/10) had no lesion detected in ECT, while the remaining 5 cases (5/10) exhibited HSIL in their ECT. Conversely, 24 patients (71%, 24/34) had negative endocervical margins after second combined surgeries. Of these 24 patients, 3 cases (12%, 3/24) were found to have HSIL in ECT, and 21 cases (88%, 21/24) had no lesion in ECT. During follow-ups conducted at 6 and 12 months post-second combined surgeries, the clearance rates of HR-HPV were 91% (31/34) and 100% (34/34), respectively. Notably, among the 29 patients (85%, 29/34) who were followed up for a period of 2 years or longer, all cases maintained a consistently negative HR-HPV status, highlighting the effectiveness of second combined surgeries in achieving long-term HR-HPV clearance (100%, 29/29). (3) Pathological findings and postoperative follow-up of the AIS group following second combined surgeries: the residual rate of AIS in the ECT following second combined surgeries among AIS patients was 15% (5/33). Out of the 33 AIS patients, 11 cases (33%, 11/33) had positive endocervical margins post-operation, among whom AIS was detected in the ECT of 2 cases (2/11), while 1 case (1/11) was diagnosed with adenocarcinoma in the cervical canal tissue (subsequently underwent radical surgery and was excluded from this study). In contrast, 22 patients (67%, 22/33) had negative endocervical margins post-operation, with AIS found in the ECT of 2 cases (9%, 2/22) and no lesions detected in the remaining 20 cases (91%, 20/22). Follow-up evaluations conducted at 6 and 12 months postoperatively revealed HR-HPV clearance rates of 91% (29/32) and 97% (31/32), respectively. All 32 (100%, 32/32) AIS patients were followed up for a duration of ≥2 years post-second combined surgeries, during which HR-HPV remained consistently negative. (4) Complications and cervical length following second combined surgeries: neither the HSIL group nor the AIS group experienced significant complications such as hemorrhage, infection or cervical canal adhesion. At the 6-month follow-up, the cervical length of both HSIL and AIS patients exceeded 3 cm. By the 12-month follow-up, the cervical length had recovered to 96.5% and 97.5% when compared to the original length, respectively, for the HSIL and AIS groups.Conclusions:For patients with HSIL or AIS who exhibit positive endocervical margins following the initial LEEP procedure, undergoing second combined surgeries presents as an optimal choice. This surgical intervention guarantees thorough excision of the lesion, and subsequent colposcopic follow-up evaluations consistently demonstrate an absence of residual disease or recurrence. Moreover, it augments the rate of sustained HR-HPV negativity, thereby contributing to more favorable clinical outcomes.

Objective:To explore the value of CO 2 laser therapy, photodynamic therapy, and follow-up observation in the management of cervical low-grade squamous intraepithelial lesion (LSIL). Methods:Women diagnosed with cervical LSIL and high risk human papillomavirus (HR-HPV) infection through colposcopy-guided biopsy from January 1, 2021 to December 31, 2023 were collected. According to a 1∶1 ratio, 107 cases were included in each of the laser treatment, photodynamic therapy, and follow-up groups. The complete remission rate and HR-HPV clearance rate were compared during the 6-12 months follow-up period.Results:(1) Comparison of clinical data among the three groups before treatment: the median age of the 321 patients was (34.9±8.1) years. Before treatment, cytological abnormalities were present in 51.7% (166/321) of patients, and 35.2% (113/321) had human papillomavirus (HPV) 16/18 infections. The accuracy rate of colposcopic diagnosis was 69.2% (222/321). Age, cytology results, HPV 16/18 infection, and colposcopy diagnosis in the laser group, photodynamic group, and follow-up group were compared, and there were not statistically significant differences (all P>0.05). (2) During the 6-12 months follow-up period, the complete remission rate was 89.7% (96/107) in the laser group, slightly higher than the 86.9% (93/107) in the photodynamic group, with no statistical difference between the two groups ( χ2=0.41, P=0.523). However, both were significantly higher than the 64.5% (69/107) in the follow-up group ( χ2=19.30, P<0.001; χ2=14.63, P<0.001). The HR-HPV clearance rates in the laser and photodynamic groups were 73.8% (79/107) and 68.2% (73/107), respectively, both significantly higher than the 32.7% (35/107) in the follow-up group ( χ2=36.34, P<0.001; χ2=26.99, P<0.001), but with no statistical difference between the laser and photodynamic groups ( χ2=0.82, P=0.366). Conclusions:CO 2 laser therapy and photodynamic therapy are effective treatments for cervical LSIL, significantly superior to follow-up observation in terms of lesion remission and HR-HPV clearance rates. Individualized treatment plans could be developed based on the patient′s age, duration of HR-HPV infection, colposcopic impression, and economic conditions.

Objective To investigate the effect of chemokine CXC ligand 9(CXCL9)on cognitive function impairment in patients with breast cancer brain metastases undergoing whole-brain radiotherapy(WBRT)using bioinformatics methods.Methods The mRNA of breast cancer brain metastases datasets GSE43837 and GSE12276 and Alzheimer's disease(AD)dataset GSE161199 were screened and downloaded from GEO database.Limma method and Venn diagrams were used to identify common differentially expressed genes(DEGs),and protein-protein interaction and functional prediction through GeneMANIA website assays were performed.A total of 42 patients with breast cancer brain metastases who first visited the Department of Radiotherapy at the First Affiliated Hospital of Hebei North University from January 2021 to January 2023 were selected.Patients were divided into normal cognitive function group and cognitive function impairment group based on cognitive status.Enzyme-linked immunosorbent assay(ELISA)was employed to detect serum CXCL9 levels one week before and three months after radiotherapy.The mini-mental state examination(MMSE)was used to assess patients'cognitive function.Results The DEGs from datasets GSE43837 and GSE12276 included PKP1,POLDIP2,SPAG5,ALDOC,PTPRZ1,PKIA,TLCD1,CPE,PMP22 and CXCL9.The DEGs from GSE161199 included RPS16,CD79A,LYPD3,RPL28,HBG2,RPL23AP7,TRNR,CXCL9.Venn diagram showed that CXCL9 was a common DEG between breast cancer brain metastasis and AD.Functional enrichment analysis indicated that CXCL9 was involved in cellular responses to chemokines,negative regulation of immune system processes,negative regulation of vascular morphogenesis,Toll-like receptor signaling pathway,nucleotide oligomerization domain(NOD)-like receptor signaling pathway,and JAK-STAT signaling pathway.Before radiotherapy,patients with cognitive function impairment and normal cognitive function accounted for 61.9%and 38.1%,respectively,with a statistically significant difference in MMSE scores[(24.53±2.19)vs.(28.89±1.36),P＜0.01].Compared with normal cognitive function group,patients with cognitive function impairment had a significantly increased number of brain metastases and significantly lower Karnofsky performance status(KPS)scores and serum CXCL9 levels(P＜0.05).Three months after radiotherapy,patients with cognitive function impairment and normal cognitive function accounted for 47.6%and 52.4%,respectively,with a statistically significant difference in MMSE scores[(25.16±1.98)vs.(28.18±1.08),P＜0.01].Compared with normal cognitive function group,patients with cognitive function impairment had significantly lower CXCL9 levels(P=0.003).In patients with normal cognitive function,CXCL9 levels were remarkably lower after radiotherapy compared to those before radiotherapy(P=0.009).Conclusions Patients with cognitive function impairment had significantly lower CXCL9 levels than those with normal cognitive function,and whole-brain radiotherapy may be related to a certain degree of reduction in CXCL9 levels.