Stroke is the main cause of death and disability among adults in China and is characterized by high incidence， disability， mortality， and recurrence rates. The combination of traditional Chinese and Western medicine has great potential in treating stroke and its sequelae. The classic traditional Chinese medicine prescription Da Chengqitang （DCQT） has a long history and proven efficacy in treating stroke. Clinically， DCQT is often used to treat stroke and its sequelae. However， the number and quality of clinical trials of DCQT in treating stroke need to be improved. Because of the insufficient basic research， the active ingredients and multi-target mechanism of action of DCQT remain unclear. Our research group has previously confirmed that DCQT can effectively reverse neurological damage， reduce iron deposition， and downregulate the levels of pro-inflammatory cytokines in the rat model of hemorrhagic stroke. The treatment mechanism is related to the nuclear factor erythroid 2-related factor 2 （Nrf2）-mediated signaling pathway and p38 mitogen-activated protein kinase （MAPK） signaling-mediated microglia activation. To clarify the pharmacodynamic basis and anti-stroke mechanism of DCQT， this article reviews the research progress in the treatment of stroke with DCQT in terms of clinical trials， pharmacodynamic material basis， safety evaluation， and mechanisms of absorbed components. This article summarizes 45 major phytochemical components of DCQT， 11 of which are currently confirmed absorbed components. Among them， emodin， rhein， chrysophanol， aloe-emodin， synephrine， hesperidin， naringin， magnolol， and honokiol can be used as quality markers （Q-markers） of DCQT. The mechanism of DCQT in treating stroke is complex， involving regulation of inflammatory responses， neuronal damage， oxidative stress， blood-brain barrier， brain-derived neurotrophic factor， and anti-platelet aggregation. This article helps to deeply understand the pharmacodynamic basis and mechanism of DCQT in treating stroke and provides a theoretical basis for the clinical application of DCQT in treating stroke and the development of stroke drugs.

[摘 要] 可变剪接是转录后水平的基因表达调控机制，也是导致真核生物转录组和蛋白质组多样性的重要途径。然而，可变剪接的异常是驱动肿瘤进展的重要推手。在肿瘤微环境中，肿瘤细胞、免疫细胞及肿瘤中其他类型细胞中mRNA的异常剪接，不仅参与塑造肿瘤细胞的恶性生物学行为和免疫逃逸，还促进支持肿瘤进展的免疫抑制性微环境的形成。靶向肿瘤相关剪接体组分、剪接调控因子、可变剪接产生的蛋白异构体和mRNA变异体，以及异常可变剪接产生的肿瘤新抗原已成为肿瘤治疗的新策略，已有基于可变剪接的肿瘤生物治疗项目进入到Ⅰ期临床研究阶段。基于可变剪接的肿瘤治疗面临安全性、长读测序和算法优化、核酸类药物递送等许多尚待解决的科学和技术问题，这些挑战的解决将为精准筛选肿瘤相关靶点和高免疫原性新抗原，突破传统疗法耐药瓶颈，增强免疫检查点阻断和CAR-T细胞等疗效提供新策略，开辟新领域。

Objective: To elucidate the differences in manual acupuncture effectiveness at sensitized points by investigating the mechanisms of local skin action at different sensitization points in rats with knee osteoarthritis (KOA). Methods: Forty Sprague–Dawley rats were equally divided into control, model (1 mg of monoiodoacetate into the right knee joint cavity), sham operation, manual acupuncture at right Tianjing acupoint (MAR-SJ 10), and left SJ 10 groups. Safranine-O and fast green staining were used to assess the modeling. The morphological and functional changes in mast cells (MCs) were assessed during acupoint sensitization using toluidine blue and immunofluorescence staining. The levels of serotonin, histamine, substance P (SP), and tryptase at skin acupoints and serum levels of IL-β, IL-6, and TNF-α were detected using ELISA. Results: After 14 days of treatment, the number of MCs and their degranulation rates were statistically higher in the model group than in the control group (both P < .001). After applying acupuncture, the levels of 5-HT, HA, and SP at skin acupoints were lower than those in the model group (all P < .05), and tryptase level was higher (both P < .05). Tryptase level was higher on the skin at the MAL-SJ 10 acupoint than that on the MAR-SJ 10 acupoint (P = .004). Compared with the model group, the serum levels of IL-1β, IL-6, and TNF-α in the MAR-SJ 10 and MAL-SJ 10 groups were lower (all P < .05). Conclusion Acupuncture at KOA-sensitized acupoints mitigates joint injury in KOA rats and may bidirectionally regulate local MCs of these acupoints. This finding not only enhances the reference value of sensitizing points in clinical diagnosis and treatment, but also contributes to the understanding of the biological mechanisms underlying acupuncture intervention at sensitizing points.

Objective:To explore the brain activation intensity changes of depressed patients in the phase of expected value (EV), positive prediction error (+ PE) and negative prediction error (-PE) under uncertain (risky, ambiguous) decision-making.Methods:From July 2018 to February 2021, a total of 48 depressed patients in the Affiliated Hospital of Qingdao University were collected (depression group), and 69 sex-, age-, and educational level-matched healthy people were recruited as the control group. All participants completed risky and ambiguous decision-making tasks under the E-Prime system.SA-9800 brain functional audio-visual stimulation system and GE3.0 T functional magnetic resonance imaging (fMRI) scanners were used to conduct synchronous scanning and data acquisition. Using Xjview software to analyze the activation intensity of related brain areas to compare the activity intensity of the two groups.SPSS 16.0 software was used for chi square test, independent sample t-test. Results:Under risky decision-making, compared with the control group, the brain areas with reduced activation during EV phase in depression group were bilateral prefrontal cortex (PFC)(MNI coordinate: left x=-45, y=21, z=-6; right x=0, y=69, z=-3), left para hippocampal gyrus(PHG)(MNI coordinate: x=-9, y=0, z=-22), bilateral occipital lobe(OL)(MNI coordinate: left x=-51, y=-81, z=-3; right x=48, y=-84, z=-9)( P<0.05). The brain areas with reduced activation during + PE phase were bilateral PFC, left hippocampus (HIP), bilateral temporal lobe (TL), left middle occipital gyrus( P<0.05). The brain areas with reduced activation were bilateral PFC, right putamen, bilateral TL( P<0.05) during -PE phase. Under ambiguous decision-making, compared with the control group, the brain areas with reduced activation during EV phase in depression group were bilateral PFC, right OL( P<0.05); the brain areas with reduced activation during + PE phase were bilateral PFC, right putamen and hippocampus, bilateral TL, bilateral OL( P<0.05); and the brain areas with reduced activation were bilateral PFC, bilateral TL( P<0.05) during -PE phase. Conclusion:The study shows that the activities of reward brain areas such as PFC, limbic system and OL system are reduced during EV and PE phase under uncertain decision-making in depressed patients.

Objective Pertussis cases have increased markedly since 2018 in Guangxi.The aim of this study was to evaluate antibody levels and the infection status of pertussis in the resident population. Method A total of 10,215 serum samples from residents were collected from August-November 2018 and tested for anti-pertussis IgG and toxin IgG using the enzyme-linked immunosorbent assay(ELISA). Results Of the collected samples,1,833(17.94%)tested positive for anti-pertussis IgG,with the median concentration of 16.06 IU/mL.Antibody level<10 IU/mL accounted for more than 60%in children under 4 years of age,but declined with age,whereas the percentages of the other three levels(10-40,40-50,and≥50 IU/mL)increased almost with age(P<0.001).Moreover,7,924 samples were selected for anti-pertussis toxin IgG,of which 653(8.24%)tested positive(≥40 IU/mL)with the median concentration of 5.89 IU/mL,and 204 participants(2.56%)had recent pertussis infection(≥100 IU/mL).Among the different age groups,the highest rates of positivity and recent infection were observed at 11-20 years of age,the lowest positivity rate at 5 years of age,and the lowest recent infection rate at 4 years of age(P<0.001,P=0.005,respectively). Conclusion The survey results showed that all age groups in Guangxi lacked immunity against pertussis,which was one of the main factors contributing to the resurgence of pertussis in 2018.In addition,the prevalence of pertussis is relatively high in Guangxi,and its incidence is seriously underestimated,especially in adolescents and adults.

Objective:To analyze the safety of reduced clinical target volume (CTV) irradiation of suspicious positive lymph nodes in IIa region in patients with N 0-N 1 nasopharyngeal carcinoma (NPC) and the protective effect of submandibular gland and long-term resting dry mouth, and to explore the diagnostic value of multimodal imaging for suspicious cervical lymph nodes. Methods:Clinical data of T 0-4N 0-1M 0 stage NPC patients admitted to Jiangsu Cancer Hospital from July 2015 to April 2017 were retrospectively analyzed. Clinical, radiation therapy planning, multimodal imaging and other relevant data were collected. All patients were treated with an optimized regimen of IMRT with a prophylactic radiation dose of 50.4 Gy (named as CTV50) for IIa region. Imaging characteristics and treatment response of suspicious lymph nodes were monitored by MRI, MRI-DWI, PET-CT and repeated enhanced positioning CT, etc. The dosimetry of the submandibular gland between optimized and standard dose plans (CTV50 vs. CTV60) was compared by paired t-test. The long-term dry mouth degree of the patients was evaluated using advanced radiation injury from Radiation Therapy Oncology Group (RTOG), Jiangsu Cancer Hospital Multi-dimensional Dry Mouth Evaluation Scale and summated xerostomia inventory (SXI). The difference of dry mouth degree was analyzed by rank-sum test. Results:A total of 106 patients were included in this study, including 149 cervical lymph node negative sides, 73 sides of which had ≤3 recognizable lymph nodes, and 76 of which were>3 in Ⅱa region. Among patients with N 1 stage, 63 patients underwent contralateral single neck area optimization, and 43 patients (N 0 stage and N 1 stage patients with retropharyngeal lymph node metastasis) underwent double-neck area optimization. A total of 109 suspicious lymph nodes with a short diameter of >5 mm were found on the largest cross section, of which 105 had clear portal structure. The ratio of long to short diameter was ≥1.5 in 93 cases, and the maximum standardized uptake value (SUV max) in PET-CT was ≥2.5 in 76 cases. No lymph node recurrence was found in the CTV optimized area. There was no significant difference in the average dose of GTV in tumor target area after optimization ( P>0.05), and the D mean and V 39 Gy in submandibular gland were significantly lower than those in unoptimized plan (both P<0.01). There was no significant difference in long-term dry mouth and resting dry mouth between patients with unilateral and bilateral optimization of submandibular gland (both P>0.05). Conclusions:The optimal program of CTV50 reduction irradiation in Ⅱa area of N 0-N 1 NPC patients is safe and effective. The submandibular gland has obvious dosimetric advantages, and patients have a good subjective response to resting dry mouth. The multimodal imaging tools such as enhanced CT, MRI-DWI and PET-CT should be performed to deliver individual evaluation and treatment for suspicious lymph nodes.

Objective:To investigate the impact of elevated glucose-induced RNA oxidation on pancreatic β-cell function, activity, and underlying molecular mechanisms.Methods:Rat pancreatic islet β-cell tumour INS-1 cells were cultured in vitro and subjected to nucleic acid oxidation assessment using isotope dilution ultra-high performance liquid tandem mass spectrometry(ID LC MS/MS)following high glucose exposure.In vitro simulation of increased RNA oxidation in INS-1 cells was achieved using 8-oxoguanosine-5'-triphosphate(8-oxoGTP).Cell proliferation was evaluated through CCK-8 assay, apoptosis was measured via flow cytometry, and gene expression of insulin(INS), pancreatic-duodenal homologous cassette 1(PDX1), cysteine-aspartate proteinase 3(Casp3), and cysteine aspartate protease 6(Casp6)was analyzed at the mRNA level.Additionally, whole transcriptome sequencing was performed to elucidate the molecular mechanisms underlying the impact of RNA oxidation on INS-1 cells.Results:Elevated glucose levels induced an increase in RNA oxidation within INS-1 cells.This heightened RNA oxidation led to the inhibition of INS-1 cell proliferation, a reduction in mRNA levels of INS and PDX1 genes, and the promotion of apoptosis-related casp3 and casp6 gene mRNA synthesis.Transcriptome sequencing analysis unveiled that the elevated RNA oxidation caused differential expression of mRNA, lncRNA, miRNA, and circRNA in INS-1 cells.This included a significant down-regulation of transcription factors such as Mafa, Pdx1, Pax6, and Mnx1, alongside an up-regulation of various miRNAs like rno-miR-124-3p, rno-miR-133a-3p, rno-miR-3120, rno-miR-212-3p, and rno-miR-7a-2-3p.These molecular changes contributed to the altered expression of associated lncRNAs, ultimately hindering insulin synthesis and secretion, as well as β-cell proliferation.Conclusions:Increased RNA oxidation down-regulates the levels of key β-cell transcription factor mRNAs, contributes to the differential expression of related non-coding RNAs(ncRNAs), particularly lncRNAs, impacts β-cell insulin synthesis and secretion, hinders cell proliferation, and serves as a significant factor in β-cell dysfunction and decreased activity in type 2 diabetes mellitus(T2DM).

Objective To differentiate cerebral parenchymal hemorrhage from contrast extravasation based on the imaging characteristics of a high-density shadow within the brain parenchyma,which is demonstrated on early(within 24 hours)plain CT scan in patients with acute ischemic stroke after receiving mechanical thrombectomy(MT).Methods The clinical data of 77 patients with ischemic stroke caused by acute large-vessel occlusion,who received MT and whose early plain CT scan(performed within 24 hours after MT)showed a high-density shadow within the brain parenchyma,were retrospectively analyzed.According to the results of CT reexamination performed at 24-48 hours after treatment,the patients were divided into parenchymal hemorrhage group(n=38,43 sites)and pure contrast extravasation group(n=39,47 sites).The direct signs(including location distribution,maximum CT value,volume,mixed density sign)and the indirect signs(including local space-occupying effect,intraventricular high density,subarachnoid high density)of the post-thrombectomy intraparenchymal high-density(PTIH)shadow displayed on early CT images after MT were analyzed.The differences in imaging characteristics between the two groups were analyzed by using t-test,Mann-Whitney rank sum test,chi-square test,Fisher exact test and multivariate logistic regression analysis.Results The space-occupying effect(28/38 versus 9/39,P=0.003)and intraventricular high density lesion(5/38 versus 0/39,P=0.025)were more likely to occur in the parenchymal hemorrhage group than in the pure contrast extravasation group.The newly-developed 90 PTIH lesions included 43 parenchymal hemorrhage foci and 47 contrast extravasation foci.Multivariate logistic regression analysis showed that the differences in the PTIH volume and mixed density sign between the two groups were statistically significant(both P＜0.05,OR=2.93 and OR=9.24 respectively).The optimal critical value of PTIH volume for diagnosing cerebral parenchymal hemorrhage was 9.3 cm3.Conclusion The space-occupying effect and intraventricular high density are the indirect signs for judging a newly-developed PTIH to be a cerebral parenchymal hemorrhage.PTIH volume ≥9.3 cm3 and mixed density sign are the direct signs for judging a newly-developed PTIH to be a cerebral parenchymal hemorrhage.

Objective To evaluate the impact of the growth speed of cerebral infarction on the occurrence of symptomatic intracranial hemorrhage(sICH)in patients with acute anterior circulation ischemic stroke after mechanical thrombectomy.Methods The clinical data of patients with acute ischemic stroke(AIS),who received mechanical thrombectomy at the First Affiliated Hospital of Soochow University of China from June 2016 to December 2022,were retrospectively analyzed.After thrombectomy,the patients were divided into sICH group and non-sICH group according to Heidelberg criteria.The clinical data and imaging findings were compared between the two groups.Multivariate logistic regression analysis was used to identify the independent risk factors for sICH after thrombectomy,and the area under the receiver operating characteristic curve(AUC)was used to evaluate the efficacy of the growth speed of cerebral infarction in predicting sICH.Results A total of 218 patients were enrolled in this study,sICH group had 23 patients and non-sICH group had 195 patients.The differences in NIHSS score,collateral circulation status,core infarction volume,and growth speed of cerebral infarction between the two groups were statistically significant(all P＜0.05).Multivariate logistic regression analysis showed that rapid growth speed of cerebral infarction was an independent risk factor for sICH occurring after mechanical thrombectomy.For predicting sICH,the sensitivity and specificity of the growth speed of cerebral infarction were 78.3％and 69.7％respectively,with an AUC of 0.751 and a predicted value of 7.6 mL/h.Conclusion The rapid growth speed of cerebral infarction is a predictive factor for sICH occurring after mechanical thrombectomy in patients with acute anterior circulation ischemic stroke.The risk of sICH becomes higher after mechanical thrombectomy when the growth speed of cerebral infarction is faster than 7.6 mL/h.

Objective To evaluate the clinical effect of intraoperative ultra-early mild hypothermia on severe spontaneous intracerebral hemorrhage.Methods A total of 71 cases of severe spontaneous intracere-bral hemorrhage admitted and treated in the neurosurgery department of this hospital from January 2021 to June 2023 were included,in which 35 cases were in the intraoperative ultra-early mild hypothermia treatment group (the study group),36 cases were in the postoperative mild hypothermia treatment group (the control group).The venous blood samples were collected immediately after operation end,at 6,24,72 h and on 7 d af-ter operation for detecting the C-reactive protein (CRP) and interleukin-6 (IL-6) levels.The national institu-tes of health stroke scale (NIHSS) scoring and the Glasgow Outcome Scale (GOS) scoring in the two groups were conducted in postoperative 3 months.The independent sample t test was used to analyze the differences in CRP,IL-6 and NIHSS score between the two groups and the chi square test was adopted to analyze the good prognosis rate of the two groups.Results There was no statistically significant difference in serum CRP and IL-6 levels immediately after operation between the two groups (P>0.05),but the serum CRP and IL-6 lev-els at 6,24,72 h,7 d after operation in the study group were lower than those in the control group,and the differences were statistically significant (P<0.05).The NIHSS in postoperative 3 months in the study group was lower that that in the control group,while the prognosis good rate in postoperative 3 months was higher than that in the control group,and the differences were statistically significant (P<0.05).Conclusion The intraoperative ultra-early mild hypothermia treatment for severe spontaneous intracerebral hemorrhage has better clinical effect than postoperative mild hypothermia.