Hypoxia-inducible factor (HIF-1α), a core transcription factor responding to changes in cellular oxygen levels, is closely associated with a wide range of physiological and pathological conditions. However, its differential impacts on vascular cell types and molecular programs modulating human vascular homeostasis and regeneration remain largely elusive. Here, we applied CRISPR/Cas9-mediated gene editing of human embryonic stem cells and directed differentiation to generate HIF-1α-deficient human vascular cells including vascular endothelial cells, vascular smooth muscle cells, and mesenchymal stem cells (MSCs), as a platform for discovering cell type-specific hypoxia-induced response mechanisms. Through comparative molecular profiling across cell types under normoxic and hypoxic conditions, we provide insight into the indispensable role of HIF-1α in the promotion of ischemic vascular regeneration. We found human MSCs to be the vascular cell type most susceptible to HIF-1α deficiency, and that transcriptional inactivation of ANKZF1, an effector of HIF-1α, impaired pro-angiogenic processes. Altogether, our findings deepen the understanding of HIF-1α in human angiogenesis and support further explorations of novel therapeutic strategies of vascular regeneration against ischemic damage.
Humans ; Vascular Endothelial Growth Factor A/metabolism* ; Endothelial Cells/metabolism* ; Transcription Factors/metabolism* ; Gene Expression Regulation ; Hypoxia/metabolism* ; Cell Hypoxia/physiology*

Objective To investigate the clinical features of rhino-orbital-cerebral mucormycosis(ROCM)with bilateral cranial nerve palsies as the clinical manifestation.Methods The related clinical data about ROCM with bilateral cranial nerve palsy as a clinical manifestation was collected,analyzed as well as discussed in the manuscript.And the relevant literatures were reviewed.Results This patient was a healthy young man with new-onset diabetes and diabetic ketoacidosis.The patient developed rapidly with acute onset,bilateral blindness,blepharoptosis and extraocular muscle paralysis.The presence of mucormycosis was confirmed by CSF second-generation sequencing,fungal fluorescent staining and culture.Although effective antifungal therapy was performed early,but the patient quickly presented with cerebral hemorrhage and herniation.Eventually,the patient died after discharge.Conclusions ROCM is a rare and high-mortality infectious disease.This case indicated that the clinicians should consider the presence of ROCM in patients with diabetes/diabetic ketoacidosis when the bilateral cranial nerves paralysis are the clinical symptom,whicn can not be explained by other lesions.CSF next-generation sequencing is helpful for rapid diagnosis.

Objective To study the effect of different types of renal puncture needles on the risk of bleeding after renal puncture.Methods A retrospective analysis was performed on 428 patients who under-went renal biopsy in the Third Affiliated Hospital of Chongqing Medical University and Jiulongpo District People's Hospital of Chongqing from January 2020 to December 2022.Different types of puncture needles were used to compare the occurrence of postoperative bleeding complications(hematoma,hematuria).Results The incidence of bleeding complications after renal puncture in 428 patients was 21.0％(90/428),of which the incidence of hematoma was 18.9％(81/428),the incidence of hematuria was 2.1％(9/428),the median decrease in hemoglobin(Hb)was 5 g/L,and the incidence of serious complications such as blood transfusion and interventional therapy was 0.7％(4/428).The patients with different types of renal puncture needles were grouped(16G group,18G group).There was no significant difference in baseline data and distri-bution of renal pathological types between the two groups(P＞0.05).The incidence of postoperative bleeding in 16G group and 18G group was 22.4％(52/232)and 19.4％(38/196),respectively.The incidence of hema-toma was 20.6％(48/232)and 16.8％(33/196),respectively.The incidence of hematuria was 1.7％(4/232)and 2.6％(5/196),respectively.The decrease of Hb was 6(0,16)g/L and 4(0,17)g/L,respectively.There was no significant difference(P＞0.05).There was no significant difference in the incidence of serious compli-cations such as blood transfusion,interventional therapy and Hb decrease＞10 g/L between the two groups(P＞0.05).Conclusion Ultrasound-guided renal biopsy is safe and has a low incidence of serious complica-tions.There was no significant relationship between different puncture needle types and postoperative bleeding risk.

Sepsis-associated encephalopathy (SAE) is the most common neurological complication of sepsis, with an incidence of up to 70% in sepsis, and contributes to the increased mortality and disability in sepsis. To date, the exact pathogenesis of SAE is not clear. Most of current researches indicated that blood-brain barrier (BBB) dysfunction, active neuroinflammation, glial cell over activation as well as cerebral microcirculation dysfunction contributed to the pathophysiology of SAE. BBB, as a complex cellular structure between the central nervous system and the peripheral system, strictly controls the entrance and discharge of substances and plays an important role in maintaining the balance between biochemical system and immune system of central system. During the progress of sepsis, inflammatory cytokines and reactive oxygen species resulting from peripheral system directly or indirectly resulted in the damage to the integrity and structure of BBB, which helped above species easily enter into the central system. Above these damages caused glial cell activation (microglia and astrocyte), the imbalance of neurotransmitters, mitochondrial dysfunction and neural apoptosis, which also reversely contributed to the damage to the integrity and permeability of BBB via decreasing the expression of tight junctional protein between cells. Therefore, this review focuses on the structural and functional changes of BBB in SAE, and how these changes lead to the development of SAE, in order to seek a BBB-targeted therapy for SAE.

Objective·To analyze the epidemiological characteristics of risk factors for cardiovascular diseases and malignant tumors based on the Shanghai community elderly cohort.Methods·The study subjects were selected from the Shanghai community elderly cohort established from February to August 2019,with a total of 17 948 people.The study subjects were divided into 4 groups according to self-reported presence or absence of tumors and/or cardiovascular diseases during the baseline survey:tumor-free and non-cardiovascular disease group,single cardiovascular disease group,single tumor group and tumor cardiovascular disease co-occurrence group.The differences among the four groups of subjects were collected and compared in terms of demographic characteristics and physiological indicators,daily living habits(smoking,drinking tea,drinking coffee,drinking carbonated drink,drinking alcohol,sedentary time,physical activity level and sleep quality),past medical history,psychological status(depression and anxiety)and dietary compliance.Results·Among the study subjects,60.1%of tumor patients were complicated with cardiovascular diseases.The differences among the four groups of subjects in age,gender,educational level,pre-retirement occupation,waist circumference,hip circumference and body mass index were statistically significant(all P<0.05).Compared with the tumor-free and non-cardiovascular disease group,the single cardiovascular disease group,single tumor group and tumor cardiovascular disease co-occurrence group all exhibited lower proportions of smoking and high physical activity levels(all P<0.05),and higher proportion of sedentary time exceeding 4 h/d and poor sleep quality(all P<0.05);the proportion of subjects with past medical histories including hyperlipidemia,peripheral vascular disease,endocrine system disease,respiratory system disease,urinary system disease and digestive system disease of the single cardiovascular disease group and the tumor cardiovascular disease co-occurrence group was higher(all P<0.05),and the proportion of subjects with depression and anxiety was also higher(all P<0.05).Furthermore,compared with the tumor-free and non-cardiovascular disease group,the single cardiovascular disease group had lower compliance rates of poultry,fish,fruit and liquid milk(all P<0.05).Among the four groups,only the compliance rate of vegetable intake exceeded 50%,while the compliance rates of poultry,fish,fruit,liquid milk and tubers were all below 20%.Conclusion·In the elderly population of Shanghai communities,over half of malignant tumor patients are concomitant with cardiovascular diseases.Unhealthy daily habits are prevalent among those with cardiovascular diseases,tumors and tumor-cardiovascular disease co-occurrence.The intake of many foods in the elderly of the community do not reach the levels recommended by Chinese Dietary Guidelines.

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 explore the otherness of orthotopic injection of cell suspensions and transplantation of tumor tissue blocks to establish orthotopic implantation models of hepatocellular carcinoma in mice,and to provide a technical reference for the establishment of an orthotopic implantation model.Methods Healthy KM mice were divided into four groups:group A,direct injection of H22 cells;group B,direct injection of H22 ascitic cells;group C,transplantation of tissues;and group D,direct injection of saline.Activity and weight changes were observed regularly in each group and survival times were recorded.Liver tumor formation,tumor size,abdominal organ adhesion degree,and metastasis were observed in all groups.B-ultrasound imaging was performed,concentrations of alpha fetoprotein(AFP)and abnormal prothrombin(DCP)were detected,and liver histopathological changes were detected by hematoxylin and eosin staining.Results Mice molding operation time in groups A,B,and C were(3.36±0.44)min,(3.30±0.41)min,and(5.68±0.65)min,respectively.After modeling for 25 days,the rates of model formation in groups A,B,and C were all 100.0%.Severe abdominal adhesions occurred in 40.0%of mice in group A and 60.0%in group B,but in no mice in group C or D.Ascites occurred in 40.0%,100.0%,and 0.0%and abdominal wall tumors in 30.0%,60.0%,and 0.0%of mice in groups A,B,and C,respectively,while 40.0%of mice in group B also had liver metastasis.B-ultrasound imaging,detection of serum AFP and DCP levels,and histopathological result showed smooth liver margins,uneven echo and slightly lower echo mass,maintained high AFP and DCP secretion,and large numbers of inflammatory cells and tumor cells in mice in groups A,B,and C.Conclusions At day 25,all three methods can thus be used to establish orthotopic transplantation models of HCC.Among these,inj ection of cell suspensions demonstrated the advantage of simplicity in operation and the presence of multiple metastatic nodules within the liver,compared to transplantation of tumor tissue.Conversely,transplantation of tumor tissue showed the advantage of causing less impact on the abdomen and other organs when compared to inj ection of cell suspensions.

OBJECTIVE To predict biomarkers of type 2 inflammation in chronic rhinosinusitis with nasal polyps(CRSwNP)by employing peripheral blood indicators.METHODS CRSwNP patients admitted to the Rhinology Department of Beijing Tongren Hospital from June 2020 to May 2022 were enrolled and their basic clinical data were collected.The blood percentage of eosinophils(Eos%),Eos count,periostin and total IgE,as well as mucosal interleukin-5(IL-5)and Staphylococcus aureus enterotoxin-immunoglobulin E(SE-IgE)were tested.The receiver operating characteristic(ROC)curve was used to evaluate the predictive value of each blood indicator for positive mucosal expression of IL-5/SE-IgE.The logistic regression was employed to screen multiple blood indicators with predictive value for positive mucosal expression of IL-5/SE-IgE in order to construct a nomogram model.RESULTS The proportion of asthma,blood Eos%,periostin and total IgE in CRSwNP patients showed statistical differences between IL-5/SE-IgE positive and negative subgroups.ROC univariate analysis demonstrated that blood Eos%,Eos count,periostin and total IgE could predict mucosal IL-5 positivity with AUC ranging from 0.655 to 0.784,and mucosal SE-IgE positivity with AUC ranging from 0.721-0.802.The logistic regression confirmed that blood Eos%and total IgE,as well as blood periostin and total IgE were independent predictors for mucosal IL-5 and SE-IgE positivity,respectively.The nomogram models were constructed for predicting IL-5/SE-IgE positivity in CRSwNP mucosa,with consistency incides(C-index)of 0.804 and 0.81,indicating good predictive accuracy.CONCLUSION The nomograms constructed based on blood Eos%and total IgE,as well as blood periostin and total IgE,could have good predictive value for the positive mucosal expression of IL-5 and SE-IgE in the CRSwNP,which help to predict the severity of endotype and phenotype of CRSwNP.

Objective To investigate the impact of esketamine hydrochloride in combination with ultrasound-guided transverse thoracic muscle plane block on stress response and inflammatory levels in patients undergoing cardiac valve replacement under general anesthesia.Methods A total of 120 patients who underwent elective extra-corporeal circulation-supported median open heart valve replacement were selected and randomly assigned into four groups using the random number table method:general anesthesia alone(Group G),general anesthesia with intrave-nous administration of esketamine(Group E),general anesthesia with transverse thoracic plane block(Group T),and esketamine combined with transverse thoracic muscle plane block(Group ET);each group consisted of 30 cases.Patients in group E and group ET received a continuous infusion of esketamine hydrochloride injection at a rate of 0.2 mg/kg-1?h-1 until the completion of the surgical procedure,while patients in group G and group T received an equivalent volume of saline solution until the completion of the surgical procedure.After the induction of general anesthesia,patients in group T and group ET underwent ultrasound-guided bilateral transverse thoracic muscle plane block,while patients in group G and group E did not receive any specific intervention.All four groups received identical protocols for anesthesia induction and maintenance,with self-controlled intravenous analgesic pumps administered to all patients postoperatively.The following time points were recorded:1 day prior to surgery(T0),pre-induction of anesthesia(T1),1 minute post-tracheal intubation(T2),1 minute post-median sternotomy(T3),1 minute prior to initiation of cardiopulmonary circulation(T4),1 minute after cessation of cardiopulmonary circula-tion(T5),1 minute after completion of surgery(T6),1 day post-surgery(T7),2 days post-surgery(T8),and 3 days post-surgery(T9).Mean Arterial Pressure(MAP)and Heart Rate(HR)were continuously monitored from T1 to T6.The levels of blood glucose and lactate were measured and recorded at T1,T4 to T6.The levels of White Blood Cells(WBC)and C-Reactive Protein(CRP)were assessed at T0,as well as at T7 to T9.The occurrence of postoperative adverse reactions was documented in all four groups.Results(1)Comparison of hemodynamics among the four groups:Compared with group G,there was a significant decrease in MAP and HR at T3 in group T(P<0.05).At the T5 time point,MAP was lower in group ET compared to group E,while HR was higher in group ET compared to group T(P<0.05).(2)The lactate and blood glucose levels of the four patient groups after extracorporeal circulation transfer were higher than those at the T1 time point(P<0.05).Patients in group E had lower lactate values at the T5 time point and lower blood glucose values at the T6 time point compared to group G(P<0.05).Additionally,patients in group E exhibited lower lactate and blood glucose values at both the T5 and T6 time points compared to those in group T(P<0.05).(3)Compared to T0,the levels of white blood cells(WBC)and C-reactive protein(CRP)were increased in all four groups after surgery(P<0.05).At the T7 time point,the WBC levels in group E and group T were significantly lower than those in group G(P<0.05).Furthermore,compared to group E and group T,the level of WBC in group ET was significantly lower at T7,while the level of CRP was significantly lower at T8(P<0.05).(4)There were no significant differences observed in postoperative adverse reactions among the four groups(P>0.05).Conclusion Combining low-dose esketamine hydrochloride with transverse thoracic muscle plane block under general anesthesia during open heart valve replacement surgery can effectively stabilize the patient's hemodynamics,mitigate perioperative stress response and postoperative inflammation levels,thereby demonstrating significant clini-cal utility.

Objective:To construct a novel dual-specific antibody targeting human CD123 (CD123 DuAb) and study its effects in acute myeloid leukemia (AML) .Methods:Based on the variable region of the CD123 monoclonal antibody independently developed at our institution, the CD123 DuAb expression plasmid was constructed by molecular cloning and transfected into ExpiCHO-S cells to prepare the antibody protein. Through a series of in vitro experiments, its activation and proliferation effect on T cells, as well as the effect of promoting T-cell killing of AML cells, were verified.Results:① A novel CD123 DuAb plasmid targeting CD123 was successfully constructed and expressed in the Expi-CHO eukaryotic system. ②The CD123 DuAb could bind both CD3 on T cells and CD123 on CD123 + tumor cells. ③When T cells were co-cultured with MV4-11 cells with addition of the CD123 DuAb at a concentration of 1 nmol/L, the positive expression rates of CD69 and CD25 on T cells were 68.0% and 44.3%, respectively, which were significantly higher than those of the control group ( P<0.05). ④Co-culture with CD123 DuAb at 1 nmol/L promoted T-cell proliferation, and the absolute T-cell count increased from 5×10 5/ml to 3.2×10 6/ml on day 9, and CFSE fluorescence intensity decreased significantly. ⑤ With the increase in CD123 DuAb concentration in the culture system, T-cell exhaustion and apoptosis increased. When the CD123 DuAb was added at a concentration of 1 nmol/L to the culture system, the proportion of CD8 + PD-1 + LAG-3 + T cells was 10.90%, and the proportion of propidium iodide (PI) - Annexin Ⅴ + T cells and PI + Annexin Ⅴ + T cells was 18.27% and 11.43%, respectively, which were significantly higher than those in the control group ( P<0.05). ⑥ The CD123 DuAb significantly activated T cells, and the activation intensity was positively correlated with its concentration. The expression rate of CD107a on T cells reached 16.05% with 1 nmol/L CD123 DuAb, which was significantly higher than that of the control group ( P<0.05). ⑦The CD123 DuAb promoted cytokine secretion by T cells at a concentration of 1 nmol/L, and the concentration of IFN-γ and TNF-α in the supernatant of the co-culture system reached 193.8 pg/ml and 169.8 pg/ml, respectively, which was significantly higher than that of the control group ( P<0.05). ⑧When CD123 DuAb was added at a concentration of 1 nmol/L to the co-culture system of T cells and CD123 + tumor cells, the killing intensity of T cells significantly increased, and the residual rates of CD123 + MV4-11 cells, CD123 + Molm13 cells, and CD123 + THP-1 cells were 7.4%, 6.7%, and 14.6% on day 3, respectively, which were significantly lower than those in the control group ( P<0.05) . Conclusion:In this study, a novel CD123 DuAb was constructed and expressed. In vitro experiments verified that the DuAb binds to CD123 + tumor cells and T cells simultaneously, promotes T-cell activation and proliferation, and facilitates their anti-leukemia effect, which provides a basis for further clinical research.