Activation of nuclear factor erythroid 2-related factor 2(Nrf2)by Kelch-like ECH-associated protein 1(Keap1)alkylation plays a central role in anti-inflammatory therapy.However,activators of Nrf2 through alkylation of Keap1-Kelch domain have not been identified.Deoxynyboquinone(DNQ)is a natural small molecule discovered from marine actinomycetes.The current study was designed to investigate the anti-inflammatory effects and molecular mechanisms of DNQ via alkylation of Keap1.DNQ exhibited signif-icant anti-inflammatory properties both in vitro and in vivo.The pharmacophore responsible for the anti-inflammatory properties of DNQ was determined to be the α,β-unsaturated amides moieties by a chemical reaction between DNQ and N-acetylcysteine.DNQ exerted anti-inflammatory effects through activation of Nrf2/ARE pathway.Keap1 was demonstrated to be the direct target of DNQ and bound with DNQ through conjugate addition reaction involving alkylation.The specific alkylation site of DNQ on Keap1 for Nrf2 activation was elucidated with a synthesized probe in conjunction with liquid chromatography-tandem mass spectrometry.DNQ triggered the ubiquitination and subsequent degra-dation of Keap1 by alkylation of the cysteine residue 489(Cys489)on Keap1-Kelch domain,ultimately enabling the activation of Nrf2.Our findings revealed that DNQ exhibited potent anti-inflammatory capacity through α,β-unsaturated amides moieties active group which specifically activated Nrf2 signal pathway via alkylation/ubiquitination of Keap1-Kelch domain,suggesting the potential values of targeting Cys489 on Keap1-Kelch domain by DNQ-like small molecules in inflammatory therapies.

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.

To investigate the effect of cantharidin ( CTD) on platelet function and the mechanism of anti-platelet aggregation. Methods Washed platelets were collected from the venous blood of healthy volunteers. The effect of CTD on platelet aggregation and release was determined by aggregometer. The CTD concentration was 2.5 ,5 ,10 μmol • L

Objective:To investigate the clinical efficacy of da Vinci Xi surgical system assisted laparoscopic exocytosis for hepatic echinococcosis.Methods:The retrospective and descriptive study was conducted. The clinicopathological data of 7 patients who underwent da Vinci Xi surgical system assisted laparoscopic exocytosis for hepatic echinococcosis in Xinjiang Uiger Municipal People′s Hospital from October 2019 to July 2021 were collected. There were 3 males and 4 females, aged (43±12)years. Observation indicators: (1) surgical situations; (2) complications; (3) follow-up. Mea-surement data with normal distribution were represented as Mean±SD, and measurement data with skewed distribution were represented as M(range). Count data were described as absolute numbers. Results:(1) Surgical situations. All 7 patients underwent da Vinci Xi surgical system assisted laparoscopic exocytosis for hepatic echinococcosis successfully, without conversion to laparotomy and laparoscopic surgery. None of the 7 patients underwent intraoperative blood transfusion and the operation time, volume of intraoperative blood loss, time to postoperative first and flatus, time to postoperative initial liquid food intake, time to postoperative abdominal drainage tube removal, time to postoperative urethral catheter removal, duration of postoperative hospital stay of 7 patients was (225±45)minutes, 100(range, 50-200)mL, (1.9±0.7)days, (4.2±1.2)days, (7±4)days, (2.9±0.8)days, (7±4)days, respectively. (2) Complications. None of the 7 patients had postoperative complications such as bile leakage, abdominal hemorrhage, incision infection, hydatid cavity infection, secondary operation, intestinal obstruction, pulmonary infection and deep venous thrombosis of lower limbs. (3) Follow-up. All 7 patients were followed up for 7 (range, 3-12) months. None of the 7 patients had recurrence of hepatic echinococcosis or peritoneal implantation and incision implantation, and all patients survived during follow-up.Conclusion:da Vinci Xi surgical system assisted laparoscopic exocytosis for hepatic echinococcosis is safe and feasible.

In the outbreak of COVID-19,triage procedures based on epidemiology were implemented in a local hospital in Changsha to control the transmission of SARS-CoV-2 and avoid healthcare-associated infection.This re-trospective study analyzed the data collected during the triage period and found that COVID-19 patients were en-riched 7 folds into the Section A designated for patients with obvious epidemiological history.On the other side,nearly triple amounts of visits were received at the Section B for patients without obvious epidemiological history.8 COVID-19 cases were spotted out of 247 suspected patients.More than 50％of the suspected patients were submi-tted to multiple rounds of nucleic acid analysis for SARS-CoV-2 infection.Of the 239 patients who were diagnosed as negative of the virus infection,188 were successfully revisited and none was reported as COVID-19 case.Of the 8 COVID-19 patients,3 were confirmed only after multiple rounds of nucleic acid analysis.Besides comorbidities,delayed sharing of epidemiological history added complexity to the diagnosis in practice.The triaging experience and strategy will be helpful for the control of infectious diseases in the future.

Chronic refractory wound (CRW) is one of the most challengeable issues in clinic due to complex pathogenesis, long course of disease and poor prognosis. Experts need to conduct systematic summary for the diagnosis and treatment of CRW due to complex pathogenesis and poor prognosis, and standard guidelines for the diagnosis and treatment of CRW should be created. The Guideline forthe diagnosis and treatment of chronic refractory wounds in orthopedic trauma patients ( version 2023) was created by the expert group organized by the Chinese Association of Orthopedic Surgeons, Chinese Orthopedic Association, Chinese Society of Traumatology, and Trauma Orthopedics and Multiple Traumatology Group of Emergency Resuscitation Committee of Chinese Medical Doctor Association after the clinical problems were chosen based on demand-driven principles and principles of evidence-based medicine. The guideline systematically elaborated CRW from aspects of the epidemiology, diagnosis, treatment, postoperative management, complication prevention and comorbidity management, and rehabilitation and health education, and 9 recommendations were finally proposed to provide a reliable clinical reference for the diagnosis and treatment of CRW.

Humans ; Transcatheter Aortic Valve Replacement ; Consensus ; Aortic Valve Stenosis/surgery* ; Aortic Valve/surgery* ; Reference Standards ; Treatment Outcome ; Heart Valve Prosthesis

AIM: To investigate long-term efficacy and safety of patients after excimer laser in situ keratomileusis(LASIK)surgery in 20a.METHODS: A retrospective study.Patients who underwent LASIK in our hospital from January 1998 to December 2001 were recruited. The patients were notified by telephone to the outpatient for follow-up. The collected data included demographic characteristics(gender and age), preoperative uncorrected distance visual acuity(UCVA)and best corrected visual acuity(BCVA), preoperative diopter, intraoperative corneal flap thickness and corneal stromal residual thickness(RST). The main indicators were long-term efficacy index, safety index, UCVA, BCVA, corneal thickness and axial length. The slit lamp, fundus and optical coherence tomography(OCT)examination were performed at the same time.RESULTS: A total of 95 patients(190 eyes)were recruited. At the final postoperative visit, there were 71 patients(142 eyes, 74.7%)had UCVA≥1.0, and 82 patients(164 eyes, 86.3%)had BCVA≥1.0. There were 2 eyes among them had bad BCVA(≤0.6)due to macular retinoschisis and glaucoma, respectively, while other patients' BCVA was 0.8. There was no significant correlation between the UCVA and BCVA of patients after surgery in 20a and the factors such as age at surgery, preoperative diopter and corneal thickness(P>0.05), but there was a negative correlation with the increase of axis length(rs=-0.32, -0.31, all P<0.05). UCVA and BCVA were positively correlated with corneal stromal residual thickness at the last postoperative follow-up(P<0.05). The safety and efficacy indexes of LASIK after surgery in 20a were 1.00±0.10 and 0.83±0.27, respectively. During the follow-up, no patients were found to have corneal ectasia and complications related to corneal flap, and no patients underwent secondary surgery. No patients with corneal dryness were found after silt lamp examination.CONCLUSION: LASIK after surgery in 20a shows good safety and efficacy.

Many people affected by fragile X syndrome (FXS) and autism spectrum disorders have sensory processing deficits, such as hypersensitivity to auditory, tactile, and visual stimuli. Like FXS in humans, loss of Fmr1 in rodents also cause sensory, behavioral, and cognitive deficits. However, the neural mechanisms underlying sensory impairment, especially vision impairment, remain unclear. It remains elusive whether the visual processing deficits originate from corrupted inputs, impaired perception in the primary sensory cortex, or altered integration in the higher cortex, and there is no effective treatment. In this study, we used a genetic knockout mouse model (Fmr1^KO), in vivo imaging, and behavioral measurements to show that the loss of Fmr1 impaired signal processing in the primary visual cortex (V1). Specifically, Fmr1^KO mice showed enhanced responses to low-intensity stimuli but normal responses to high-intensity stimuli. This abnormality was accompanied by enhancements in local network connectivity in V1 microcircuits and increased dendritic complexity of V1 neurons. These effects were ameliorated by the acute application of GABA_A receptor activators, which enhanced the activity of inhibitory neurons, or by reintroducing Fmr1 gene expression in knockout V1 neurons in both juvenile and young-adult mice. Overall, V1 plays an important role in the visual abnormalities of Fmr1^KO mice and it could be possible to rescue the sensory disturbances in developed FXS and autism patients.
Animals ; Disease Models, Animal ; Fragile X Mental Retardation Protein/metabolism* ; Fragile X Syndrome/metabolism* ; Humans ; Mice ; Mice, Knockout ; Neurons/metabolism*

Objective:To investigate the association between hepatic echinococcus granulosus infection and necrosis with gene polymorphism of interleukin-10 (IL-10) and tumor necrosis factor-α (TNF-α), and to identify the related factors at the gene level.Methods:A total of 106 patients with hepatic echinococcosis who underwent surgical treatment in the department of hepatobiliary surgery, People′s Hospital of Xinjiang Uygur Autonomous Region from January 2018 to December 2020 were selected. Patients with necrosis caused by hepatic echinococcus granulosus infection were selected as the observation group, and patients without necrosis caused by hepatic echinococcus granulosus infection were selected as the control group, with 53 cases in each group. The serum levels of IL-10 and TNF-α were detected by enzyme-linked immunosorbent assay (ELISA). The polymorphisms of IL-10 (-592, -1082) and TNF-α (rsl800630) were detected by polymerase chain reaction (PCR). The levels of IL-10 and TNF-α and their gene polymorphisms were analyzed.Results:The levels of serum IL-10 and TNF-α in the observation group were significantly higher than those in the control group (all P<0.05); There was significant difference in genotype and allele frequency of IL-10 (-592, -1082) and TNF-α (rsl800630) (all P<0.05). The serum IL-10 level of CC genotype patients with IL-10 gene -592C/A locus in the observation group was higher than that of CA+ AA genotype patients, with statistically significant difference ( P<0.05). The serum IL-10 level in patients with TT genotype at -1082T>A of IL-10 gene in the observation group was higher than that in patients with TA+ AA genotype, with statistically significant difference ( P<0.05). The serum TNF-α level in patients with CC genotype at rsl800630C/A locus of TNF-α gene in the observation group was higher than that in patients with CA+ AA genotype, with statistically significant difference ( P<0.05). Conclusions:The changes of IL-10 (-592, -1082) and TNF-α (rsl800630) gene polymorphisms may be associated with hepatic echinococcus granulosus infection and necrosis.