Objective To analyze the efficacy and adverse reactions of donepezil in the treatment of patients with a continuous disease spectrum of Alzheimer's disease(AD)with pharmacogenomics.Methods Seventy-two patients who took donepezil therapy at the time of initial molecular pa-thology diagnosis of AD continuous disease spectrum in Chinese PLA General Hospital from Jan-uary 2022 to January 2023 were recruited.Cells from the oral buccal mucosa were collected,and MassARRAY nucleic acid mass spectrometry was applied to detect the genotypes of CYP2D6,the gene encoding cytochrome P450 2D6 enzyme,and CHAT,the gene encoding acetylcholine trans-ferase.After 9 months of follow-up,drug efficacy was indirectly determined by neurological func-tion scales,caregiver evaluations,and drug prescribing behaviors,and thus,the 50 patients on donepezil alone were divide into effective group(n=28)and ineffective group(n=22).Seventy-two patients were divided into adverse reaction group(n=12)and no adverse reaction group(n=60).Multivariate logistic regression analysis was used to analyze the correlation between donepezil efficacy and pharmacogenomics.Results The frequencies of CHAT rs3793790 locus carrying G allele and rs2177370 locus carrying A allele were significantly higher in the effective group than the ineffective group(35.71％vs 9.09％,P=0.029;42.86％vs 9.09％,P=0.008).Multivariate lo-gistic regression analysis showed that donepezil was more effective in those who carrying rs3793790 G allele and/or rs2177370 A allele in the CHAT gene than those who carrying neither of the alleles(95％CI:1.20-34.47,P=0.030).There were no statistical differences in the CYP2D6 gene-adjusted activity score and whether or not carrying*10 between the patients with and without adverse reactions(P＞0.0 5).Conclusion In patients with a continuous spectrum of AD,donepezil efficacy is associated with CHAT gene polymorphisms,but there is no correlation between donepezil adverse reactions and CYP2D6 genotype.

Objective:To explore potential predictors of refractory Mycoplasma pneumoniae pneumonia (RMPP) in early stage. Methods:The prospective multicenter study was conducted in Zhejiang, China from May 1 st, 2019 to January 31 st, 2020. A total of 1 428 patients with fever >48 hours to <120 hours were studied. Their clinical data and oral pharyngeal swab samples were collected; Mycoplasma pneumoniae DNA in pharyngeal swab specimens was detected. Patients with positive Mycoplasma pneumoniae DNA results underwent a series of tests, including chest X-ray, complete blood count, C-reactive protein, lactate dehydrogenase (LDH), and procalcitonin. According to the occurrence of RMPP, the patients were divided into two groups, RMPP group and general Mycoplasma pneumoniae pneumonia (GMPP) group. Measurement data between the 2 groups were compared using Mann-Whitney U test. Logistic regression analyses were used to examine the associations between clinical data and RMPP. Receiver operating characteristic (ROC) curves were used to analyse the power of the markers for predicting RMPP. Results:A total of 1 428 patients finished the study, with 801 boys and 627 girls, aged 4.3 (2.7, 6.3) years. Mycoplasma pneumoniae DNA was positive in 534 cases (37.4%), of whom 446 cases (83.5%) were diagnosed with Mycoplasma pneumoniae pneumonia, including 251 boys and 195 girls, aged 5.2 (3.3, 6.9) years. Macrolides-resistant variation was positive in 410 cases (91.9%). Fifty-five cases were with RMPP, 391 cases with GMPP. The peak body temperature before the first visit and LDH levels in RMPP patients were higher than that in GMPP patients (39.6 (39.1, 40.0) vs. 39.2 (38.9, 39.7) ℃, 333 (279, 392) vs. 311 (259, 359) U/L, both P<0.05). Logistic regression showed the prediction probability π=exp (-29.7+0.667×Peak body temperature (℃)+0.004×LDH (U/L))/(1+exp (-29.7+0.667×Peak body temperature (℃)+0.004 × LDH (U/L))), the cut-off value to predict RMPP was 0.12, with a consensus of probability forecast of 0.89, sensitivity of 0.89, and specificity of 0.67; and the area under ROC curve was 0.682 (95% CI 0.593-0.771, P<0.01). Conclusion:In MPP patients with fever over 48 to <120 hours, a prediction probability π of RMPP can be calculated based on the peak body temperature and LDH level before the first visit, which can facilitate early identification of RMPP.

Objective:To study the localization value of stereoelectroencephalography (SEEG) in refractory epilepsy associated with tuberous sclerosis complex (TSC), and to analyze the prognosis related factors.Methods:A case control study.Data of 66 patients with TSC-related refractory epilepsy who underwent SEEG placement at the Epilepsy Center of Tsinghua University Yu-Quan Hospital from January 2014 to March 2023 were retrospectively analyzed, including medical history, seizure semiology, scalp electroencephalogram (EEG), imaging, and SEEG findings.Patients were divided into a seizure-free group and a seizure group according to the seizures after surgery. t/ χ2 test was used to compare the relationship between age of onset, age of surgery, duration of epilepsy, genetic findings, seizure symptoms, scalp EEG characteristics, SEEG placement protocol and prognosis. Results:A total of 66 patients met the enrollment criteria, of whom 55 patients were seizure-free after surgery (seizure-free group), and 11 patients still had seizures (seizure group).Among the 66 patients, there were 46 males and 20 females; the age of onset was (21.72±30.01) months; the age of SEEG surgery was (6.79±5.12) years; the duration of epilepsy was (4.98±4.11) years.SEEG results showed that seizures started with a single tuber in 43 patients (64.4%), seizures started with 2 or more tubers in one hemisphere in 16 patients, and 7 patients had bilateral multi-tubers or the pathogenic tuber(s) could not be identified.The following factors were found to be associated with prognosis: early age of surgery ( t=-3.463, P<0.01), ictal scalp EEG with a definite lateralization ( χ2=7.876, P<0.05), and the concordance of interictal and ictal EEG ( χ2=6.821, P<0.05).The age of onset, duration of epilepsy, seizure type and symptom, genetic findings, and SEEG placement protocol were not significantly correlated with prognosis.The results of SEEG identified that onset with a single tuber revealed a better postoperative outcome. Conclusions:This study confirms the safety and efficacy of SEEG in TSC-related refractory epilepsy, and also finds that ictal EEG is uniquely valuable in guiding SEEG placement for TSC-related refractory epilepsy, which can help us better select patients with TSC-related refractory epilepsy who are suitable for SEEG placement.

Objective To observe the effect of intraoperative continuous pump infusion of remima-zolam on postoperative delirium(POD)in elderly patients with hip fracture under subarachnoid block.Methods A total of 236 elderly patients undergoing elective hip fracture surgery under subarachnoid block,82 males and 154 females,aged≥65 years,BMI 18.5-31.0 kg/m2,ASA physical status Ⅰ-Ⅲ,were divided into two groups by using the randomized number table method:remimazolam group(group R)and control group(group C),118 patients in each group.When the surgical site was disinfected and cov-ered,the patients in group R were administered the first dose of reminmazolam 0.1 mg/kg and followed by a continuous infusion 0.2 mg·kg-1·h-1 intravenously to maintain the modified observer's assessment of alert/sedation(MOAA/S)1 or 2 scores.Reminmazolam infusion was stopped at the end of the surgery.The same volume of normal saline was injected for patients in group C.POD was assessed by the confusion as-sessment method-Chinese revised version(CAM-CR)1-3 days after the surgery.The anxiety scores one day before and one day after the surgery,and plasma cortisol concentrations when the patients were admitted into the operating room and at the end of the surgery were recorded.The incidence of intraoperative hypertension,hypotension,bradycardia,hypoxemia,and postoperative nausea and vomiting were also recor-ded.Results Compared with group C,POD incidence in group R was significantly decreased(P＜0.05),anxiety score one day after surgery and plasma cortisol concentration at the end of the surgery in group R were significantly decreased(P＜0.05),and the incidence of intraoperative hypertension in group R was significantly decreased(P＜0.05).There were no significant differences in the plasma cortisol con-centrations when the patients were admitted into the operating room and the incidences of intraoperative hy-potension,bradycardia,hypoxemia,and postoperative nausea and vomiting between the two groups.Conclusion Remimazolam can reduce the incidence of postoperative delirium in elderlypatients undergoing hip fracture surgery under subarachnoid block,which may be related to alleviating intraoperative anxiety and inhibiting intraoperative stress response.

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.

Background and purpose:In 2016 the National Cancer Institute(NCI)decided stopping to use NCI-60 cell lines for drug screening,suggesting that tumor cell lines were losing their value as a tool for drug discovery and basic research.The reason for NCI-60 cells'retirement'was that the preclinical studies based on traditional cellular and animal models did not obtain the corresponding expected efficacy in clinical trials.Since the major cancer behaviors,such as proliferation and metastasis,are fundamentally altered with long-term culture,the tumor cell lines are not representative of the characteristics of cancer in patients.Currently,scientists hope to create a new cancer model that are derived from fresh patient samples and tagged with details about their clinical past.Our purpose was to create patient-derived breast cancer primary cell lines as new cancer model for drug screening and basic research.Methods:Breast cancer tissues were collected in the Department of Breast Surgery,Affiliated Hospital of Guizhou Medical University.The collection of tumor tissue samples was approved by the Ethics Committee of the Affiliated Hospital of Guizhou Medical University(approval number:2022 ethics No.313),and the collection and use of tumor tissues complied with the Declaration of Helsinki.The primary breast cancer cell lines were isolated from the patient's breast cancer tissues and cultured in BCMI medium.After the cells proliferated,the media were replaced with DEME medium.Cell line STR genotyping was done to determine cell-specific genetic markers and identification.Clone formation assay and transplantation assay were done to analyze the ability of breast cancer primary cell lines to form tumors.Results:We created 6 primary breast cancer cell lines.The 6 primary breast cancer cell lines from the patients were tagged with the definitively clinicopathological features,clinical diagnosis,therapeutic regimens,clinical effectiveness and prognostic outcomes.The STR genotyping assays identified the genetic markers and determined the identities of the 6 primary breast cancer cell lines.Clone formation assays and transplantation assay showed that the proliferative capacities of the patient-derived primary breast cancer cell lines were significantly greater compared with the conventional breast cancer cell lines.Conclusion:We created a panel of 6 patient-derived primary breast cancer cell lines as new cancer model for drug screening and basic research in breast cancer.

Objective To analyze the current status,research hotspots and development trends in the field of immune responses in the microenvironment after spinal cord injury(SCI). Methods Literatrues about immune responses in the microenvironment after SCI were searched from CNKI and the Web of Science Core Collection,from inception to March,2024.VOSviewer and CiteSpace were used to conduct a vi-sual analysis of authors,countries,institutions,journals,co-cited references and keywords. Results A total of 152 Chinese and 455 English studies were included.The number of publications increased annually,and China and the United States were leading research efforts in this field.In the Chinese literature,Zhu Yue was the most prolific author,and China Medical University was the leading institution.In the English literature,Phil-lip Popovich was the most prolific and highly cited author,and Ohio State University was the leading institution.Journal of Neuroscience and Experimental Neurology were identified as key journals.The research hotspots in both languages focused on immune activation,inflammatory response and functional recovery.Researches on stem cell transplantation,macrophage and traditional Chinese medicine were particularly prominent in the regu-lation of immune responses after SCI. Conclusion Immune responses in the microenvironment have emerged as a central focus in SCI research.The emphasis of current researches is shifting from mechanistic exploration to the investigation of immunomodulatory strate-gies,with several cutting-edge technologies showing significant potential in this regard.Moving forward,increas-ing collaboration across regions and institutions are essential to promote information sharing,accelerate scientific progress,and facilitate clinical translation,ultimately enhance patient rehabilitation outcomes.

Objective To explore the regulatory role of hederagenin(HG)on glutamate(Glu)-in-duced ferroptosis and corresponding inflammatory responses in mouse hippocampal neuron HT22 cells and investigate its potential mechanisms.Methods HT22 cells were randomly divided into control,Glu and HG groups(n=3).The cells of the control group received no treatment,the cells of the Glu group were treated with 35 mmol/L Glu for 24 h to establish a cellular model of ferroptosis in Alzheimer's disease,and the cells of the HG group were treated with 0.5 μmol/L HG and 35 mmol/L Glu for 24 h simultaneously.FerroOrange fluorescent probe was used to de-tect intracellular Fe2+.The production of reactive oxygen species(ROS),mitochondrial membrane potential,and levels of inflammatory factors TNF-α,IL-1β and IL-6 in the cells were assessed.Finally,the expression of the key regulator of iron death,glutathione peroxidase 4(GPX4)was measured.Results Compared to the control group,the levels of intracellular Fe2+,ROS,TNF-α,IL-1β,and IL-6 were significantly elevated,while the mitochondrial membrane potential was obvi-ously reduced in the Glu group(P＜0.05,P＜0.01).The HG group had significantly decreased Fe2+,ROS,TNF-α,IL-1β,and IL-6 and enhanced mitochondrial membrane potential than the Glu group(P＜0.05,P＜0.01).The GPX4 expression was significantly lower in the Glu group than the control group(1.00±0.02 vs 0.46±0.04,P＜0.01),and was notably higher in the 0.5 and 1.0 μmol/L HG groups when compared to the Glu group(0.64±0.03 and 0.59±0.05 vs 0.46±0.04,P＜0.01).Conclusion HG inhibits ferroptosis by regulating GPX4 expression,and thereby effec-tively alleviates the inflammatory response.

Objective:To determine the risk factors for permanent nerve damage (PND) after aortic arch surgery in patients with acute type A aortic dissection (AAAD).Methods:This was a retrospective case-control study. The medical records from patients of both sexes with AAAD, aged > 18 yr, of American Society of Anesthesiologists Physical Status classification IV, who underwent aortic arch surgery in the Second Hospital of Hebei Medical University from December 2018 to December 2023, were collected. The patients were divided into non-PND group and PND group according to whether PND occurred after operation. The preoperative data of patients were collected, including age, gender, body mass index; comorbidities (hypertension, coronary heart disease, diabetes mellitus), history of smoking, history of stroke, and history of cardiovascular surgeries; syncope at onset, preoperative low SpO 2, preoperative low systolic blood pressure, and preoperative low diastolic blood pressure. The intraoperative data included surgical procedure (total aortic arch replacement or half aortic arch replacement), selective antegrade cerebral perfusion during operation, cardiopulmonary bypass (CPB) time, aortic cross-clamp time, post-parallel time, moderate hypothermia circulatory arrest time, nasopharyngeal temperature and rectal temperature during circulatory arrest, and BIS value during circulatory arrest; blood pressure during cardiopulmonary bypass and after restoration of heart beat; the incidence of dysfunction after recovery of heart beat and difficulty in hemostasis after termination of CPB. The aforementioned indicators were analyzed for difference, and the indicators with P<0.05 were included in the multivariate logistic regression analysis. Results:A total of 292 patients were ultimately included, among which 73 developed postoperative PND, resulting in an incidence of 25.0%. The results of multivariate logistic regression analysis showed that age ≥62 yr ( OR=3.783, 95% confidence interval [ CI] 1.513-10.346, P=0.006), preoperative hypertension ( OR=2.230, 95% CI 1.118-4.715, P=0.028), syncope at onset ( OR=3.001, 95% CI 1.343-6.710, P=0.007), BIS value > 14 during circulatory arrest ( OR=2.439, 95% CI 1.249-4.755, P=0.009) and difficult hemostasis after termination of CPB ( OR=3.465, 95% CI 1.758-6.882, P<0.001) were risk factors for PND after surgery. Conclusions:Age ≥ 62 yr, history of hypertension, syncope at onset, BIS value greater than 14 during circulatory arrest and difficulty in hemostasis after termination of CPB are risk factors for PND after aortic arch surgery in patients with AAAD.

Sepsis is a life-threatening organ dysfunction caused by infection that lead to dysregulation of the host response. Sepsis and septic shock with a high mortality threaten human health at present, which are important medical and health problems. Early diagnosis and treatment decision-making for sepsis and septic shock still need to be improved. Exosomes are extracellular vesicles with a diameter of 30-150 nm formed by the fusion of multi-vesicle bodies and cell membranes. Exosomes can effectively transport a variety of bioactive substances such as proteins, lipids, RNA, DNA, and participate in the regulation of inflammatory response, immune response, infection and other pathophysiological processes. In recent years, exosomes have become one of the important methods for the diagnosis and treatment of systemic inflammatory diseases. This article will focus on the basic and clinical research of sepsis, and focus on the research progress of exosomes in the diagnosis and targeted therapy of sepsis.
Humans ; Shock, Septic/therapy* ; Exosomes/metabolism* ; Sepsis/therapy* ; Extracellular Vesicles/metabolism* ; RNA/metabolism*