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.

A resurging interest in targeted covalent inhibitors (TCIs) focus on compounds capable of irreversibly reacting with nucleophilic amino acids in a druggable target. p97 is an emerging protein target for cancer therapy, viral infections and neurodegenerative diseases. Extensive efforts were devoted to the development of p97 inhibitors. The most promising inhibitor of p97 was in phase 1 clinical trials, but failed due to the off-target-induced toxicity, suggesting the selective inhibitors of p97 are highly needed. We report herein a new type of TCIs (i.e., FL-18) that showed proteome-wide selectivity towards p97. Equipped with a Michael acceptor and a basic imidazole, FL-18 showed potent inhibition towards U87MG tumor cells, and in proteome-wide profiling, selectively modified endogenous p97 as confirmed by in situ fluorescence scanning, label-free quantitative proteomics and functional validations. FL-18 selectively modified cysteine residues located within the D2 ATP site of p97. This covalent labeling of cysteine residue in p97 was verified by LC‒MS/MS-based site-mapping and site-directed mutagenesis. Further structure-activity relationship (SAR) studies with FL-18 analogs were established. Collectively, FL-18 is the first known small-molecule TCI capable of covalent engagement of p97 with proteome-wide selectivity, thus providing a promising scaffold for cancer therapy.

Child ; Humans ; Circulating Tumor DNA ; Lymphangioma ; Family ; Hemangioendothelioma ; Sarcoma, Kaposi

Objective:To investigate the role of TiRobot combined with O-arm assisted closed reduction and percutaneous screw fixation in unstable pelvic fracture surgery.Methods:Twelve patients with unstable pelvic fractures, 7 males and 5 females, aged 39.41±12.56 years (range 25-60 years), admitted from January 2020 to January 2021, were retrospectively analyzed. The duration between injury and surgery was 9.67±5.81 d (range 4-24 d). The following are the causes of injury, namely traffic injury in 6 cases, fall from height injury in 4 cases, crush injury in 2 cases. Tile type of pelvic fractures were 3 cases of type B (2 cases of type B2, 1 case of type B3), 9 cases of type C (4 cases of type C1, 3 cases of type C2, 2 cases of type C3). Sacral fractures with Denis division were 5 cases of zone I, 7 cases of zone II. Seven patients were repositioned by intraoperative traction on the injured side of the limb and maintained by fixation with a Starr frame. Two cases were repositioned by intraoperative longitudinal bone traction on each lower limb for fracture displacement. The other 3 B-type fractures were repositioned by inserting Schanz nails into the anterior inferior iliac spine bilaterally. Then, the fractures were maintained with external pelvic fixators. The fractures were assessed by O-arm fluoroscopy. Hollow screws were placed with the aid of orthopedic robotic guidance, and the screw positions were verified by O-arm fluoroscopy again after the nail placement. The duration of each screw placement and operation were recorded. The quality of fracture repositioning, hip function and postoperative complications were observed at the follow-up.Results:All patients were followed up for 8.17±1.99 months (range, 6-12 months). There were 27 screws inserted in 12 patients, with a single screw insertion duration of 19.9±1.8 min (range, 9-31 min). In all patients, one O-arm fluoroscopy was performed in each row after closed reduction and after completion of nail placement. The operative duration was 257.78±80.63 min (range, 160-450 min). The O-arm fluoroscopy after nail placement verified that 23 screws were placed in a satisfactory position at one time, with satisfactory rate of 85% (23/27) for the first nail placement. Two patients with preoperative grade II sacral plexus nerve injury recovered to grade I in one case and grade II in one case. However, the numbness was reduced after operation. No further aggravation of nerve injury occurred after surgery. The quality of fracture repositioning was evaluated according to the Matta score, including excellent in 9 cases, good in 2 cases, and acceptable in 1 case, with an excellent rate of 92% (11/12). At the last follow-up, the Majeed pelvic fracture quantitative assessment system scored 85.75±5.82 (range, 74-96). There were 8 cases in excellent and 4 cases in good. Twelve patients had one-stage wound healing. No complications, such as incision infection, nerve injury, loosening and breaking of the internal fixation occurred during the follow-up.Conclusion:TiRobot combined with O-arm assisted closed reduction and percutaneous screw fixation for unstable pelvic fractures has some advantages, including safety, precision, convenient nail placement, and less fluoroscopic radiation.

BACKGROUND: Hypertension is associated with stroke-related mortality. However, the long-term association of blood pressure (BP) and the risk of stroke-related mortality and the influence path of BP on stroke-related death remain unknown. The current study aimed to estimate the long-term causal associations between BP and stroke-related mortality and the potential mediating and moderated mediating model of the associations. METHODS: This is a 45-year follow-up cohort study and a total of 1696 subjects were enrolled in 1976 and 1081 participants died by the latest follow-up in 2020. COX proportional hazard model was used to explore the associations of stroke-related death with baseline systolic blood pressure (SBP)/diastolic blood pressure (DBP) categories and BP changes from 1976 to 1994. The mediating and moderated mediating effects were performed to detect the possible influencing path from BP to stroke-related deaths. E value was calculated in the sensitivity analysis. RESULTS: Among 1696 participants, the average age was 44.38 ± 6.10 years, and 1124 were men (66.3%). After a 45-year follow-up, a total of 201 (11.9%) stroke-related deaths occurred. After the adjustment, the COX proportional hazard model showed that among the participants with SBP ≥ 160 mmHg or DBP ≥ 100 mmHg in 1976, the risk of stroke-related death increased by 217.5% (hazard ratio [HR] = 3.175, 95% confidence interval [CI]: 2.297-4.388), and the adjusted HRs were higher in male participants. Among the participants with hypertension in 1976 and 1994, the risk of stroke-related death increased by 110.4% (HR = 2.104, 95% CI: 1.632-2.713), and the adjusted HRs of the BP changes were higher in male participants. Body mass index (BMI) significantly mediated the association of SBP and stroke-related deaths and this mediating effect was moderated by gender. CONCLUSIONS In a 45-year follow-up, high BP and persistent hypertension are associated with stroke-related death, and these associations were even more pronounced in male participants. The paths of association are mediated by BMI and moderated by gender.
Adult ; Blood Pressure/physiology* ; China/epidemiology* ; Follow-Up Studies ; Humans ; Hypertension ; Male ; Middle Aged ; Risk Factors ; Stroke

Sterols, a class of cyclopentane poly-hydrophenanthrene derivatives, are the predominant membrane constituent of eukaryotes. These substances have a variety of biological activities and have been widely used in food and pharmaceutical industries. The presence of endogenous ergosterol biosynthetic pathway in Saccharomyces cerevisiae cells make it an ideal chassis for the de novo synthesis of sterol and its derivatives. Most recently, the rational modification of organelles provides a novel strategy for the directed transportation and storage of target products and the ultimate enhanced product synthesis. This review summarizes the phenotypic responses of S. cerevisiae cells upon different physiological stimulations and the underlying molecular mechanisms. Reinforcement of sterol production through directed storage, transportation, and excretion of sterols offers a novel strategy for breaking the limitation of de novo biosynthesis of sterols in yeast.
Ergosterol ; Phytosterols ; Saccharomyces cerevisiae ; Sterols

Objective To evaluate the efficacy of tigecycline plus prolonged high-dose meropenem infusion in the prevention and treatment of early carbapenem-resistant Klebsiella pneumoniae (CRKP) infection after renal transplantation .Methods From January 2016 to December 2018 ,clinical data were retrospectively analyzed for 13 renal transplant recipients with graft-carried CRKP .The relevant clinical data included treatments and outcomes of grafts and recipients .KPC-2 gene was the only resistance gene detectable in all isolates of CRKP . Among 13 CRKP positive recipients ,there were positive cultures of graft preservation solution ,recipient blood & urine (n=1) , positive cultures of graft preservation solution & urine (n=1) ,positive cultures of graft preservation solutions & peri-graft drainage (n=3) ,continuous positive cultures of peri-graft drainage more than twice (n= 3) and positive culture of graft preservation solution (n= 5).All patients received tigecycline plus prolonged high-dose meropenem infusion-based antibiotics .Results Five patients with CRKP positive in preservation solution were successfully prevented from infection after a treatment period of (12 .4 ± 2 .1)days .Among another 8 cases ,additional topical medications (n= 3) and surgical debridement (n= 1) were used .It took a median time of 16 (7～60) days until a negative culture and the total antibiotic treatment course was 20 (10～93) days .The average hospitalization duration was (50 ± 35) days .During a median follow-up period of 25 (6～28) months ,there was no onset of renal arterial rupture ,graft nephrectomy or death .The survival rate was 100％ for recipients and 92 .3％ for grafts .Conclusions For post-transplant infections due to graft-carried KPC-2 producing CRKP ,rapid diagnostics and tigecycline plus prolonged high-dose meropenem infusion may optimize clinical outcomes by decreasing the rate of graft nephrectomy and the recipient mortality .

Objective: To observe the effects of the method of combining free superficial temporal fascia flaps with skin grafts in repairing deep wounds in posterior ankle region of extensively burned patients. Methods: From September 2013 to February 2017, 11 extensively burned patients with deep tissue defects in posterior ankle region were treated in our unit. Two patients had tissue defects in bilateral posterior ankle regions. The wound sizes ranged from 5.8 cm×4.6 cm to 11.7 cm×5.2 cm. Free superficial temporal fascia flaps with the same sizes as the wounds were designed and resected to repair wounds in posterior ankle regions after debridement. The proximal end of superficial temporal veins and posterior tibial veins were performed with end-to-end anastomosis, and superficial temporal arteries and posterior tibial arteries were performed with end-to-side anastomosis. Skin grafts were resected to cover the superficial temporal fascia flaps according to patients′ condition of donor sites. The donor sites were sutured directly. Results: All fascial flaps in 11 patients survived, while 2 skin grafts had partial necrosis, and they healed after secondary skin graft. All patients were followed up for 6 to 13 months, and the shape and function of the operation sites in all patients recovered well. Conclusions The method of combining free superficial temporal fascia flaps with skin grafts can repair deep wounds in posterior ankle regions of extensively burned patients. It has the advantages of good appearances in the recipient sites, strong resistances to infection of fascia flaps, minimal damages to the donor sites, short course of disease, and good prognosis of patients.

Objective To determine the impact and the risk factors of different methods of preoperative biliary drainage (PBD) for malignant obstruction jaundice (MOJ) on overall survival (OS).Methods Databases including the PubMed,Medline,Web of Knowledge,and other databases were searched up to 30th April,2018 for clinical studies which compared the OS rates between percutaneous transhepatic biliary drainage (PTBD) and endoscopic biliary drainage (EBD) for MOJ.Hazard ratio (HR) and Odds Ratio (OR) with 95％ confidence interval (CI) were performed using the Review Manager 5.3 software to synthesize the results.Results Nine studies were enrolled in this meta-analysis,which included 818 patients in the PTBD group and 1253 patients in the EBD group.EBD was shown to be superior to PTBD in OS (HR=0.63,95％ CI:0.51～0.77,P＜0.05).Risk factors analysis showed that patients in the EBD group had a higher rate of early tumor stage (P＜0.05) and a lower rate of lymphatic metastasis (P＜0.05).When compared with the PTBD group,the EBD group had a lower rate of intraoperative bleeding (P＜0.05),and a higher rate of adjuvant therapy (P＜0.05).Conclusion In PBD for patients with resectable MOJ,there was insufficient evidence to support EBD to be superior to PTBD in OS.

Objective To compare the short-term safety and efficacy of radiofrequency ablation (RFA) and microwave ablation (MWA) for treatment of large benign thyroid nodules.Methods A total of 34 patients with large benign thyroid nodules were studied retrospectively,including 13 patients treated with ultrasound-guided RFA and 21 patients treated with MWA between Jun.,2016 and Feb.,2017 in Zhongshan Hospital.The thyroid function parameters,serum antibodies,complications and thyroid nodules volume reduction rate(VRR) were compared between the two groups during the follow-up.Results There were no statistically significant differences(P＞0.05)among those patients before and after treatment in serum free triiodothyronine (fT3),free thyroxine (fT4),thyroid stimulating hormone (TSH),anti-thyroglobulin antibodies (TG-Ab) levels,and thyroid peroxidase antibodies (TPO-Ab).One patient in the MWA group had mild hoarseness after ablation and another patient in the RFA group had intraoperative hemorrhage for about 10 mL.There were no other complications such as neck scar,postoperative infection,skin burns,tracheal and esophageal injury.One day after the ablation,all nodules were showed hypoecho and contrast-enhanced ultrasound proved there was no blood supply.One month after treatment,no statistically significant difference was found in VRR between two groups (23.8％ vs.22.6％,P =0.127).Conclusions RFA and MWA are safe and effective treatments for large benign thyroid nodules,and no significant difference was observed in short-term follow-up.