Intraoperative cell salvage (IOCS) has been widely applied as an important blood conservation measure in surgical operations. However, there is currently a lack of clinical practice guidelines for the implementation of IOCS in patients with malignant tumors. This report aims to provide clinicians with recommendations on the use of IOCS in patients with malignant tumors based on the review and assessment of the existed evidence. Data were derived from databases such as PubMed, Embase, the Cochrane Library and Wanfang. The guideline development team formulated recommendations based on the quality of evidence, balance of benefits and harms, patient preferences, and health economic assessments. This study constructed seven major clinical questions. The main conclusions of this guideline are as follows: 1) Compared with no perioperative allogeneic blood transfusion (NPABT), perioperative allogeneic blood transfusion (PABT) leads to a more unfavorable prognosis in cancer patients (Recommended); 2) Compared with the transfusion of allogeneic blood or no transfusion, IOCS does not lead to a more unfavorable prognosis in cancer patients (Recommended); 3) The implementation of IOCS in cancer patients is economically feasible (Recommended); 4) Leukocyte depletion filters (LDF) should be used when implementing IOCS in cancer patients (Strongly Recommended); 5) Irradiation treatment of autologous blood to be reinfused can be used when implementing IOCS in cancer patients (Recommended); 6) A careful assessment of the condition of cancer patients (meeting indications and excluding contraindications) should be conducted before implementing IOCS (Strongly Recommended); 7) Informed consent from cancer patients should be obtained when implementing IOCS, with a thorough pre-assessment of the patient's condition and the likelihood of blood loss, adherence to standardized internally audited management procedures, meeting corresponding conditions, and obtaining corresponding qualifications (Recommended). In brief, current evidence indicates that IOCS can be implemented for some malignant tumor patients who need allogeneic blood transfusion after physician full evaluation, and LDF or irradiation should be used during the implementation process.

PURPOSE: Traumatic brain injury (TBI) is a significant public health issue that impacts individuals all over the world and is one of the main causes of mortality and morbidity. Decompressive craniectomy is the usual course of treatment. Basal cisternostomy has been shown to be highly effective as an alternative procedure to decompressive craniectomy. METHODS: We conducted a retrospective cohort of patients who received surgery for severe TBI between January 2019 and March 2023. Inclusion criterias were patients between the ages of 18 and 70 years who met the diagnostic criteria for severe TBI at first presentation and who underwent surgical intervention. The exclusion criteria were patients who have severe multiple injuries at the time of admission; preoperative intracranial pressure > 60 mmHg; cognitive impairment before the onset of the disease; hematologic disorders; or impaired functioning of the heart, liver, kidneys, or other visceral organs. Depending on the surgical approach, the patients were categorized into decompressive craniectomy group as well as basal cisternostomy group. General data and postoperative indicators, including Glasgow coma scale, intracranial pressure, etc., were recorded for both groups of patients. Among them, the Glasgow outcome scale extended assessment at 6 months served as the primary outcome. After that, the data were statistically analyzed using SPSS software. RESULTS: The trial enrolled 41 patients (32 men and 9 women) who met the inclusion criteria. Among them, 25 patients received decompressive decompressive craniectomy, and 16 patients received basal cisternostomy. Three days postoperative intracranial pressure levels were 10.07 ± 2.94 mmHg and 17.15 ± 14.65 mmHg (p = 0.013), respectively. The 6 months following discharge Glasgow outcome scale extended of patients was 4.73 ± 2.28 and 3.14 ± 2.15 (p = 0.027), respectively. CONCLUSION Our study reveals that basal cisternostomy in patients with surgically treated severe TBI has demonstrated significant efficacy in reducing intracranial pressure as well as patient prognosis follow-up and avoids removal of the bone flap. The efficacy of cisternostomy has to be studied in larger, multi-clinical center randomized trials.
Humans ; Brain Injuries, Traumatic/surgery* ; Retrospective Studies ; Male ; Female ; Adult ; Middle Aged ; Decompressive Craniectomy/methods* ; Aged ; Young Adult ; Adolescent ; Glasgow Coma Scale ; Treatment Outcome

Gene therapy, harnessing the power of CRISPR-Cas9 and/or DNAzyme systems, stands as a pivotal approach in cancer therapy, enabling the meticulous manipulation of genes pivotal to tumorigenesis and immunity. However, the pursuit of precise gene therapy encounters formidable hurdles. Herein, a near-infrared upconversion theranostic nanomachine is devised and tailors for CRISPR-Cas9/DNAzyme systems mediate precise gene therapy. An ingenious logic DNAzyme system consists of Chain 1 (C1)/Chain 2 (C2) and endogenous lncRNA is designed. We employ manganese modified upconversion nanoparticles for carrying ultraviolet-responsive C1-PC linker-C2 (C₂P) chain and Cas9 ribonucleoprotein (RNP), with outermost coats with hyaluronic acid. Upon reaching tumor microenvironment (TME), the released Mn²⁺ ions orchestrate a trifecta: facilitating endosomal escape, activating cGAS-STING signaling, and enabling T1-magnetic resonance imaging. Under near-infrared irradiation, Cas9 RNP/C₂P complex dissociates, releasing Cas9 RNP into the nucleus to perform gene editing of Ptpn2, while C1/C2 chains self-assemble with endogenous lncRNA to form a functional DNAzyme system, targeting PD-L1 mRNA for gene silencing. This strategy remodels the TME by activating cGAS-STING signaling and dual immune checkpoints blockade, thus realizing tumor elimination. Our theranostic nanomachine armed with the CRISPR-Cas9/DNAzyme logic systems, represents a resourceful and promising strategy for advancing cancer systemic immunotherapy and precise gene therapy.

[摘 要] 以CD19靶点为代表的嵌合抗原受体基因修饰T（CAR-T）细胞在B细胞恶性肿瘤治疗中取得突破性进展，但随着CAR-T细胞治疗患者数量的增加，复发、抵抗问题已成为临床亟待解决的问题和领域内研究热点。近年来除抗原丢失引发的免疫逃逸及CAR-T细胞失能导致的治疗不敏感外，对于肿瘤细胞自身内在因素异常等导致的治疗抵抗的研究也取得了一定的进展。基于高通量的筛选体系，促凋亡分子[如佛波醇-12-肉豆蔻酸-13-乙酸酯诱导蛋白-1（PMAIP1，又称NOXA）、Fas相关死亡域蛋白（FADD）等]和黏附分子[如CD58、细胞间黏附分子-1（ICAM-1）等]表达降低或缺失介导的抵抗机制相继被识别。对于目前已被识别的抵抗机制，已形成多种针对性的逆转策略，如组蛋白去乙酰化酶（HDAC）抑制剂联合CAR-T细胞治疗NOXA低表达的非霍奇金淋巴瘤；表观遗传学药物预处理CAR-T细胞增加其抗瘤效能与持久性；通过基因编辑技术解除相关基因的抑制作用从而增效CAR-T细胞；过表达细胞因子改善肿瘤微环境等，且部分策略已获得临床验证。本文综述已有CAR-T细胞治疗的抵抗机制及其针对性逆转策略，分析了相关研究的临床转归，旨在为提升CAR-T细胞在B细胞肿瘤中的疗效提供新的思路。

5-Hydroxytryptamine(5-HT)type 3 receptor(5-HT3R)is the only type of ligand-gated ion channel in the 5-HT receptor family.Through the high permeability of Na+,K+,and Ca2+ and activation of subsequent voltage-gated calcium channels(VGCCs),5-HT3R induces a rapid increase of neuronal excitability or the release of neurotransmitters from axon terminals in the central nervous system(CNS).5-HT3Rs are widely expressed in the medial prefrontal cortex(mPFC),amygdala(AMYG),hippocampus(HIP),periaqueductal gray(PAG),and other brain regions closely associated with anxiety reactions.They have a bidirectional regulatory effect on anxiety reactions by acting on different types of cells in different brain regions.5-HT3Rs mediate the activation of the cholecystokinin(CCK)system in the AMYG,and the γ-aminobutyric acid(GABA)"disinhibition"mechanism in the prelimbic area of the mPFC promotes anxiety by the activation of GABAergic intermediate inhibitory neurons(IINs).In contrast,a 5-HT3R-induced GABA"disinhibition"mechanism in the infralimbic area of the mPFC and the ventral HIP produces anxiolytic effects.5-HT2R-mediated regulation of anxiety reactions are also activated by 5-HT3R-activated 5-HT release in the HIP and PAG.This provides a theoretical basis for the treatment of anxiety disorders or the production of anxiolytic drugs by targeting 5-HT3Rs.However,given the circuit specific modulation of 5-HT3Rs on emotion,systemic use of 5-HT3R agonism or antagonism alone seems unlikely to remedy anxiety,which deeply hinders the current clinical application of 5-HT3R drugs.Therefore,the exploitation of circuit targeting methods or a combined drug strategy might be a useful developmental approach in the future.

Objective:To construct a prognostic predictive model for patients with moderate to severe traumatic brain injury (msTBI) based on regional cerebral oxygen saturation (rScO 2) and transcranial Doppler ultrasound (TCD) monitoring parameters and validate its effectiveness. Methods:A retrospective cohort study was conducted to analyze the clinical data of 161 patients with msTBI who were treated at Henan Provincial People′s Hospital from January 2021 to December 2022, including 104 males and 57 females, aged 19-76 years [(53.1±12.8)years]. Glasgow coma scale (GCS) score was 3-12 points [(7.0±1.9)points]. Both rScO 2 and TCD monitoring were performed. Based on the results of prognostic evaluation of patients with the modified Rankin scale (mRS) score at 90 days after discharge, the patients were divided into good prognosis group (mRS score≤3 points, n=88) and poor prognosis group (mRS score of 4-6 points, n=73). The following data of the two groups were collected: the general data, clinical data, rScO 2 monitoring parameters and TCD monitoring parameters. Univariate analysis was employed to compare the differences in the relevant prognostic indicators. Multivariate Logistic stepwise regression analysis was conducted to determine the predictors of poor prognostic outcomes in msTBI patients and regression equations were constructed. A nomogram predictive model based on regression equations was drawn with R language. The discriminability of the model was evaluated by drawing the receiver operating characteristic (ROC) curve, to calculate the area under the curve (AUC), sensitivity, specificity, and Jordan index of the model, and measuring the consistency index (C index). Hosmer-Lemeshow (H-L) goodness of fit test was conducted to evaluate the fit of the model, and the calibration curve was used to evaluate the calibration degree of the model. Decision curve analysis (DCA) was employed to evaluate the clinical benefit and applicability of the model. Results:There were significant differences between the two groups in the clinical data (cerebral hernia formation, GCS on admission, acute physiology and chronic health evaluation II (APACHE II) score on admission, Rotterdam CT score on admission, oxygenation index on admission, mean arterial pressure on admission), rScO 2 monitoring parameters (mean rScO 2, maximum rScO 2, rScO 2 variability), TCD monitoring parameters [peak systolic blood flow velocity (Vs), average blood flow velocity (Vm), pulse index (PI)] ( P<0.05 or 0.01). The results of multivariate Logistic stepwise regression analysis showed that cerebral hernia formation ( OR=9.28, 95% CI 3.40, 25.33, P<0.01), Rotterdam CT score on admission ( OR=1.92, 95% CI 1.32, 2.78, P<0.01), rScO 2 variability ( OR=4.66, 95% CI 1.74, 12.43, P<0.01), Vs ( OR=0.66, 95% CI 0.61, 0.75, P<0.01) and PI ( OR=20.07, 95% CI 4.17, 16.50, P<0.01) were predictive factors for poor prognosis in patients with msTBI. The regression equation was constructed with the forementioned 5 variables: Logit [ P/(1- P)]=2.23×"brain hernia formation"+0.65×"Rotterdam CT score on admission"+1.54×"rScO 2 variability"-0.42×"Vs"+3.00×"PI"-6.75. The AUC of prognostic predictive model of msTBI patients was 0.90 (95% CI 0.85, 0.95), with the sensitivity and specificity of 86.3% and 78.4%, Youden index of 0.65 and C index of 0.90. H-L goodness of fit test showed that the calibration degree of the predictive model was accurate ( χ2 =12.58, P>0.05). The average absolute error of the calibration curve was 0.025, showing that the calibration of the model was good. DCA results showed that this model had higher net return rate than the reference model within the probability range of risk threshold (20%-100%), with good clinical application value in evaluating the risk of poor prognosis of msTBI patients. Conclusion:The model constructed based on the combination of rScO 2 and TCD monitoring parameters (rScO 2 variability, Vs and PI) with multiple clinical indicators (cerebral hernia formation and Rotterdam CT score on admission) has good predictive performance for the prognosis of msTBI.

Patients with severe trauma require an extremely timely treatment and transfusion plays an irreplaceable role in the emergency treatment of such patients. An increasing number of evidence-based medicinal evidences and clinical practices suggest that patients with severe traumatic bleeding benefit from early transfusion of low-titer group O whole blood or hemostatic resuscitation with red blood cells, plasma and platelet of a balanced ratio. However, the current domestic mode of blood supply cannot fully meet the requirements of timely and effective blood transfusion for emergency treatment of patients with severe trauma in clinical practice. In order to solve the key problems in blood supply and blood transfusion strategies for emergency treatment of severe trauma, Branch of Clinical Transfusion Medicine of Chinese Medical Association, Group for Trauma Emergency Care and Multiple Injuries of Trauma Branch of Chinese Medical Association, Young Scholar Group of Disaster Medicine Branch of Chinese Medical Association organized domestic experts of blood transfusion medicine and trauma treatment to jointly formulate Chinese expert consensus on blood support mode and blood transfusion strategies for emergency treatment of severe trauma patients ( version 2024). Based on the evidence-based medical evidence and Delphi method of expert consultation and voting, 10 recommendations were put forward from two aspects of blood support mode and transfusion strategies, aiming to provide a reference for transfusion resuscitation in the emergency treatment of severe trauma and further improve the success rate of treatment of patients with severe trauma.

Objective:To understand the composition of respiratory virus spectrum in hospitalized children with acute respiratory infections in Guilin City from 2021 to 2022, and to explore the epidemic characteristics of different respiratory viruses.Methods:Information of a total of 638 hospitalized children with acute respiratory infections (ARI) syndrome under the age of 14 years in Guilin city, Guangxi from September 2021 to October 2022 was collected as research data. The collected pharyngeal swabs from pediatric patients were subjected to real-time fluorescence reverse transcription polymerase chain reaction for nucleic acid testing, screening for 15 common respiratory viruses, and analyzing the virus spectrum characteristics of hospitalized pediatric patients with acute respiratory infections.Results:Among the 638 specimens, 365 were tested positive for at least one virus, with a positive rate of 57.21% (365/638). The detection rate for two or more viruses was 12.85% (82/638). There were 12 types of viruses detected, and the difference in virus detection rates among different seasons was statistically significant (P<0.002). The virus positive detection rate of samples from different age groups was the highest in the 0-2-year old group (40.66%), followed by the 3-5-year old group (34.80%) and the 6-year and older group (24.54%).Conclusions:During the period from September 2021 to October 2022, all 12 respiratory viruses were prevalent in Guilin area, with obvious summer peak as characteristics. It is suggested that corresponding prevention and control measures should be focused on pathogens that may cause acute respiratory infections in children during the local summer to prevent and control the spread and prevalence of respiratory infections.

Objective:To understand the prevalence and characteristics of Rhinovirus (HRV) infection in influenza-like Illness (ILIs) patients in Mianyang, Sichuan province, China.Methods:Throat swabs were collected from patients of ILIs in sentinel hospitals in Mianyang during 2021—2022. Real-time fluorescence quantitative PCR was used to detect 16 common pathogens. The VP4/VP2 coding region genes of HRV positive samples were amplified by nest PCR. The phylogeny, consistency and amino acid variation of different serotypes were analyzed and compared with reference sequences from GenBank database.Results:A total of 332 ILIs′ samples were collected with a virus detection rate of 58.73% (195/332) in Mianyang. Among them, 23 samples (23/332) were HRV-positive, and 18 VP4/VP2 sequences of HRV strains were successfully amplified. It was found that 13 HRV serotypes were detected in ILIs samples in Mianyang, which belonged to three genotypes, namely HRV-A (12 strains), HRV-B (5 strains) and HRV-C (1 strain).Conclusions:HRV was one of the pathogens of ILIs cases in Mianyang during 2021—2022, with HRV-A types as the dominant strains.