Salvia miltiorrhiza (S. miltiorrhiza) represents a crucial component of traditional Chinese medicine, demonstrating effects on blood circulation activation and stasis removal, and has been widely utilized in asthma treatment. This study isolated a novel phenolic acid (S1) from S. miltiorrhiza and investigated its anti-asthmatic activity and underlying mechanisms for the first time. An allergic asthma (AA) model was established using ovalbumin (OVA). The mechanism of S1's effects on AA was investigated using multi-factor joint analysis, flow cytometry, and co-culture systems to facilitate clinical asthma treatment. S1 (10 or 20 mg·kg^-1) was administered daily to mice with OVA-induced AA (OVA-AA) during days 21-25. The study examined airway responsiveness, lung damage, inflammation, and levels of immunoglobulin E (IgE), PGD2, interleukins (IL-4, 5, 10, 13, 17A), tumor necrosis factor α (TNF-α), GM-CSF, CXCL1, CCL11, and mMCP-1. Additionally, mast cell (MC) activation and degranulation were explored, along with T helper type 17 (Th17)/Treg immune cells and TLR4 pathway biomarkers. The antagonistic activity of that specific antagonist of TLR4 (TAK-242) (1 µmol·L^-1), a specific TLR4 blocker, against S1 (10 µmol·L^-1) was examined in co-cultured 16HBE cells and bone marrow-derived cells (BMDCs) or splenic lymphocytes (SLs) induced with LPS (1 µg·mL^-1) to elucidate the TLR4 pathway's mediating role. S1 demonstrated reduced airway responsiveness, lung damage, and inflammation, with downregulation of IgE, PGD2, interleukins, TNF-α, GM-CSF, CXCL1, CCL11, and mMCP-1. It also impeded MC activation and degranulation, upregulated IL-10, and influenced Th17/Treg immune cell transformation following OVA challenge. Furthermore, S1 inhibited the TLR4 pathway in OVA-AA mice, and TLR4 antagonism enhanced S1's positive effects. Analysis using an OVA-AA mouse model demonstrated that S1 alleviates AA clinical symptoms, restores lung function, and inhibits airway response. S1's therapeutic effects occur through regulation of Th17/Treg immune cells and inflammation, attributable at least partially to the TLR4 pathway. This study provides molecular justification for S1 in AA treatment.

Cancer-associated thromboembolism(CAT)is one of the most common complications and the second direct cause of mortality in patients with malignant tumors,which seriously affect patients'life quality and prognosis.In recent years,with the deepening of mechanism researches of cancer and thrombosis,treatment strategies of CAT were also improved.The current status and progresses of clinical treatment of CAT were reviewed in this article.

Objective:To investigate the clinical efficacy of oblique intervertebral fusion in the treatment of failed internal fixation of thoracolumbar fractures.Methods:A retrospective study was conducted to analyze the clinical data of 14 patients who had undergone revision surgery for failed internal fixation of thoracolumbar fracture at Department of Orthopedics, The First Hospital Affiliated to Zhengzhou University from January 2014 to December 2021. There were 6 men and 8 women with a mean age of 47.5 (42.0, 54.3) years. Fracture segments: T 12 in 2 cases, L 1 in 3 cases, L 2 in 4 cases, L 3 in 3 cases, and L 4 in 2 cases; AO classification: type A in 1 case, type B in 7 cases, and type C in 6 cases. Their prior surgical method was posterior internal fixation with pedicle screws. The revision surgery consisted of subtotal vertebral resection through the oblique lateral approach, bone column reconstruction and lateral screw-rod internal fixation for intervertebral fusion after posterior internal fixation reset. The operation time, intraoperative bleeding, postoperative hospital stay, and incidence of complications were recorded. Compared were visual analogue scale (VAS) and Oswestry disability index (ODI) scores for low back pain at preoperation, 3 days and 3 months postoperation, and the last follow-up, fusion at the last follow-up, and Frankel grading for neurological function at preoperation and postoperation. Results:All the 14 patients underwent surgery successfully and were followed up for 23 (18, 24) months. The operation time was (175.1±28.2) min, the intraoperative bleeding (300.4±122.6) mL, and the postoperative hospital stay 6 (6, 7) d. One case developed postoperative transient hip flexion weakness but was discharged after restoration of normal muscle strength by conservative treatment. Both VAS and ODI scores for low back pain at all postoperative time points were significantly improved compared with the preoperative values ( P<0.05), with a significant trend of 3 days postoperation >3 months postoperation > the last follow-up ( P<0.05). In the 12 patients with preoperative neurological damage, the Frankel grading rose by at least 1 level postoperatively ( Z=-3.110, P=0.002). The last follow-up revealed no loosening or fracture of the internal fixation. Complete bony fusion was visible in all CT sagittal reconstructions. Conclusion:For patients with thoracolumbar fracture undergoing failed internal fixation, oblique intervertebral fusion is an alternative minimally invasive surgical treatment due to its satisfactory overall outcomes.

Objective:To investigate the value of a nomogram predicting the outcome of intracerebral hemorrhage (ICH) based on clinical characteristics and diffusion-weighted imaging (DWI) of hyperintense lesions.Methods:A case-control study. Consecutive patients, aged 30-88(59±13) years old, with ICH were recruited at the Stroke Center of Zhengzhou People′s Hospital from January 2018 to August 2021. Patients were divided into a group with DWI lesions and a group without DWI lesions depending on whether there were DWI hyperintense lesions distant from the hematoma. Prognosis was evaluated at 90 days via the modified Rankin Scale (mRS). Univariate and multivariable logistic regression models were used to identify independent predictors of a poor ICH outcome (mRS score≥4), and a nomogram model was developed. The performance of the nomogram was validated via the area under the receiver operating characteristic curve (AUC) and a calibration chart.Results:Of the 303 patients included in the study, 24.8% presented with DWI lesions; 17.5% with asymptomatic DWI lesions and 7.3% with symptomatic DWI lesions. Poor outcomes were significantly more frequent in the group with DWI lesions than in the group without DWI lesions ( χ2=21.32, P<0.001). In multivariable regression analysis, age [odds ratio ( OR)=1.032, 95% confidence interval ( CI) 1.002-1.063, P=0.035], hematoma volume ( OR=1.050, 95% CI 1.011-1.090, P=0.012), hematoma location ( OR=3.839, 95% CI 1.248-11.805, P=0.019), DWI lesions ( OR=3.955, 95% CI 1.906-8.206, P<0.001), and baseline NIHSS scores ( OR=1.102, 95% CI 1.038-1.170, P=0.001) were independent predictors of a poor outcome. In subgroup analysis patients with asymptomatic DWI lesions had a 3-fold greater risk of a poor outcome compared to those without DWI lesions ( OR=3.135, 95% CI 1.382-7.112, P=0.006), and patients with symptomatic DWI lesions had a 7-fold greater risk of a poor outcome compared to those without DWI lesions ( OR=7.126, 95% CI 2.279-22.277, P=0.001). A nomogram model was established based on the independent predictors for a poor outcome. The AUC of the nomogram was 0.846 (95% CI 0.795-0.898), and a calibration chart indicated good consistency between values predicted by the nomogram and actual observed values. Conclusions:DWI lesions are an independent risk factor for a poor outcome in patients with ICH-particularly symptomatic DWI lesions. A nomogram model based on clinical characteristics and DWI lesions exhibited good efficacy when predicting the outcome of ICH.

Cerebrovascular disease is one of the leading causes of death and disability across the world. Vascular homeostasis and recovery is critical to the body. Klotho is an important endogenous pleiotropic protein involved in a variety of pathophysiological processes,such as aging and calcium and phosphorus metabolism,which is closely associated with vascular disease. Recent clinical studies have demonstrated close links between low Klotho levels and various risk factors for cerebrovascular disease,suggesting that Klotho has the potential of predicting the risk of ischemic and hemorrhagic cerebrovascular diseases and poor prognosis. Basic studies have also shown that Klotho plays a crucial role in the maintenance of vascular homeostasis. Klotho can promote the production of nitric oxide,inhibit the expression of inflammatory factors,and mediate antioxidant and anti-aging effects,which can delay atherosclerosis and vascular calcification. Therefore,Klotho may serve as a new target for the prevention and treatment of cerebrovascular disease. This review provides an overview of the relationship between Klotho and cerebrovascular disease and its potential biological mechanisms.

Objective:To investigate the associations between small diffusion-weighted imaging (DWI) hyperintensities lesions and total cerebral small vessel disease (cSVD) burden and the influence on prognosis in patients with acute intracerebral hemorrhage (ICH).Methods:Consecutive patients with acute spontaneous ICH from January 2018 to June 2021 were recruited in the Stroke Center of Zhengzhou People′s Hospital. Magnetic resonance imaging was performed to quantify DWI hyperintensities lesions and cSVD imaging markers, including white matter hyperintensities, enlarged perivascular spaces, lacunes and cerebral microbleeds, which were calculated for the total cSVD burden (0-4 points). The prognosis was assessed with the modified Rankin Scale (mRS) at discharge and 90-day. Multivariable Logistic regression models were adopted to explore the associations between DWI lesions and total cSVD burden and clinical outcome.Results:Of 283 included patients, 59 (20.8%) had small DWI lesions, 32 (11.3%) had multiple lesions. They were mostly punctate, mainly located in the cortical and subcortical regions, and scattered in multiple vascular territories. With the increase of cSVD burden, the number of DWI lesions gradually increased. Spearman correlation analysis showed that the total cSVD burden was positively correlated with the number of DWI lesions ( r=0.21, P<0.001). In multivariable regression analyses, the total cSVD burden was independently associated with DWI lesions ( OR=1.63, 95% CI 1.23-2.15, P=0.001). The 90-day poor outcome (mRS scores≥4) in patients with DWI lesions was significantly higher than those without DWI lesions (39.3% vs 16.3%, χ 2=14.38, P<0.001), while there was no statistically significant difference in the poor outcome of discharge between the two groups (26.5% vs 17.7%, χ 2=3.06, P=0.080). With the increase in the number of DWI lesions, the 90-day poor outcome increased significantly (trend chi-squared test χ 2=11.50, P=0.001). Multivariable analyses showed that DWI lesions ( OR=4.39, 95% CI 1.92-10.03, P<0.001) and their number ( OR=1.42, 95% CI 1.06-1.90, P=0.018) were independently associated with the 90-day poor outcome. Conclusions:Higher total cSVD burden is an independent risk factor for small DWI lesions in patients with ICH. Small DWI lesions were independently associated with the 90-day poor outcome, but not with the discharge outcome.

With the rapid development of radiotherapy equipment, imaging technology, and artificial intelligence, radiotherapy has entered the era of precision therapy. Radiotherapy is one of the important methods for the treatment of pancreatic cancer, and rapid progress has been made in related concepts and technical models of radiotherapy in recent years. With reference to the latest advances in radiotherapy technology and the change of radiotherapy dose mode, which the experts in the field of radiotherapy are concerned with, this article reviews and analyzes recent articles and points out that multimodal images play an important role in guiding radiotherapy for pancreatic cancer, and the dose mode of radiotherapy develops to high-dose hypofractionated radiotherapy. The effect of neoadjuvant radiotherapy has been further confirmed, and strong chemotherapy with the combination of multiple drugs is the main radiotherapy regimen for pancreatic cancer.

Radiotherapy plays an important role in the treatment of all stages of pancreatic cancer, and some therapeutic effects have been obtained. At present, it needs to be considered and practiced in many aspects that how to play the role of radiotherapy in the treatment of pancreatic cancer. It is related to the choice of dose mode, the accuracy of irradiation, the cooperation of other treatment methods and other factors. The emergence of precision radiotherapy technology and the subsequent change in the idea of radiotherapy will further improve the role of radiotherapy in the treatment of pancreatic cancer. Based on the relevant literatures at home and abroad and our own experience, this paper reviews the role of precision radiotherapy for pancreatic cancer.

Objective:To disclose the expression and correlation of E6, E7 and PD-L1 in cervical squamous cell carcinoma (CSCC) tissues and explore the immune regulation of E6, E7 on PD-L1.Methods:The expressions of E6, E7 and PD-L1 in human papillomavirus (HPV) negative normal cervical tissue, cervical intraepithelial neoplasia (CIN) tissue and HPV16, 52 and 58 positive CSCC tissue were detected by Western blot (WB). HPV16 positive CSCC and HPV negative CSCC tissues were used for primary cell isolation, identification and culture. E6, E7 small interfering RNAs (siRNAs) were constructed and transfected into HPV16 positive CSCC cells via liposomes.The expression of PD-L1 in the cells was detected by WB. Plasmids of E6, E7 gene were constructed and overexpressed in HPV negative CSCC cells to detect the expression of PD-L1.Results:The expression of E6, E7 and PD-L1 was not detected in the HPV negative normal cervical. While in the HPV16, 52, 58 positive CSCC tissue group, the expression of all the three were significantly higher than that in the CIN group ( P<0.01). Primary HPV16 positive CSCC and HPV negative CSCC cells were successfully isolated and cultured, which were named as H16CC cell lines and HNCC cell lines respectively. After inhibiting the expression of E6, E7 in H16CC cell lines, the expression of PD-L1 was significantly decreased ( P<0.05). The expression of PD-L1 was significantly increased after the overexpression of E6, E7 in HNCC cell lines ( P<0.05). Conclusions:The expression of PD-L1 is positively correlated with E6, E7, which may regulate the occurrence and development of CSCC by mediating the immune escape mechanism of PD-L1 in CSCC.

Objective: To explore the correlation between microdamage in white matter and radiotherapy dose at early stage after radiotherapy (RT) in patients with nasopharyngeal carcinoma (NPC). Methods: Thirty-three patients who were initially diagnosed with NPC were recruited and received diffusion tensor imaging (DTI) scan and neuro-cognitive scale test within 1 week before RT and the first day after RT. DTI-related characteristic parameters including fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (λ_‖), and radial diffusivity (λ_⊥) were calculated based on whole-brain voxel analysis method. Paired t-test was conducted to evaluate statistical significance between pre-RT and post-RT groups. In the subgroup analysis, all the subjects were divided into 3 groups according to the average dose of temporal lobe, and each group was set with an equal dose interval range. The DTI-related parameters of whole brain pre-RT and post-RT in each group were statistically compared. All the statistical results were corrected by FDR with a threshold of P<0.05 and clusters>100. Results: FA, MD, λ_‖ and λ_⊥in the post-RT group significantly differed compared with those in the pre-RT group (P<0.05). The values of FA, MD, λ_‖ and λ_⊥were 0.455±0.016, (9.893±0.403)×10^-4, (13.441±0.412)×10^-4 and (8.231±0.429)×10^-4, respectively. Subgroup analysis showed that the extent and degree of λ_‖ and λ_⊥ changes were exacerbated with the increase of the average dose of temporal lobe after RT. Particularly in high-dose group, the average dose range was 25-35 Gy and the extent of regions with significant changes was significantly larger than those in the medium-dose (15-25 Gy) and low-dose groups (5-15 Gy)(P<0.05). Conclusions DTI can be utilized to detect" normal" brain tissue microdamage in NPC patients at early stage after RT. The average radiation dose of temporal lobe may be one of the reasons for the severity of cerebral microdamage. In the future, DTI technique may be useful for guiding exposure dose of organs at risk during RT planning and to evaluate the cohort with a high risk of cerebral microdamage at early stage after RT, thereby protecting normal cerebral tissues to the maximum extent.