[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。

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.

Objective To investigate the predictive value of preoperative combined detection of neutrophil-to-lymphocyte ratio (NLR) and prothrombin time-international normalized ratio to albumin ratio (PTAR) for early abdominal infection after liver transplantation. Methods Clinical data of 287 recipients who underwent liver transplantation at the Liver Transplant Center of Beijing Friendship Hospital, Affiliated to Capital Medical University, from January 2020 to April 2024 were retrospectively analyzed. The patients were divided into infection group (n=60) and non-infection group (n=227) based on whether abdominal infection occurred within 30 days after surgery. The distribution characteristics of pathogens and infection time in infected patients were analyzed. Spearman correlation analysis was used to assess the correlation between NLR, PTAR, Child-Pugh score and preoperative model for end-stage liver disease (MELD) score. Univariate and multivariate logistic regression analyses were performed to identify risk factors for abdominal infection. Receiver operating characteristic (ROC) curves were plotted for NLR, PTAR, and the combined prediction model to evaluate their predictive efficacy for abdominal infection after liver transplantation. Based on the cutoff value of the combined model, recipients were divided into low-risk and high-risk groups, and Kaplan-Meier analysis was used to compare the cumulative incidence of abdominal infection within 30 days after surgery between the two groups. Results Among the 287 recipients who underwent liver transplantation, 60 developed bacterial or fungal abdominal infections postoperatively. A total of 86 strains were isolated from infected patients, with Gram-negative bacteria accounting for 58%, Gram-positive bacteria for 36%, and fungi for 5%. Preoperative NLR and PTAR were positively correlated with Child-Pugh and MELD scores (all 1 > r > 0, P < 0.05). Logistic regression analysis showed that preoperative NLR, preoperative PTAR, postoperative ICU stay duration and postoperative biliary leakage were risk factors for abdominal infection within 30 days after surgery. The area under the curve (AUC) for NLR, PTAR, Child-Pugh score and MELD score were 0.771, 0.735, 0.650 and 0.741, respectively. The AUC for the combined NLR and PTAR prediction model was 0.824 (95% confidence interval: 0.763-0.885, P < 0.001), with a cutoff value of 0.168. Kaplan-Meier analysis showed that the cumulative incidence of abdominal infection within 30 days after surgery was lower in the low-risk group than in the high-risk group, with statistically significant difference (P < 0.001). Conclusions Preoperative NLR and PTAR are independent risk factors for abdominal infection within 30 days after liver transplantation. The combined prediction model of NLR and PTAR may effectively identify high-risk recipients for early abdominal infection after liver transplantation, providing basis for early intervention.

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 preliminarily evaluate the effects and analyze the influencing factors of continuous renal replacement therapy (CRRT) in severe burn patients complicated with acute kidney injury (AKI).Methods:This study was a retrospective case series study. From January 2010 to December 2020, 79 severe burn patients complicated with AKI who received CRRT and met the inclusion criteria were admitted to the First Affiliated Hospital of Army Medical University (the Third Military Medical University). The general data (the same below) of all patients were collected, including gender, age, body mass index, burn area, burn index, cause of injury, whether combined with inhalation injury, acute physiology and chronic health status evaluation Ⅱ (APACHE Ⅱ) score and sepsis-related organ failure assessment (SOFA) score on admission, admission time after burn, and time of AKI after admission. The total efficacy of CRRT, including overall effective rate, complete effective rate, partial effective rate, ineffective rate, and deterioration rate, creatinine, urea, cystatin C, and fluid overload rate before and after treatment, in-hospital mortality, predictive mortality based on Baux scoring model, the most common cause of death, and length of hospital stay were recorded. According to the effect of CRRT, the patients were divided into effective group (42 patients) and ineffective group (37 patients). The general information of patients, the time to initiate CRRT after the occurrence of AKI, the duration of CRRT, etiology of AKI, AKI stage before CRRT initiation, CRRT mode, anticoagulant type, and in-hospital mortality were compared between the two groups of patients. The independent influencing factors for CRRT in severe burn patients complicated with AKI were screened. According to the etiology of AKI, the patients were divided into prerenal group (22 patients) and renal group (57 patients). The general information of patients, the time to initiate CRRT after the occurrence of AKI, the duration of CRRT, and total efficacy of CRRT (except for the most common cause of death) were compared between the two groups of patients.Results:Among the 79 patients, 73 cases were male and 6 cases were female, with age of (46±14) years, body mass index of (24.0±2.9) kg/m 2, total burn area of (69±26)% total body surface area (TBSA), full-thickness burn area of (44±25)%TBSA, and burn index of 57 (36, 76). There were 36 cases of flame burns, 19 cases of electrical burns, 16 cases of hydrothermal burns, 6 cases of explosive burns, and 2 cases of chemical burns. Thirty-nine patients were complicated with inhalation injury. The APACHE Ⅱ score was 16 (12, 18) and the SOFA score was 11 (5, 13) on admission. The patients were admitted to the hospital on 0 (0, 2) d after burn, and AKI occurred on 0 (0, 6) d after admission. The overall effective rate of CRRT was 53.16% (42/79), the complete effective rate was 30.38% (24/79), the partial effective rate was 22.78% (18/79), the ineffective rate was 31.65% (25/79), and the deterioration rate was 15.19% (12/79). The creatinine and urea of patients after treatment were significantly lower than those before treatment (with Z values of -3.26 and -2.54, respectively, P<0.05); there were no statistically significant differences in the cystatin C and fluid overload rate of patients before and after treatment ( P>0.05). The in-hospital mortality of patients was 17.72% (14/79), and the predictive mortality based on Baux scoring model was 75.10% (18.94%, 91.84%). The most common cause of death was multiple organ failure, and the length of hospital stay was 39.43 (11.52, 110.58) d. There were statistically significant differences in the full-thickness burn area, the duration of CRRT, and etiology of AKI of patients between effective group and ineffective group (with Z values of -1.99 and -2.90, respectively, χ2=5.58, P<0.05). There were no statistically significant differences in the other indicators ( P>0.05). The etiology of AKI and full-thickness burn area were the independent influencing factors for CRRT in severe burn patients complicated with AKI (with odds ratios of 4.21 and 1.03, respectively, 95% confidence intervals of 1.20-14.80 and 1.00-1.05, respectively, P<0.05). There were statistically significant differences in the cause of injury, overall effective rate of CRRT, total burn area, burn index, admission time after burn, time of AKI after admission, the time to initiate CRRT after the occurrence of AKI, and predictive mortality based on Baux score model of patients between prerenal group and renal group (with χ2 values of 12.59 and 5.58, respectively, Z values of 2.46, 2.43, -2.43, -4.03, -3.01, and -2.31, respectively, P<0.05). Before treatment, urea and cystatin C of patients in renal group were significantly higher than those in prerenal group (with Z values of -2.98 and -2.77, respectively, P<0.05), and the liquid overload rate was significantly lower than that in prerenal group ( Z=-2.99, P<0.05); after treatment, the cystatin C of patients in renal group was significantly higher than that in prerenal group ( Z=-2.08, P<0.05); there were no statistically significant differences in the other indicators ( P>0.05). Conclusions:CRRT can significantly improve renal function, avoid fluid overload, and alleviate renal injury in severe burn patients complicated with AKI. Prerenal AKI is the main independent influencing factor leading to ineffective CRRT.

The 19 th Chinese Symposium of Burns and Wounds was successfully held in Foshan of Guangdong Province from June 20 th to 22 nd in 2024. There were more than 700 delegates attending the academic event. The theme of the congress was expansion, integration and standardization, which could promote academic exchanges, multi-disciplinary fusion, and standardization of clinical treatment of burns and wounds. A total of nearly 200 famous experts and scholars had their speeches on the two-day keynote forum and special academic seminars including critical care, wound repair, scar prevention and treatment, rehabilitation nursing, and disciplinary integration sessions. The congress ended successfully with abundant fruits and friendship.

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 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: 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 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.