Objective： To investigate the risk factors related to the development of pressure sores in critically ill surgical patients and to establish a basis for the formulation of effective precautions. Methods： A questionn...Objective： To investigate the risk factors related to the development of pressure sores in critically ill surgical patients and to establish a basis for the formulation of effective precautions. Methods： A questionnaire regarding the factors for pressure sores in critically ill surgical patients was created using a case control study with reference to the pertinent literature. After being exam- ined and validated by experts, the questionnaire was used to collect data about critically ill surgical patients in a grade A tertiary hospital. Among the 47 patients enrolled into the study, the 14 who developed nosocomial pressure sores were allocated to the pressure sore group, and the remaining 33 patients who met the inclusion criteria and did not exhibit pressure sores were allocated to the control group. Univariate and multivariate logistic regression analyses were employed to examine the differences in 22 indicators between the two groups in an attempt to identify the risk factors for pressure sores. Results： According to the univariate analyses, the maximum value of lactic acid in the arterial blood, the number of days of norepinephrine use, the number of days of mechanical ventilation, the number of days of blood purification, and the number of days of bowel incontinence were statistically greater in the pressure sore group than in the control group （P〈0.05）. The multivariate logistic regression analysis revealed that the number of days of norepinephrine use and the level of lactic acid in the arterial blood were high risk-factors for pressure sores （P〈0.05）. Conclusions： The best method for preventing and control pressure sores in surgical critically ill patients is to strongly emphasize the duration of the critical status and to give special attention to patients in a continuous state of shock. The adoption of measures specific to high-risk patient groups and risk factors, including the active control of primary diseases and the application of decompression measures during the treatment of the patients, are helpful for improving the quality of care in the prevention and control of pressure sores in critically ill patients.展开更多
To the Editor:The standardized management of pain–agitation–delirium(PAD)represents a fundamental component of clinical practice in intensive care units(ICUs).[1]Evidence-based analgesia and sedation strategies not ...To the Editor:The standardized management of pain–agitation–delirium(PAD)represents a fundamental component of clinical practice in intensive care units(ICUs).[1]Evidence-based analgesia and sedation strategies not only alleviate patients’physiological discomfort and psychological distress,but also significantly reduce mechanical ventilation duration,improve long-term prognosis,and optimize healthcare resource allocation.[1,2]Equally crucial is delirium management,as evidenced by studies demonstrating that delirium duration independently predicts mortality risk,hospital stay length,healthcare expenditures,and acquired dementia incidence.展开更多
Intensive care unit-acquired weakness(ICU-AW)is a common complication in critically ill patients and is associated with a variety of adverse outcomes.These include the need for prolonged mechanical ventilation and ICU...Intensive care unit-acquired weakness(ICU-AW)is a common complication in critically ill patients and is associated with a variety of adverse outcomes.These include the need for prolonged mechanical ventilation and ICU stay;higher ICU,in-hospital,and 1-year mortality;and increased in-hospital costs.ICU-AW is associated with multiple risk factors including age,underlying disease,severity of illness,organ failure,sepsis,immobilization,receipt of mechanical ventilation,and other factors related to critical care.The pathological mechanism of ICUAW remains unclear and may be considerably varied.This review aimed to evaluate recent insights into ICU-AW from several aspects including risk factors,pathophysiology,diagnosis,and treatment strategies;this provides new perspectives for future research.展开更多
P450 enzymes-catalyzed aromatic hydroxylation plays an important role in detoxification,biosynthesis,and potential carcinogenic effect of aromatic compounds.Though it has been explored for decades,the actual process o...P450 enzymes-catalyzed aromatic hydroxylation plays an important role in detoxification,biosynthesis,and potential carcinogenic effect of aromatic compounds.Though it has been explored for decades,the actual process of aromatic hydroxylation and mechanism of regioselectivity catalyzed by cytochrome P450 monooxygenases remained ambiguous.Here,we have resolved these issues.With a stable chiral organofluorine probe,and especially with X-ray data of two isolated arene oxides derivatives,we demonstrate that an arene oxide pathway is definitely involved in P450-catalyzed aromatic hydroxylation.By the capture,isolation,identification and reactivity exploration of the arene 1,2-oxide and arene 2,3-oxide intermediates,together with advanced QM calculations,the mechanism of how two intermediates go to the same product has been elucidated.In addition to the model substrate,we also confirmed that an arene oxide intermediate is involved in the P450-catalyzed hydroxylation pathway of a natural product derivative methyl cinnamate,which indicates that this intermediate appears to be universal in P450-catalyzed aromatic hydroxylation.Our work not only provides the most direct evidence for the arene oxide pathway and new insights into the regioselectivity involved in P450-catalyzed aromatic hydroxylation,but also supplies a new synthetic approach to achieve the dearomatization of aromatic compounds.展开更多
Mitochondrial cytopathies are characterized by energy failure within the cellular system.These disorders exhibit a wide range of clinical presentations and are highly heterogeneous.The mitochondrial diseases include m...Mitochondrial cytopathies are characterized by energy failure within the cellular system.These disorders exhibit a wide range of clinical presentations and are highly heterogeneous.The mitochondrial diseases include mitochondrial encephalopathy,lactic acidosis,and stroke-like episodes (MELAS).MELAS syndrome has various manifestations,including stroke-like episodes,dementia,epilepsy,lactic acidemia,myopathy,recurrent headaches,hearing impairment,diabetes,and short stature.The initial report on MELAS syndrome was published by Pavlakis et al in 1984.^([1])展开更多
Lung transplantation (LT)has emerged as a crucial life-saving option for critically ill patients with severe coronavirus disease 2019 (COVID-19)-related acute respiratory distress syndrome (ARDS) or irreversible lung ...Lung transplantation (LT)has emerged as a crucial life-saving option for critically ill patients with severe coronavirus disease 2019 (COVID-19)-related acute respiratory distress syndrome (ARDS) or irreversible lung injury.[1]Intensive care unit-acquired weakness (ICU-AW)is a prevalent complication in critically ill patients.[2] The recovery of recipients undergoing LT for COVID-19-related respiratory failure may face impediments due to ICU-AW,which negatively affects early mobilization and functional improvement. This study describes two cases of successful bilateral LT for severe COVID-19-related ARDS with the occurrence of ICU-AW and subsequent successful discharge.展开更多
BACKGROUND: Notch-1/NF-κB signaling plays a key role in the cecal ligation and puncture(CLP)-induced sepsis. This study aims to investigate the intervention effects of microRNA-34a(miR-34a) lentivirus regulating Notc...BACKGROUND: Notch-1/NF-κB signaling plays a key role in the cecal ligation and puncture(CLP)-induced sepsis. This study aims to investigate the intervention effects of microRNA-34a(miR-34a) lentivirus regulating Notch-1/NF-κB signaling pathway on lipopolysaccharide(LPS)-induced human umbilical vein endothelial cells(HUVEC).METHODS: HUVEC were divided into four groups as the following: they were infected with negative control lentivirus(NC group) or miR-34a lentivirus(OE group); LPS(1 g/mL) was added on the third day on the basis of NC group and OE group for 24 hours(NC+LPS group or OE+LPS group). The levels of TNF-α, IL-1β, IL-6, and IL-10 in the cell supernatants, and the mRNA and protein expression of Notch-1 and NF-κB in the HUVEC were evaluated.RESULTS: After 24 hours, the levels of TNF-α, IL-1β, IL-6 in the cell supernatants and the protein expression of NF-κB from NC+LPS group were significantly higher than those of NC group, but IL-10 level and the protein expression of Notch-1 in NC+LPS group were the opposite. After intervention of miR-34a lentivirus, the cell supernatants TNF-α and the protein expression of NF-κB in OE+LPS group after 24 hours markedly decreased compared to NC+LPS group. While the cell supernatants IL-1β and IL-6 and the mRNA expression of NF-κB slightly decreased in OE+LPS group, IL-10 and the mRNA and protein expression of Notch-1 were the opposite.CONCLUSION: miR-34a regulating Notch-1/NF-κB signaling pathway can reduce the HUVEC damage caused by LPS stimulation.展开更多
Dear editor,Extracorporeal membrane oxygenation(ECMO)is a modality of extracorporeal life support that allows for temporary support in pulmonary and/or cardiac failure refractory to conventional therapy.[1]ECMO use ha...Dear editor,Extracorporeal membrane oxygenation(ECMO)is a modality of extracorporeal life support that allows for temporary support in pulmonary and/or cardiac failure refractory to conventional therapy.[1]ECMO use has been exponentially increasing over the last decade and is now considered a mainstream lifesaving treatment modality in critical care medicine.Many studies report ECMO use in patients with acute respiratory distress syndrome refractory to conventional clinical support,in-hospital cardiac arrest,and cardiogenic refractory shock.[1-3]Herein,we report the use of veno-arterial ECMO(VA-ECMO)in the first successful combined lung-liver transplantation(CLLT)patient in China.展开更多
Articular cartilage damage is a universal health problem.Despite recent progress,chondrocyte dedifferentiation has severely compromised the clinical outcomes of cell-based cartilage regeneration.Loss-of-function chang...Articular cartilage damage is a universal health problem.Despite recent progress,chondrocyte dedifferentiation has severely compromised the clinical outcomes of cell-based cartilage regeneration.Loss-of-function changes are frequently observed in chondrocyte expansion and other pathological conditions,but the characteristics and intermediate molecular mechanisms remain unclear.In this study,we demonstrate a time-lapse atlas of chondrocyte dedifferentiation to provide molecular details and informative biomarkers associated with clinical chondrocyte evaluation.We performed various assays,such as single-cell RNA sequencing(scRNA-seq),live-cell metabolic assays,and assays for transposase-accessible chromatin with high-throughput sequencing(ATAC-seq),to develop a biphasic dedifferentiation model consisting of early and late dedifferentiation stages.Early-stage chondrocytes exhibited a glycolytic phenotype with increased expression of genes involved in metabolism and antioxidation,whereas late-stage chondrocytes exhibited ultrastructural changes involving mitochondrial damage and stress-associated chromatin remodeling.Using the chemical inhibitor BTB06584,we revealed that early and late dedifferentiated chondrocytes possessed distinct recovery potentials from functional phenotype loss.Notably,this two-stage transition was also validated in human chondrocytes.An image-based approach was established for clinical use to efficiently predict chondrocyte plasticity using stage-specific biomarkers.Overall,this study lays a foundation to improve the quality of chondrocytes in clinical use and provides deep insights into chondrocyte dedifferentiation.展开更多
Malignant hyperthermia(MH)is a genetic disorder of skeletal muscle cells that affects muscle cytoplasmic calcium homeostasis,with high mortality and low morbidity.Generally,it presents with non-specific signs of a hyp...Malignant hyperthermia(MH)is a genetic disorder of skeletal muscle cells that affects muscle cytoplasmic calcium homeostasis,with high mortality and low morbidity.Generally,it presents with non-specific signs of a hypermetabolic response,including high fever,tachycardia,and elevated end-tidal carbon dioxide(ETCO_(2)).The successful treatment lies in the timely recognition and early use of dantrolene.[1]As an inhibitor of Ca2+release through ryanodine receptor(RYR)channels,the skeletal muscle relaxant dantrolene has proven to be both a valuable experimental probe of intracellular Ca2+signaling and a lifesaving treatment for MH.[2]Dominant mutations in the skeletal muscle RYR1 gene are well-recognized causes of both malignant hyperthermia susceptibility(MHS)and central core disease(CCD).展开更多
BACKGROUND Perforated peptic ulcer(PPU)is a common emergency surgical condition and a significant cause of morbidity and mortality worldwide.While advances in surgical techniques have improved outcomes for patients wi...BACKGROUND Perforated peptic ulcer(PPU)is a common emergency surgical condition and a significant cause of morbidity and mortality worldwide.While advances in surgical techniques have improved outcomes for patients with PPU,many factors still affect postoperative hospital stay and overall prognosis.One potential factor is the serum albumin(SA)level,a widely utilized marker of nutritional status that has been associated with length of stay and complications in various surgical procedures.AIM To clarify the correlation of SA level on postoperative day 2 with hospital length of stay(HLOS)in patients undergoing emergency surgery for perforated peptic ulcer(PPU).METHODS We retrospectively collected and analyzed clinical baseline data,including blood routine and SA levels,of patients who underwent emergency PPU surgery and postoperative treatment at the Lingnan Hospital,the Third Affiliated Hospital of Sun Yat-sen University between December 2012 and September 2021.Patients were grouped according to HLOS with 7 d as the cut-off value,and relevant indicators were analyzed using SPSS 26.0.RESULTS Of the 37 patients undergoing emergency surgery for PPU referred to our department,33 had gastric and 4 had duodenal ulcer perforation.The median HLOS was 10 d.There were 8 patients in the≤7-d group(median HLOS:7 d)and 29 patients in the>7-d group(median HLOS:10 d).The≤7-d group had markedly higher SA on postoperative day 2 than the>7-d group(37.7 g/L vs 32.6g/L;P<0.05).The SA level on postoperative day 2 was a protective factor for patients with HLOS>7 d(Odds ratio=0.629,P=0.015).The cut-off of SA on postoperative day 2 was 30.6g/L,with an area under the curve of 0.86 and a negative predictive value of 100%for the prediction of HLOS≤7 d.CONCLUSION The SA level on postoperative day 2 was associated with the HLOS in patients undergoing emergency surgery for PPU.The pre-and post-operative albumin levels should be monitored,and infusion of human SA should be considered in a timely manner.展开更多
Postpartum inferior vena cava (IVC) thrombosis is a rare,but potentially life-threatening disorder.Here we reported one case of the youngest woman to date who presented with massive IVC thrombus extending from deep ve...Postpartum inferior vena cava (IVC) thrombosis is a rare,but potentially life-threatening disorder.Here we reported one case of the youngest woman to date who presented with massive IVC thrombus extending from deep veins of the right leg to the level of the 11th thoracic vertebra,associated with asymptomatic pulmonary embolism.展开更多
Dear editor,Pupillary abnormalities, i.e., mydriasis, pupillary arefl exia, and/or anisocoria, may indicate the occurrence of acute clinical events in intensive care units (ICUs),which are particularly seen in severe ...Dear editor,Pupillary abnormalities, i.e., mydriasis, pupillary arefl exia, and/or anisocoria, may indicate the occurrence of acute clinical events in intensive care units (ICUs),which are particularly seen in severe patients with brain and/or cervical spinal cord injury. The pathophysiology of benign episodic mydriasis is still not completely clear. We present a patient with severe burns presented with temporary alternating bilateral pupil enlargement accompanied by paroxysmal increases in respiration,heart rate, and blood pressure.展开更多
Autonomously self-propelled nanoswimmers represent the nextgeneration nano-devices for bio-and environmental technology.However,current nanoswimmers generate limited energy output and can only move in short distances ...Autonomously self-propelled nanoswimmers represent the nextgeneration nano-devices for bio-and environmental technology.However,current nanoswimmers generate limited energy output and can only move in short distances and duration,thus are struggling to be applied in practical challenges,such as living cell transportation.Here,we describe the construction of biodegradable metal-organic framework based nanobots with chemically driven buoyancy to achieve highly efficient,long-distance,directional vertical motion to“find-and-fetch”target cells.Nanobots surface-functionalized with antibodies against the cell surface marker carcinoembryonic antigen are exploited to impart the nanobots with specific cell targeting capacity to recognize and separate cancer cells.We demonstrate that the self-propelled motility of the nanobots can sufficiently transport the recognized cells autonomously,and the separated cells can be easily collected with a customized glass column,and finally regain their full metabolic potential after the separation.The utilization of nanobots with easy synthetic pathway shows considerable promise in cell recognition,separation,and enrichment.展开更多
Introduction: Intraoperative cardiovascular complications were previously demonstrated in relation to high sympathetic nervous system outflow or stimulation of the vagal nerve nucleus during theneurosurgical procedure...Introduction: Intraoperative cardiovascular complications were previously demonstrated in relation to high sympathetic nervous system outflow or stimulation of the vagal nerve nucleus during theneurosurgical procedures on brain tumors. Main Symptoms and Important Clinical Findings: We are presenting clinical case of 13-year-old girl who suffered from midbrain glioma and developed life threatening cardiovascular events during neurosurgical procedure after surgicel hemostatic agent application. Therapeutic Interventions and Outcomes: Cardiovascular stability has been restored after immediate removal of surgicel from the operating field. We believe that it might be related to direct application of the surgicel hemostatic agent.展开更多
Introduction: Acute appendicitis represents an urgent surgical condition, requiring the removal of the vermiform appendix. Laparoscopy is the standard surgical approach. This study aimed to outline the epidemiological...Introduction: Acute appendicitis represents an urgent surgical condition, requiring the removal of the vermiform appendix. Laparoscopy is the standard surgical approach. This study aimed to outline the epidemiological, clinical, therapeutic, and outcome characteristics of patients undergoing laparoscopic surgery for acute appendicitis. Patients and Methods: A descriptive, retrospective analysis was carried out in the Emergency and Digestive Surgery departments of the University Hospital Center of Brazzaville, spanning two years from January 1, 2021, to December 31, 2022. The study included all patients who underwent laparoscopic surgery for non-complicated acute appendicitis. Results: The study included 12 cases of non-complicated acute appendicitis treated with urgent laparoscopy. The mean age of the patients was 37 ± 8.9 years, with a sex ratio of 0.7. The predominant symptom leading to consultation was pain in the right iliac fossa, with an average time to consultation of 6.4 ± 5.7 hours. Patient histories included diabetes in one case, obesity in two cases, and one case of prior abdominoplasty. During surgery, a phlegmonous appendix was observed in nine patients. The average duration of hospital stay was 3.6 ± 1.3 days, with all patients experiencing uncomplicated recoveries. Conclusion: The practice of emergency laparoscopic appendectomy is still relatively infrequent in our setting and presents an ongoing challenge.展开更多
In this case series we present 3 cases of nasogastric tube misplacement in tracheostomy patients. Although considered safe and it being a common procedure nasogastric tube misplacement can lead to serious and life-thr...In this case series we present 3 cases of nasogastric tube misplacement in tracheostomy patients. Although considered safe and it being a common procedure nasogastric tube misplacement can lead to serious and life-threatening complications. We present three cases of nasogastric tube misplacement in tracheostomized patients. One of the cases presented suffered from pneumothorax. Different time intervals between procedures in these different cases resulted in similar results. We would like to emphasize the importance of due conformation of correct placement of the nasogastric tube in the tracheostomy patient as well as to suggest that over inflation of the balloon securing the tracheostomy apparatus in place during nasogastric tube placement, might prevent misplacement. Nasogastric tube placement in tracheostomized patients has potential for serious complications. As such maintaining safe practice procedure is essential. Considering over inflation of the tracheostomy apparatus balloon might be beneficial as well, by preventing entry of NGT into the trachea.展开更多
Biotin(vitamin H or B7)is a sulfur-containing intermediate of fatty acids,and functions as an indispensable co-enzyme across the three domains of life.In general,biotin synthesis occurs in bac-teria,fungi and plants,r...Biotin(vitamin H or B7)is a sulfur-containing intermediate of fatty acids,and functions as an indispensable co-enzyme across the three domains of life.In general,biotin synthesis occurs in bac-teria,fungi and plants,rather than mammals and birds.In certain bacterial pathogens like the tuberculosis-causing agent,Mycobac-terium[1]and the life-threatening causative,Francisella[2],it also acts as a nutritional restriction factor having a critical role in bac-terial pathogenesis.Apart from hypervirulence of the two recalci-trant ESKAPE members,Klebsiella pneumoniae[3]and Pseudomonas aeruginosa[4,5],biotin biosynthesis was recently demonstrated to determine Acinetobacter baumannii polymyxin resistance[6].As an energetically-expansive molecule whose de novo biosynthesis requires 15-20 ATP equivalents,a number of diversified bacteria have evolved different regulated mechanisms for biotin production(perhaps salvage).The bifunctional enzyme BirA of E.coli is a paradigm regulator of biotin synthesis[7].In addition,two distinct regulatory mechanisms are functionally defined.Namely,they include the BioR repressor restricted to a-proteobacte ria[8],and the BioQ regulator found in Corynebac-terium glutamicum and Mycobacterium smegmatis[9].展开更多
Background Pediatric lung transplant(pLTX)is a rare procedure globally;its characteristics and survival outcomes in China remain unknown.Methods This retrospective study analyzed data from pLTX recipients aged≤17 yea...Background Pediatric lung transplant(pLTX)is a rare procedure globally;its characteristics and survival outcomes in China remain unknown.Methods This retrospective study analyzed data from pLTX recipients aged≤17 years between January 2019 and Decem-ber 2023 from the China Lung Transplantation Registry.Pre-,intra-,and post-operative characteristics were described and compared between children aged 2-11 years and 12-17 years and between pLTX conducted in centers with high and low transplant volumes.The Kaplan-Meier method was used to estimate the postoperative survival rates and 95%confidence intervals(CIs).One-year postoperative survival rates were compared between pediatric and adult lung transplant(LTX)patients via log-rank tests.Results Between 2019 and 2023,63 transplants were performed in 62 pediatric patients,accounting for 1.8%of the total LTX in China.The primary indication for pLTX was bronchiolitis obliterans syndrome(46.0%),followed by cystic fibrosis(12.7%)and idiopathic pulmonary arterial hypertension(11.1%).Infection was the most common complication after pLTX(63.9%),and the incidence of bronchial anastomotic stenosis was slightly higher among recipients aged 2-11 years than among those aged 12-17 years(14.3%vs.2.9%,P=0.244).High-volume hospitals had a higher incidence of infections(72.7%vs.41.2%,P=0.021)and primary graft failure(20.0%vs.5.9%,P=0.260)among pediatric recipients.However,acute rejection was exclusively observed in low-volume hospitals(0.0%vs.17.6%,P=0.018).The in-hospital mortality rate was 16.1%(95%CI=6.7-25.5).The 30-day and one-year survival rates after pLTX were 93.5%(95%CI=87.6-99.9)and 80.6%(95%CI=71.4-91.1),respectively,and were significantly higher than those of adult recipients(82.0%and 58.7%,all P<0.05).Conclusions This research identified the trends,indications,donor and recipient characteristics,and complications of pLTX in China.Despite its small size,pLTX is growing gradually and has favorable outcomes.Future research on the long-term follow-up of pLTX recipients is needed to identify factors associated with the prognosis of pLTX patients.展开更多
Tetracyclines,a group of antimicrobial agents targeting protein synthesis,have been extensively used in agricultural,veterinary,and clinic settings[1].The sporadic rise in tetracycline resistance is partially due to t...Tetracyclines,a group of antimicrobial agents targeting protein synthesis,have been extensively used in agricultural,veterinary,and clinic settings[1].The sporadic rise in tetracycline resistance is partially due to the occurrence of efflux pumps and/or ribosome protection[1,2].The growing body of tetracycline-inactivating enzymes(e.g.,TetX(X1 to X4)[3,4]and Tet(47 to 55)[5])represents an alternative mechanism for tetracycline resistance,and threatens the renewed interest of tigecycline as a last-resort defense against lethal infections with carbapenem-resistant Enterobacteriaceae and Acinetobacter species.展开更多
文摘Objective： To investigate the risk factors related to the development of pressure sores in critically ill surgical patients and to establish a basis for the formulation of effective precautions. Methods： A questionnaire regarding the factors for pressure sores in critically ill surgical patients was created using a case control study with reference to the pertinent literature. After being exam- ined and validated by experts, the questionnaire was used to collect data about critically ill surgical patients in a grade A tertiary hospital. Among the 47 patients enrolled into the study, the 14 who developed nosocomial pressure sores were allocated to the pressure sore group, and the remaining 33 patients who met the inclusion criteria and did not exhibit pressure sores were allocated to the control group. Univariate and multivariate logistic regression analyses were employed to examine the differences in 22 indicators between the two groups in an attempt to identify the risk factors for pressure sores. Results： According to the univariate analyses, the maximum value of lactic acid in the arterial blood, the number of days of norepinephrine use, the number of days of mechanical ventilation, the number of days of blood purification, and the number of days of bowel incontinence were statistically greater in the pressure sore group than in the control group （P〈0.05）. The multivariate logistic regression analysis revealed that the number of days of norepinephrine use and the level of lactic acid in the arterial blood were high risk-factors for pressure sores （P〈0.05）. Conclusions： The best method for preventing and control pressure sores in surgical critically ill patients is to strongly emphasize the duration of the critical status and to give special attention to patients in a continuous state of shock. The adoption of measures specific to high-risk patient groups and risk factors, including the active control of primary diseases and the application of decompression measures during the treatment of the patients, are helpful for improving the quality of care in the prevention and control of pressure sores in critically ill patients.
基金supported by a grant from 1.3.5 project for disciplines of excellence,West China Hospital,Sichuan University(No.ZYGD23012).
文摘To the Editor:The standardized management of pain–agitation–delirium(PAD)represents a fundamental component of clinical practice in intensive care units(ICUs).[1]Evidence-based analgesia and sedation strategies not only alleviate patients’physiological discomfort and psychological distress,but also significantly reduce mechanical ventilation duration,improve long-term prognosis,and optimize healthcare resource allocation.[1,2]Equally crucial is delirium management,as evidenced by studies demonstrating that delirium duration independently predicts mortality risk,hospital stay length,healthcare expenditures,and acquired dementia incidence.
基金supported by grants from the National Natural Science Foundation of China(grant number:82072201).
文摘Intensive care unit-acquired weakness(ICU-AW)is a common complication in critically ill patients and is associated with a variety of adverse outcomes.These include the need for prolonged mechanical ventilation and ICU stay;higher ICU,in-hospital,and 1-year mortality;and increased in-hospital costs.ICU-AW is associated with multiple risk factors including age,underlying disease,severity of illness,organ failure,sepsis,immobilization,receipt of mechanical ventilation,and other factors related to critical care.The pathological mechanism of ICUAW remains unclear and may be considerably varied.This review aimed to evaluate recent insights into ICU-AW from several aspects including risk factors,pathophysiology,diagnosis,and treatment strategies;this provides new perspectives for future research.
文摘P450 enzymes-catalyzed aromatic hydroxylation plays an important role in detoxification,biosynthesis,and potential carcinogenic effect of aromatic compounds.Though it has been explored for decades,the actual process of aromatic hydroxylation and mechanism of regioselectivity catalyzed by cytochrome P450 monooxygenases remained ambiguous.Here,we have resolved these issues.With a stable chiral organofluorine probe,and especially with X-ray data of two isolated arene oxides derivatives,we demonstrate that an arene oxide pathway is definitely involved in P450-catalyzed aromatic hydroxylation.By the capture,isolation,identification and reactivity exploration of the arene 1,2-oxide and arene 2,3-oxide intermediates,together with advanced QM calculations,the mechanism of how two intermediates go to the same product has been elucidated.In addition to the model substrate,we also confirmed that an arene oxide intermediate is involved in the P450-catalyzed hydroxylation pathway of a natural product derivative methyl cinnamate,which indicates that this intermediate appears to be universal in P450-catalyzed aromatic hydroxylation.Our work not only provides the most direct evidence for the arene oxide pathway and new insights into the regioselectivity involved in P450-catalyzed aromatic hydroxylation,but also supplies a new synthetic approach to achieve the dearomatization of aromatic compounds.
文摘Mitochondrial cytopathies are characterized by energy failure within the cellular system.These disorders exhibit a wide range of clinical presentations and are highly heterogeneous.The mitochondrial diseases include mitochondrial encephalopathy,lactic acidosis,and stroke-like episodes (MELAS).MELAS syndrome has various manifestations,including stroke-like episodes,dementia,epilepsy,lactic acidemia,myopathy,recurrent headaches,hearing impairment,diabetes,and short stature.The initial report on MELAS syndrome was published by Pavlakis et al in 1984.^([1])
文摘Lung transplantation (LT)has emerged as a crucial life-saving option for critically ill patients with severe coronavirus disease 2019 (COVID-19)-related acute respiratory distress syndrome (ARDS) or irreversible lung injury.[1]Intensive care unit-acquired weakness (ICU-AW)is a prevalent complication in critically ill patients.[2] The recovery of recipients undergoing LT for COVID-19-related respiratory failure may face impediments due to ICU-AW,which negatively affects early mobilization and functional improvement. This study describes two cases of successful bilateral LT for severe COVID-19-related ARDS with the occurrence of ICU-AW and subsequent successful discharge.
基金supported by a grant from Natural Science Foundation of Zhejiang Province of China(LY14H150003)
文摘BACKGROUND: Notch-1/NF-κB signaling plays a key role in the cecal ligation and puncture(CLP)-induced sepsis. This study aims to investigate the intervention effects of microRNA-34a(miR-34a) lentivirus regulating Notch-1/NF-κB signaling pathway on lipopolysaccharide(LPS)-induced human umbilical vein endothelial cells(HUVEC).METHODS: HUVEC were divided into four groups as the following: they were infected with negative control lentivirus(NC group) or miR-34a lentivirus(OE group); LPS(1 g/mL) was added on the third day on the basis of NC group and OE group for 24 hours(NC+LPS group or OE+LPS group). The levels of TNF-α, IL-1β, IL-6, and IL-10 in the cell supernatants, and the mRNA and protein expression of Notch-1 and NF-κB in the HUVEC were evaluated.RESULTS: After 24 hours, the levels of TNF-α, IL-1β, IL-6 in the cell supernatants and the protein expression of NF-κB from NC+LPS group were significantly higher than those of NC group, but IL-10 level and the protein expression of Notch-1 in NC+LPS group were the opposite. After intervention of miR-34a lentivirus, the cell supernatants TNF-α and the protein expression of NF-κB in OE+LPS group after 24 hours markedly decreased compared to NC+LPS group. While the cell supernatants IL-1β and IL-6 and the mRNA expression of NF-κB slightly decreased in OE+LPS group, IL-10 and the mRNA and protein expression of Notch-1 were the opposite.CONCLUSION: miR-34a regulating Notch-1/NF-κB signaling pathway can reduce the HUVEC damage caused by LPS stimulation.
文摘Dear editor,Extracorporeal membrane oxygenation(ECMO)is a modality of extracorporeal life support that allows for temporary support in pulmonary and/or cardiac failure refractory to conventional therapy.[1]ECMO use has been exponentially increasing over the last decade and is now considered a mainstream lifesaving treatment modality in critical care medicine.Many studies report ECMO use in patients with acute respiratory distress syndrome refractory to conventional clinical support,in-hospital cardiac arrest,and cardiogenic refractory shock.[1-3]Herein,we report the use of veno-arterial ECMO(VA-ECMO)in the first successful combined lung-liver transplantation(CLLT)patient in China.
基金supported by the National Key R&D Program of China(2017YFA0104900)National Natural Science Foundation of China(T2121004,31830029,82002319)。
文摘Articular cartilage damage is a universal health problem.Despite recent progress,chondrocyte dedifferentiation has severely compromised the clinical outcomes of cell-based cartilage regeneration.Loss-of-function changes are frequently observed in chondrocyte expansion and other pathological conditions,but the characteristics and intermediate molecular mechanisms remain unclear.In this study,we demonstrate a time-lapse atlas of chondrocyte dedifferentiation to provide molecular details and informative biomarkers associated with clinical chondrocyte evaluation.We performed various assays,such as single-cell RNA sequencing(scRNA-seq),live-cell metabolic assays,and assays for transposase-accessible chromatin with high-throughput sequencing(ATAC-seq),to develop a biphasic dedifferentiation model consisting of early and late dedifferentiation stages.Early-stage chondrocytes exhibited a glycolytic phenotype with increased expression of genes involved in metabolism and antioxidation,whereas late-stage chondrocytes exhibited ultrastructural changes involving mitochondrial damage and stress-associated chromatin remodeling.Using the chemical inhibitor BTB06584,we revealed that early and late dedifferentiated chondrocytes possessed distinct recovery potentials from functional phenotype loss.Notably,this two-stage transition was also validated in human chondrocytes.An image-based approach was established for clinical use to efficiently predict chondrocyte plasticity using stage-specific biomarkers.Overall,this study lays a foundation to improve the quality of chondrocytes in clinical use and provides deep insights into chondrocyte dedifferentiation.
文摘Malignant hyperthermia(MH)is a genetic disorder of skeletal muscle cells that affects muscle cytoplasmic calcium homeostasis,with high mortality and low morbidity.Generally,it presents with non-specific signs of a hypermetabolic response,including high fever,tachycardia,and elevated end-tidal carbon dioxide(ETCO_(2)).The successful treatment lies in the timely recognition and early use of dantrolene.[1]As an inhibitor of Ca2+release through ryanodine receptor(RYR)channels,the skeletal muscle relaxant dantrolene has proven to be both a valuable experimental probe of intracellular Ca2+signaling and a lifesaving treatment for MH.[2]Dominant mutations in the skeletal muscle RYR1 gene are well-recognized causes of both malignant hyperthermia susceptibility(MHS)and central core disease(CCD).
文摘BACKGROUND Perforated peptic ulcer(PPU)is a common emergency surgical condition and a significant cause of morbidity and mortality worldwide.While advances in surgical techniques have improved outcomes for patients with PPU,many factors still affect postoperative hospital stay and overall prognosis.One potential factor is the serum albumin(SA)level,a widely utilized marker of nutritional status that has been associated with length of stay and complications in various surgical procedures.AIM To clarify the correlation of SA level on postoperative day 2 with hospital length of stay(HLOS)in patients undergoing emergency surgery for perforated peptic ulcer(PPU).METHODS We retrospectively collected and analyzed clinical baseline data,including blood routine and SA levels,of patients who underwent emergency PPU surgery and postoperative treatment at the Lingnan Hospital,the Third Affiliated Hospital of Sun Yat-sen University between December 2012 and September 2021.Patients were grouped according to HLOS with 7 d as the cut-off value,and relevant indicators were analyzed using SPSS 26.0.RESULTS Of the 37 patients undergoing emergency surgery for PPU referred to our department,33 had gastric and 4 had duodenal ulcer perforation.The median HLOS was 10 d.There were 8 patients in the≤7-d group(median HLOS:7 d)and 29 patients in the>7-d group(median HLOS:10 d).The≤7-d group had markedly higher SA on postoperative day 2 than the>7-d group(37.7 g/L vs 32.6g/L;P<0.05).The SA level on postoperative day 2 was a protective factor for patients with HLOS>7 d(Odds ratio=0.629,P=0.015).The cut-off of SA on postoperative day 2 was 30.6g/L,with an area under the curve of 0.86 and a negative predictive value of 100%for the prediction of HLOS≤7 d.CONCLUSION The SA level on postoperative day 2 was associated with the HLOS in patients undergoing emergency surgery for PPU.The pre-and post-operative albumin levels should be monitored,and infusion of human SA should be considered in a timely manner.
文摘Postpartum inferior vena cava (IVC) thrombosis is a rare,but potentially life-threatening disorder.Here we reported one case of the youngest woman to date who presented with massive IVC thrombus extending from deep veins of the right leg to the level of the 11th thoracic vertebra,associated with asymptomatic pulmonary embolism.
文摘Dear editor,Pupillary abnormalities, i.e., mydriasis, pupillary arefl exia, and/or anisocoria, may indicate the occurrence of acute clinical events in intensive care units (ICUs),which are particularly seen in severe patients with brain and/or cervical spinal cord injury. The pathophysiology of benign episodic mydriasis is still not completely clear. We present a patient with severe burns presented with temporary alternating bilateral pupil enlargement accompanied by paroxysmal increases in respiration,heart rate, and blood pressure.
基金supported by the Australian Research Council (ARC, DP210100422)the National Breast Cancer Foundation, Australia (IIRS-22-104)the financial support by the Australian Government Research Training Program Scholarship
文摘Autonomously self-propelled nanoswimmers represent the nextgeneration nano-devices for bio-and environmental technology.However,current nanoswimmers generate limited energy output and can only move in short distances and duration,thus are struggling to be applied in practical challenges,such as living cell transportation.Here,we describe the construction of biodegradable metal-organic framework based nanobots with chemically driven buoyancy to achieve highly efficient,long-distance,directional vertical motion to“find-and-fetch”target cells.Nanobots surface-functionalized with antibodies against the cell surface marker carcinoembryonic antigen are exploited to impart the nanobots with specific cell targeting capacity to recognize and separate cancer cells.We demonstrate that the self-propelled motility of the nanobots can sufficiently transport the recognized cells autonomously,and the separated cells can be easily collected with a customized glass column,and finally regain their full metabolic potential after the separation.The utilization of nanobots with easy synthetic pathway shows considerable promise in cell recognition,separation,and enrichment.
文摘Introduction: Intraoperative cardiovascular complications were previously demonstrated in relation to high sympathetic nervous system outflow or stimulation of the vagal nerve nucleus during theneurosurgical procedures on brain tumors. Main Symptoms and Important Clinical Findings: We are presenting clinical case of 13-year-old girl who suffered from midbrain glioma and developed life threatening cardiovascular events during neurosurgical procedure after surgicel hemostatic agent application. Therapeutic Interventions and Outcomes: Cardiovascular stability has been restored after immediate removal of surgicel from the operating field. We believe that it might be related to direct application of the surgicel hemostatic agent.
文摘Introduction: Acute appendicitis represents an urgent surgical condition, requiring the removal of the vermiform appendix. Laparoscopy is the standard surgical approach. This study aimed to outline the epidemiological, clinical, therapeutic, and outcome characteristics of patients undergoing laparoscopic surgery for acute appendicitis. Patients and Methods: A descriptive, retrospective analysis was carried out in the Emergency and Digestive Surgery departments of the University Hospital Center of Brazzaville, spanning two years from January 1, 2021, to December 31, 2022. The study included all patients who underwent laparoscopic surgery for non-complicated acute appendicitis. Results: The study included 12 cases of non-complicated acute appendicitis treated with urgent laparoscopy. The mean age of the patients was 37 ± 8.9 years, with a sex ratio of 0.7. The predominant symptom leading to consultation was pain in the right iliac fossa, with an average time to consultation of 6.4 ± 5.7 hours. Patient histories included diabetes in one case, obesity in two cases, and one case of prior abdominoplasty. During surgery, a phlegmonous appendix was observed in nine patients. The average duration of hospital stay was 3.6 ± 1.3 days, with all patients experiencing uncomplicated recoveries. Conclusion: The practice of emergency laparoscopic appendectomy is still relatively infrequent in our setting and presents an ongoing challenge.
文摘In this case series we present 3 cases of nasogastric tube misplacement in tracheostomy patients. Although considered safe and it being a common procedure nasogastric tube misplacement can lead to serious and life-threatening complications. We present three cases of nasogastric tube misplacement in tracheostomized patients. One of the cases presented suffered from pneumothorax. Different time intervals between procedures in these different cases resulted in similar results. We would like to emphasize the importance of due conformation of correct placement of the nasogastric tube in the tracheostomy patient as well as to suggest that over inflation of the balloon securing the tracheostomy apparatus in place during nasogastric tube placement, might prevent misplacement. Nasogastric tube placement in tracheostomized patients has potential for serious complications. As such maintaining safe practice procedure is essential. Considering over inflation of the tracheostomy apparatus balloon might be beneficial as well, by preventing entry of NGT into the trachea.
基金supported by the National Key R&D Program of China(2023YFC2308403)the National Science Fund for Distin-guished Young Scholars(32125003)the National Natural Science Foundation of China(32141001).
文摘Biotin(vitamin H or B7)is a sulfur-containing intermediate of fatty acids,and functions as an indispensable co-enzyme across the three domains of life.In general,biotin synthesis occurs in bac-teria,fungi and plants,rather than mammals and birds.In certain bacterial pathogens like the tuberculosis-causing agent,Mycobac-terium[1]and the life-threatening causative,Francisella[2],it also acts as a nutritional restriction factor having a critical role in bac-terial pathogenesis.Apart from hypervirulence of the two recalci-trant ESKAPE members,Klebsiella pneumoniae[3]and Pseudomonas aeruginosa[4,5],biotin biosynthesis was recently demonstrated to determine Acinetobacter baumannii polymyxin resistance[6].As an energetically-expansive molecule whose de novo biosynthesis requires 15-20 ATP equivalents,a number of diversified bacteria have evolved different regulated mechanisms for biotin production(perhaps salvage).The bifunctional enzyme BirA of E.coli is a paradigm regulator of biotin synthesis[7].In addition,two distinct regulatory mechanisms are functionally defined.Namely,they include the BioR repressor restricted to a-proteobacte ria[8],and the BioQ regulator found in Corynebac-terium glutamicum and Mycobacterium smegmatis[9].
基金supported by Top Talent Support Program for young and middle-aged people of Wuxi Health Committee(BJ2023016)the National Key R&D Program"Research on Prevention and Control of Common and Frequent Diseases"in China(2023YFC2507100).
文摘Background Pediatric lung transplant(pLTX)is a rare procedure globally;its characteristics and survival outcomes in China remain unknown.Methods This retrospective study analyzed data from pLTX recipients aged≤17 years between January 2019 and Decem-ber 2023 from the China Lung Transplantation Registry.Pre-,intra-,and post-operative characteristics were described and compared between children aged 2-11 years and 12-17 years and between pLTX conducted in centers with high and low transplant volumes.The Kaplan-Meier method was used to estimate the postoperative survival rates and 95%confidence intervals(CIs).One-year postoperative survival rates were compared between pediatric and adult lung transplant(LTX)patients via log-rank tests.Results Between 2019 and 2023,63 transplants were performed in 62 pediatric patients,accounting for 1.8%of the total LTX in China.The primary indication for pLTX was bronchiolitis obliterans syndrome(46.0%),followed by cystic fibrosis(12.7%)and idiopathic pulmonary arterial hypertension(11.1%).Infection was the most common complication after pLTX(63.9%),and the incidence of bronchial anastomotic stenosis was slightly higher among recipients aged 2-11 years than among those aged 12-17 years(14.3%vs.2.9%,P=0.244).High-volume hospitals had a higher incidence of infections(72.7%vs.41.2%,P=0.021)and primary graft failure(20.0%vs.5.9%,P=0.260)among pediatric recipients.However,acute rejection was exclusively observed in low-volume hospitals(0.0%vs.17.6%,P=0.018).The in-hospital mortality rate was 16.1%(95%CI=6.7-25.5).The 30-day and one-year survival rates after pLTX were 93.5%(95%CI=87.6-99.9)and 80.6%(95%CI=71.4-91.1),respectively,and were significantly higher than those of adult recipients(82.0%and 58.7%,all P<0.05).Conclusions This research identified the trends,indications,donor and recipient characteristics,and complications of pLTX in China.Despite its small size,pLTX is growing gradually and has favorable outcomes.Future research on the long-term follow-up of pLTX recipients is needed to identify factors associated with the prognosis of pLTX patients.
基金supported by National Key R&D Program of China(2017YFD0500202,YF)National Natural Science Foundation of China(31830001,31570027&81772142,YF)
文摘Tetracyclines,a group of antimicrobial agents targeting protein synthesis,have been extensively used in agricultural,veterinary,and clinic settings[1].The sporadic rise in tetracycline resistance is partially due to the occurrence of efflux pumps and/or ribosome protection[1,2].The growing body of tetracycline-inactivating enzymes(e.g.,TetX(X1 to X4)[3,4]and Tet(47 to 55)[5])represents an alternative mechanism for tetracycline resistance,and threatens the renewed interest of tigecycline as a last-resort defense against lethal infections with carbapenem-resistant Enterobacteriaceae and Acinetobacter species.
