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*

Background and purpose:Trastuzumab has a relatively low incidence of drug resistance,which can be used as an adjuvant treatment to improve clinical efficacy.It has been used to treat breast cancer in the past,but its application in other cancers has been less studied.This study aimed to explore the effects of trastuzumab assisted modified DOF fortnightly regimen on serum tumor markers and survival rate in cisplatin-resistant gastric cancer patients,in order to provide more references for the selection of clinical treatment methods for cisplatin-resistant gastric cancer.Methods:Eighty patients with cisplatin-resistant gastric cancer treated in Harison International Peace Hospital from January 2017 to January 2019 were selected as the study objects,and they were divided into observation group and control group according to random number table method.All of them received improved DOF fortnightly treatment,and trastuzumab adjuvant treatment was added to the observation group on this basis.The serum tumor markers[serum carcinoembryonic antigen(CEA),carbohydrate antigen 19-9(CA19-9),CA72-4],serum neovascular markers[vascular endothelial growth factor(VEGF),pigment epithelial derived factor(PEDF),angiopoietin-2(Ang-2)],biochemical indicators[N-terminal pro B type natriuretic peptide(NT proBNP),aspartate transaminase(AST),blood urea nitrogen(BUN),alanine aminotransferase(ALT)],adverse reactions and survival rate were compared between two groups.This study was approved by the Ethics Committee of Harison International Peace Hospital(number:20160511).Results:After treatment,CEA,CA19-9 and CA72-4 in both groups decreased,and CEA,CA19-9 and CA72-4 levels were lower in the observation group than in the control group with statistical significance(P＜0.01).After treatment,VEGF,PEDF and Ang-2 in two groups decreased,and the difference was statistically significant(P＜0.01).The levels of VEGF,PEDF and Ang-2 were compared between the two groups before and after treatment,and there was no significant difference(P＞0.05).The levels of NT-proBNP,AST,BUN and ALT were compared between the two groups before and after treatment,and there was no statistically significant difference(P＞0.05).The number of patients with fatigue,gastrointestinal reaction and myelosuppression and the total incidence of adverse reactions were compared between the two groups,and there was no statistically significant difference(P＞0.05).At 5 years after treatment,11 cases(27.5%)survived and 29 cases(72.5%)died in the observation group.There were 3 cases(7.5%)of survival and 37 cases(92.5%)of death in the control group.The median survival was 2 years(95%CI:1.8-2.2)in the observation group and 1 year(95%CI:0.6-1.4)in the control group.The survival rate of 1-5 years was higher in the observation group than in the control group.The difference was statistically significant(log-rank χ2 = 13.853,P = 0.001).Conclusion:In the clinical treatment of cisplatin-resistant gastric cancer,trastuzumab assisted modified DOF fortnightly regimen suggests that it can reduce the expression levels of serum tumor markers,improve the 5-year survival rate of patients,and has certain drug safety.

OBJECTIVE To investigate the correlation between gene polymorphisms and adverse drug reaction （ADR） and demands of opioids， aiming to guide personalized opioid analgesic therapy. METHODS The existing evidence-based medical data were adopted to identify gene loci related to the efficacy and ADR of opioid analgesics and select highly relevant single nucleotide polymorphism （SNP） for a clinical case-control study. The study cohort was divided into two evaluation groups： ADR assessment and drug demand assessment. The ADR assessment group included 254 cancer pain patients and was subdivided into the trial subgroup （with ADR） and the control subgroup （without ADR） based on the presence or absence of ADR following opioid usage； the two subgroups included 126 and 128 patients， respectively. The drug demand assessment group included a total of 120 cancer pain patients， who were divided into trial subgroup （equivalent to a daily dose of oral morphine ≥100 mg） and control subgroup （equivalent to a daily dose of oral morphine ＜100 mg） based on the different daily doses of opioid analgesics， with 60 patients in each subgroup. Polymorphism detection of SNP loci in these patients was performed using fluorescence in situ hybridization. SPSS 21.0 software and SNPStats genetic models were employed to compare genetic testing results between subgroups and conduct correlation analyses， aiming to evaluate the association of the selected SNP loci with opioid ADR and drug demand inclinical real-world cases. RESULTS The strongly correlated SNP loci identified were CYP2D6*10（rs1065852，C＞T）， CYP3A5*3（rs776746，A＞G），ABCB1（rs1045642，C＞T）and OPRM1（rs1799971，A＞G）. Genetic testing results indicated that the allele frequency distributions of these SNP loci conformed to Hardy-Weinberg equilibrium. Correlation analysis revealed that in the ADR assessment group， compared with control subgroup， the proportion of patients in trial subgroup with the AA genotype of OPRM1 （rs1799971， A＞G） was significantly higher （P＜0.05）； in the drug demand assessment group， compared with control subgroup， the proportion of patients in trial subgroup with the CC+CT genotype of ABCB1 （rs1045642， C＞T） was significantly higher （P＜0.05）. CONCLUSIONS The AA genotype of OPRM1 （rs1799971， A＞G） is associated with the occurrence of ADR following oxycodone use. Patients with the CC+ CT genotype of ABCB1（ rs1045642， C＞T） require higher doses of opioid analgesics.

The COVID-19 epidemic has spread to the whole world for three years and has had a serious impact on human life, health and economic activities. China's epidemic prevention and control has gone through the following stages: emergency unconventional stage, emergency normalization stage, and the transitional stage from the emergency normalization to the "Category B infectious disease treated as Category B" normalization, and achieved a major and decisive victory. The designated hospitals for prevention and control of COVID-19 epidemic in Tianjin has successfully completed its tasks in all stages of epidemic prevention and control, and has accumulated valuable experience. This article summarizes the experience of constructing a hospital infection prevention and control system during the "Category B infectious disease treated as Category A" period in designated hospital. The experience is summarized as the "Cluster" hospital infection prevention and control system, namely "three rings" outside, middle and inside, "three districts" of green, orange and red, "three things" before, during and after the event, "two-day pre-purification" and "two-director system", and "one zone" management. In emergency situations, we adopt a simplified version of the cluster hospital infection prevention and control system. In emergency situations, a simplified version of the "Cluster" hospital infection prevention and control system can be adopted. This system has the following characteristics: firstly, the system emphasizes the characteristics of "cluster" and the overall management of key measures to avoid any shortcomings. The second, it emphasizes the transformation of infection control concepts to maximize the safety of medical services through infection control. The third, it emphasizes the optimization of the process. The prevention and control measures should be comprehensive and focused, while also preventing excessive use. The measures emphasize the use of the least resources to achieve the best infection control effect. The fourth, it emphasizes the quality control work of infection control, pays attention to the importance of the process, and advocates the concept of "system slimming, process fattening". Fifthly, it emphasizes that the future development depends on artificial intelligence, in order to improve the quality and efficiency of prevention and control to the greatest extent. Sixth, hospitals need to strengthen continuous training and retraining. We utilize diverse training methods, including artificial intelligence, to ensure that infection control policies and procedures are simple. We have established an evaluation and feedback mechanism to ensure that medical personnel are in an emergency state at all times.

Temporomandibular joint (TMJ) diseases are common clinical conditions. The number of patients with TMJ diseases is large, and the etiology, epidemiology, disease spectrum, and treatment of the disease remain controversial and unknown. To understand and master the current situation of the occurrence, development and prevention of TMJ diseases, as well as to identify the patterns in etiology, incidence, drug sensitivity, and prognosis is crucial for alleviating patients′suffering.This will facilitate in-depth medical research, effective disease prevention measures, and the formulation of corresponding health policies. Cohort construction and research has an irreplaceable role in precise disease prevention and significant improvement in diagnosis and treatment levels. Large-scale cohort studies are needed to explore the relationship between potential risk factors and outcomes of TMJ diseases, and to observe disease prognoses through long-term follw-ups. The consensus aims to establish a standard conceptual frame work for a cohort study on patients with TMJ disease while providing ideas for cohort data standards to this condition. TMJ disease cohort data consists of both common data standards applicable to all specific disease cohorts as well as disease-specific data standards. Common data were available for each specific disease cohort. By integrating different cohort research resources, standard problems or study variables can be unified. Long-term follow-up can be performed using consistent definitions and criteria across different projects for better core data collection. It is hoped that this consensus will be facilitate the development cohort studies of TMJ diseases.

A rapid quantitative immunochromatographic assay for procalcitonin(PCT)using metal-organic frameworks modified with gold and platinum nanoparticles(MAPs)as labels was established in this work.The detection probe was prepared by conjugating MAPs with anti-PCT monoclonal antibody via an electrostatic adsorption method.Anti-PCT polyclonal antibody and sheep anti-mouse IgG were sprayed onto the nitrocellulose(NC)membrane as the test line and quality control line,respectively,to construct immunochromatographic strip for PCT quantitative detection via signal-amplification-based sandwich immunoassay.The results showed that the MAP-based immunochromatographic test had high sensitivity,high specificity,and good stability.The dynamic range for detection of PCT was 0.61 pg/mL-320 ng/mL,the detection limit was 0.25 pg/mL,and the intra-day and inter-day precision(Relative standard deviation)were less than 15%.The results of real sample analysis showed that a quite low volume of sample was required for detection of PCT in whole blood,which was of great significance for the early diagnosis,monitoring and treatment,and prognosis of inflammation.

To explore the prevalence and related risk factors of osteoporosis (OP) in the elderly ≥60 years old in Jiuting Town, Songjiang District, Shanghai City. A total of 2 175 local residents aged ≥60 years old who participated in the questionnaire survey at the physical examination center of Jiuting Community Health Service Center, Songjiang District, Shanghai City from July 2021 to December 2022 were selected by a cross-sectional study with multi-stage sampling method. Questionnaire survey, blood test and bone mineral density (BMD) test were conducted.The differences in all the parameters among the elderly with different bone mass level were analyzed using t-test, chi-square test, binary logistic regression was used to screen the potential risk factors of OP.The results showed that the prevalence of OP in the elderly aged≥60 years old in Jiuting Town was 45.89%.The prevalence of OP increased gradually with the advanced age. The prevalence rate of male was significantly lower than that of female( χ2=211.94, P<0.01).Single factor analysis showed that Dairy products( χ2=9.01, P<0.05), taking calcium( χ2=42.88, P<0.05), physical exercise( χ2=24.73, P<0.05), exercise time( χ2=76.40, P<0.05) and sun exposure( χ2=55.71, P<0.05) were the protective factors for osteoporosis. Multifactor analysis showed that female( wald χ 2=71.46, P<0.001) were the risk factors for osteoporosis. The age of the osteoporosis group was older than that of the non-osteoporosis group [osteoporosis group (72.47±6.89) years old, non-osteoporosis group (68.73±6.34) years old, and the difference was statistically significant, t=-11.67, P<0.05]. The waist circumference, alanine aminotransferase (ALT), creatinine (CR), blood urea nitrogen (BUN) and uric acid (UA) in the non-osteoporosis group were higher than those in the osteoporosis group, and the difference was statistically significant (all P<0.05). The levels of high-density lipoprotein (HDL)[osteoporosis group (1.34±0.35) mol/L, non-osteoporosis group (1.41±0.35) mol/L, t=-4.51, P<0.05] and alkaline phosphatase (ALP)[osteoporosis group (88.46±25.65) mol/L, osteoporosis group (94.56±32.32) mol/L, t=-4.79, P<0.05] in the osteoporosis group were lower than those in the non-osteoporosis group.Low awareness of the knowledge of osteoporosis risk factors(smoking, drinking coffee, high salt and drinking alcohol are 47.28%, 24.15%, 47.79% and 44.90%, respectively), diagnosis and treatment(The symptoms, prognosis, screening methods, medication time and follow-up screening time of osteoporosis were 26.87%, 17.88%, 21.77%, 6.65% and 15.99%, respectivel) and prevention(exercise mode, high calcium food, optimal age of calcium supplementation, the effect of vitamin D on OP, and the appropriate amount of milk to prevent osteoporosis were 33.16%, 42.01%, 13.27%, 12.07%, 9.01%, respectively) were in Jiuting Town. In conclusion, the prevalent rate of OP in the elderly ≥60 years old in Jiuting Town is 45.89%.The main risk factors are female and advanced age. Drinking tea, dairy products, combination of meat and vegetable, taking calcium, physical exercise and sun exposure were the protective factors for osteoporosis. The awareness rate of osteoporosis related knowledge is low, and health education should be strengthened in order to control and prevent the occurrence and development of osteoporosis.

Objective:To investigate the clinical and genetic features of patients with spastic paraplegia and psychomotor retardation with or without seizures (SPPRS) caused by HACE1 gene mutation. Methods:Clinical data, auxiliary examination and genetic test results of a child with SPPRS caused by HACE1 gene mutation who was admitted to Henan Children′s Hospital in April 2019 were collected. The clinical and genotypic characteristics of children with SPPRS were summarized by searching the relevant literature up to June 2024, retrieved from CNKI, Wanfang and PubMed databases with the terms of " HACE1" "SPPRS" "seizures" "spastic paraplegia". Results:The patient was a 11 months and 20 days old male, with a clinical phenotype including global developmental delay, leg spastic tremor, frequent epileptic seizures, obesity, and concurrent urethral malformation. Brain magnetic resonance imaging (MRI) showed enlarged bilateral ventricles, hypoplastic corpus callosum, delayed myelination. Genetic test results revealed compound heterozygous variants c.994C>T (p.R332 *) and c.1679-2A>G in the HACE1 gene (according to the transcript NM_020771), respectively inherited from his mother and father, with c.1679-2A>G being a newly reported variant. A total of 6 English literatures reported 21 SPPRS patients in 11 families, and HACE1 gene mutations were mainly characterized by nonsense mutations. The main clinical manifestations included global developmental delay (21 cases), movement disorders (21 cases), intellectual disabilities (18 cases), seizures (13 cases), obesity (13 cases), skeletal abnormalities (11 cases), microcephaly (9 cases), ocular abnormalities (9 cases), distinctive facial features (5 cases), sensorineural hearing loss (5 cases), and short stature (3 cases). MRI predominantly showed hypoplasia of the corpus callosum, ventricular dilation, paucity of white matter and cerebral atrophy. There were no clear genotype-phenotype correlations. A total of 13 HACE1 gene mutations were reported, including 9 nonsense mutations, 2 frameshift mutations, 1 in-frame mutation, and 1 missense mutation. Among the 11 families, only 2 families with 5 patients were caused by compound heterozygous mutations, c.1852_1853del (p.L832del) and c.454C>T (p.Q152 *), c.2242C>T (p.R748 *) and c.2019_2020insTTTAGGTATTTTTAGGTATT (p.P674fs). The other 16 patients in 9 families were caused by homozygous mutations of the remaining 9 mutations. Conclusions:SPPRS is rare and usually occurs in infancy. The main clinical manifestations include comprehensive developmental delay, movement disorders, epilepsy, etc. Currently, no clear genotype-phenotype correlation has been found. The c.1679-2A>G variant of the HACE1 gene is an unreported variant and enriches the mutation spectrum of the HACE1 gene.

Objective:To construct a predictive model for intensive care unit (ICU) and in-hospital mortality risk in patients with traumatic brain injury (TBI) and validate its performance.Methods:A retrospective cohort study was conducted to analyze the clinical data of 3 907 patients with TBI published until May 2018 in the eICU Collaborative Research Database v2.0 (eICU-CRD v2.0), including 2 397 males and 1 510 females, aged 18-92 years [63.0(43.0, 79.0)years]. According to whether the patients died in ICU or at hospital stay, they were divided into ICU survival group ( n=3 575) and ICU mortality group ( n=332), and hospital survival group ( n=3 413) and hospital mortality group ( n=494). The general data, admission diagnosis, laboratory tests, therapeutic interventions, and clinical outcomes were extracted as variables of interest. Univariate analysis and multivariate Logistic regression analysis were conducted on both the survival groups and the mortality groups to identify the independent risk factors that affect ICU and in-hospital mortality in TBI patients, based on which a Logistic regression prediction model was constructed and represented by Nomograms. The extracted dataset was randomly divided into training set ( n=2 735) and validation set ( n=1 172) with a ratio of 7∶3, and was applied for internal validation of the of the predictive model. Meanwhile, the data of TBI patients in the MIMIC-III v1. 4 database were extracted for external validation of the predictive model. The area under the curve (AUC) of the receiver operating characteristic (ROC) curve was used for discriminability evaluation of the model, and the Hosmer-Lemeshow (H-L) goodness of fit test and calibration curve were used for calibration evaluation of the model. Results:The statistically significant variables identified in the univariate analysis were included in the multivariate logistic regression analysis of ICU mortality and in-hospital mortality risk. The results revealed that acute physiology and chronic health evaluation IV (APACHE IV) score ( OR=1.04, 95% CI 1.03, 1.04, P<0.01), Glasgow coma scale (GCS) ( OR=0.66, 95% CI 0.59, 0.73, P<0.01), cerebral hernia formation ( OR=6.91, 95% CI 3.13, 15.26, P<0.01), international normalized ratio (INR) ( OR=1.33, 95% CI 1.09, 1.62, P<0.01), use of hypertonic saline ( OR=0.45, 95% CI 0.21 0.94, P<0.05), and use of vasoactive agents ( OR=2.19, 95% CI 1.36, 3.52, P<0.01) were independent risk factors for ICU mortality in TBI patients. The age (with 10 years as a grade) ( OR=1.28, 95% CI 1.17, 1.40, P<0.01), APACHE IV score ( OR=1.03, 95% CI 1.02, 1.04, P<0.01), GCS ( OR=0.75, 95% CI 0.71, 0.80, P<0.01), cerebral hernia formation ( OR=6.44, 95% CI 2.99, 13.86, P<0.01), serum creatinine level ( OR=1.07, 95% CI 1.01, 1.15, P<0.05), INR ( OR=1.49, 95% CI 1.20, 1.85, P<0.01), use of hypertonic saline ( OR=0.41, 95% CI 0.21, 0.80, P<0.01), and use of vasoactive agents ( OR=2.27, 95% CI 1.46, 3.53, P<0.01) were independent risk factors of in-hospital mortality of TBI patients. Based on the forementioned independent risk factors for ICU mortality, the model equation was constructed: Logit P (ICU)=7.12+0.03×"APACHE IV score"-0.42×"GCS"+1.93×"cerebral hernia formation"+0.28×"INR"-0.81×"use of hypertonic saline"+0.79×"use of vasoactive agents". Based on the forementioned independent risk factors for in-hospital mortality, the model equation was constructed: Logit P (in-hospital)=2.75+0.25×"age"(with 10 years as a grade)+0.03×"APACHE IV score"-0.28×"GCS"+1.86×"cerebral hernia formation"+0.07×"serum creatinine level"+0.40×"INR"-0.90×"use of hypertonic saline"+0.82×"use of vasoactive agents". In the prediction model for ICU mortality, the AUC of the training set and validation set was 0.95 (95% CI 0.94, 0.97) and 0.91 (95% CI 0.87, 0.95). The result of H-L goodness of fit test of the training set was P=0.495 with the average absolute error in the calibration curve of 0.003, while the result of H-L goodness of fit test of the validation set was P=0.650 with the average absolute error in the calibration curve of 0.012. In the prediction model for in-hospital mortality, the AUC of the training set and validation set was 0.91 (95% CI 0.89, 0.93) and 0.91(95% CI 0.88, 0.94). The result of H-L goodness of fit test of the training set was P=0.670 with the average absolute error in the calibration curve of 0.006, while the result of H-L goodness of fit test of the validation set was P=0.080 with the average absolute error in the calibration curve of 0.021. In the external validation set of ICU mortality risk, the AUC of the prediction model was 0.88 (95% CI 0.86, 0.90), while the result of H-L goodness of fit test was P=0.205 with the average absolute error in the calibration curve of 0.031. In the external validation set of in-hospital mortality risk, the AUC of the prediction model was 0.88 (95% CI 0.85, 0.91), while the result of H-L goodness of fit test was P=0.239 with the average absolute error in the calibration curve of 0.036. The internal and external validation of the model indicated that both the prediction models for ICU and in-hospital mortality had good discriminability and calibration. Conclusion:The ICU mortality prediction model constructed by APACHE IV score, GCS, cerebral hernia formation, use of hypertonic saline, vasoactive agents use of and INR, and the in-hospital mortality prediction model constructed by age grading, APACHE IV score, GCS, cerebral hernia formation, serum creatinine level, hypertonic saline use of, use of vasoactive agents and INR can predict the mortality risk of TBI patients well.

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.