PURPOSE: To compare the effects of empirical and modified hemostatic resuscitation for liver blast injury combined with seawater immersion. METHODS: Thirty rabbits were subjected to liver blast injury combined with seawater immersion, and were then divided into 3 groups randomly (n = 10 each): group A (no treatment after immersion), group B (empirical resuscitation with 20 mL hydroxyethyl starch, 50 mg tranexamic acid, 25 IU prothrombin complex concentrate and 50 mg/kg body weight fibrinogen concentrate), and group C (modified resuscitation with additional 10 IU prothrombin complex concentrate and 20 mg/kg body weight fibrinogen concentrate based on group B). Blood samples were gathered at specified moments for assessment of thromboelastography, routine coagulation test, and biochemistry. Mean arterial pressure, heart rate, and survival rate were also documented at each time point. The Kolmogorov-Smirnov test was used to examine the normality of data distribution. Multigroup comparisons were conducted with one-way ANOVA. RESULTS: Liver blast injury combined with seawater immersion resulted in severe coagulo-fibrinolytic derangement as indicated by prolonged prothrombin time (s) (11.53 ± 0.98 vs. 7.61 ± 0.28, p＜0.001), activated partial thromboplastin time (APTT) (s) (33.48 ± 6.66 vs. 18.23 ± 0.89, p＜0.001), reaction time (R) (min) (5.85 ± 0.96 vs. 2.47 ± 0.53, p＜0.001), decreased maximum amplitude (MA) (mm) (53.20 ± 5.99 vs. 74.92 ± 5.76, p＜0.001) and fibrinogen concentration (g/L) (1.19 ± 0.29 vs. 1.89 ± 0.32, p = 0.003), and increased D-dimer concentration (mg/L) (0.38 ± 0.32 vs. 0.05 ± 0.03, p = 0.005). Both empirical and modified hemostatic resuscitation could improve the coagulo-fibrinolytic states and organ function, as indicated by shortened APTT and R values, decreased D-dimer concentration, increased fibrinogen concentration and MA values, lower concentration of blood urea nitrogen and creatine kinase-MB in group B and group C rabbits in comparison to that observed in group A. Further analysis found that the R values (min) (4.67 ± 0.84 vs. 3.66 ± 0.98, p = 0.038), APTT (s) (23.16 ± 2.75 vs. 18.94 ± 1.05, p = 0.001), MA (mm) (60.10 ± 4.74 vs. 70.21 ± 3.01, p < 0.001), and fibrinogen concentration (g/L) (1.68 ± 0.21 vs. 1.94 ± 0.16, p = 0.013) were remarkably improved in group C than in group B at 2 h and 4 h after injury. In addition, the concentration of blood urea nitrogen (mmol/L) (24.11 ± 1.96 vs. 21.00 ± 3.78, p = 0.047) and creatine kinase-MB (U/L) (85.50 ± 13.60 vs. 69.74 ± 8.56, p = 0.013) were lower in group C than in group B at 6 h after injury. The survival rates in group B and group C were significantly higher than those in group A at 4 h and 6 h after injury (p < 0.001), however, there were no statistical differences in survival rates between group B and group C at each time point. CONCLUSIONS Modified hemostatic resuscitation could improve the coagulation parameters and organ function better than empirical hemostatic resuscitation.
Animals ; Rabbits ; Resuscitation/methods* ; Liver/injuries* ; Seawater ; Blast Injuries/therapy* ; Fibrinogen/administration & dosage* ; Male ; Tranexamic Acid/administration & dosage* ; Immersion ; Hydroxyethyl Starch Derivatives/administration & dosage*

Objective To evaluate the resuscitation efficacy of novel lyophilized platelets(LP,thrombin-stimulated platelets)combined with lactated Ringer's(LR)solution in rabbits with hemorrhagic shock and seawater immersion.Methods Fifty rabbits were randomly assigned to 5 groups(Groups A,B,C,D and E,n=10).After all rabbits were anesthetized with 3%pentobarbital sodium at a dose of 1 mL/kg,soft tissue injury was inflicted in the left lower limb.The blood loss from the soft tissue injury was quantified after gauze hemostasis.The right lower limb was subjected to femoral artery catheterization,followed by blood withdrawal equivalent to 26%of the total blood volume of the rabbit.The rabbits were then vertically immersed in 3%artificial seawater,with the water level reaching above the xiphoid process,and were retrieved in 15 min later.Resuscitation strategies were applied to the rabbits from different group:Group A(no resuscitation),Group B(resuscitation with LR solution),Group C(resuscitation with LR solution and fresh platelets),Group D(resuscitation with LR solution and LP),and Group E(resuscitation with LR solution and novel LP).Coagulation function test,routine blood test,blood gas analysis,and thromboelastography were conducted at baseline and at 1,2 and 4 h after injury.Results The LP and rabbit model of hemorrhagic shock and seawater immersion were successfully prepared.At 1 h after injury,the mean arterial pressure(MAP)of Groups C,D and E(infused with platelet preparations)was significantly higher than that of Group A(without resuscitation,P<0.05);the lactate(Lac)content of Group C was obviously lower than that of Groups A and B(P<0.05);the base excess(BE)and blood urea nitrogen(BUN)levels of Groups C,D and E were notably lower than those of Groups A and B(P<0.05);and the prothrombin time(PT)of Group A was significantly longer than that of before injury(P<0.05).At 2 h after injury,the MAP of Groups C and D was significantly higher than that of Groups A and B,and that of Group E was notably higher than that of Group A(P<0.05);the Lac content of Groups C and E was obviously lower than that of Groups A and B,while that of Group D was also lower than that of Group A(P<0.05);the BE and BUN levels of Groups C,D and E were remarkably lower than those of Groups A and B(P<0.05);the maximum amplitude(MA)value of Group C was higher than that of Group A,while the value of Groups A and D at this time was significantly lower than the corresponding value before injury(P<0.05);and the activated partial clotting time(APTT)of Groups A and D was statistically longer than the corresponding baseline time(P<0.05).At 4 h after injury,the MAP of Groups C,D,and E was higher than that of Groups A and B,and that of Group B was higher than that of Group A(P<0.05);the Lac and BUN levels of Groups C,D,and E were lower than those of Groups A and B(P<0.05);the BE level of Groups C and D were lower than those of Groups A and B(P<0.05);the MA value of Groups B,C,and E were higher than those of Group A(P<0.05),while the MA value and APTT value of Groups A and D were significantly lower than their corresponding baseline values(P<0.05).Conclusion For rabbits with hemorrhagic shock and seawater immersion,the novel LP combined with LR solution can significantly increase the MAP level,reduce Lac content,and sustainably maintain blood clot firmness and coagulation function.

Objective:To identify predictors of adverse pregnancy outcomes(APOs)in patients with systemic lupus erythematosus(SLE).Methods:A retrospective analysis was conducted on 318 SLE pa-tients who delivered at Peking University People's Hospital from May 2016 to September 2021.These pa-tients were categorized into two groups:The APOs group(n=85)and the non-APOs group(n=233).Various factors,including disease duration,clinical manifestations,laboratory parameters,and systemic lupus erythematosus disease activity index 2000(SLED AI-2000)scores,were analyzed for their associa-tion with APOs.SPSS 26.0 software was used to analyze the data.Results:The mean age of SLE pa-tients in this study was(24.65±5.26)years.Among the 318 pregnancies studied,302(302/318,94.97％)resulted in live births,while 16(16/318,5.03％)cases ended in stillbirths,with no neonatal deaths reported.Among the live births,206(206/302,68.21％)were full-term infants,65(65/302,21.52％)cases were small for gestational age(SGA),and 31(31/302,10.26％)cases were preterm.The SLEDAI-2000 scores were significantly higher in the APOs group compared with the non-APOs group(5.82±4.97 vs.3.74±3.72,t=4.019,P=0.001),suggesting greater disease activity as a risk fac-tor.Similarly,glucocorticoid doses were markedly higher in the APOs group[12.50(7.50,50.00)mg vs.10.00(5.00,15.00)mg,P＜0.001],underscoring the link between disease severity and APOs.Univariate analysis revealed that lupus nephritis(31.76％vs.21.03％,x2=3.946,P=0.047),throm-bocytopenia(24.71％vs.9.01％,x2=13.380,P＜0.001),hypocomplementemia(36.47％vs.26.03％,x2=4.847,P=0.028),antiphospholipid antibody positivity(20.00％vs.11.16％,x2=4.163,P=0.041),and absence of pregnancy treatment(21.18％vs.11.59％,x2=4.713,P=0.030)were associated with increased APOs risk.Multivariate Logistic regression identified thrombocyto-penia(OR=2.671,95％CI:1.309-5.449,P=0.007),hypocomplementemia(OR=1.935,95％CI:1.104-3.393,P=0.021),and antiphospholipid antibody positivity(OR=2.153,95％CI:1.054-4.399,P=0.035)as independent predictors of APOs.Conclusion:These findings highlight that certain clinical and laboratory features,including thrombocytopenia,hypocomplementemia,and antiphospholipid antibody positivity,are critical independent predictors of APOs in SLE patients.The study underscores the importance of close monitoring and proactive management of these risk factors to improve pregnancy outcomes in SLE patients.

Objective:To investigate the clinical data, drug resistance and treatment prognosis of Cryptococcus neoformans isolated from patients with acquired immunodeficiency syndrome(AIDS) in a hospital in Shanghai. Methods:The clinical data of AIDS patients with Cryptococcus neoformans infection in Shanghai Public Health Clinical Center from January 2014 to December 2023, and the drug sensitivity to 5 antifungal drugs in vitro, treatment and prognosis were retrospectively analyzed. Results:From January 2014 to December 2023, there were 295 AIDS patients with Cryptococcus neoformans infection in our hospital, with 255 males and 40 females. CD4 + T lymphocyte counts ≤100 cells/μl were detected in 251 patients. A total of 384 strains of Cryptococcus neoformans were isolated from the 295 patients, with the highest detection rate in cerebrospinal fluid samples (65.9%, 253/384), followed by blood samples (29.4%, 113/384). The sensitivity of 384 strains of Cryptococcus neoformans to 5-fluorocytosine was the highest (98.5%, 379/384), followed by fluconazole (95.6%, 367/384) and amphotericin B (95.3%, 366/384). After treatment against cryptococcal infection, 252 patients (86.0%, 252/293) were discharged and 20 patients (6.8%, 20/293) died. The other 2 cases were not treated for cryptococcal infection. Conclusions:As Cryptococcus neoformans is an important pathogen of AIDS patients, clinicians should actively carry out laboratory examination of Cryptococcus and rational drug use according to the results of drug sensitivity test, while alert to the occurrence of drug resistance.

Objective:To identify predictors of adverse pregnancy outcomes(APOs)in patients with systemic lupus erythematosus(SLE).Methods:A retrospective analysis was conducted on 318 SLE pa-tients who delivered at Peking University People's Hospital from May 2016 to September 2021.These pa-tients were categorized into two groups:The APOs group(n=85)and the non-APOs group(n=233).Various factors,including disease duration,clinical manifestations,laboratory parameters,and systemic lupus erythematosus disease activity index 2000(SLED AI-2000)scores,were analyzed for their associa-tion with APOs.SPSS 26.0 software was used to analyze the data.Results:The mean age of SLE pa-tients in this study was(24.65±5.26)years.Among the 318 pregnancies studied,302(302/318,94.97％)resulted in live births,while 16(16/318,5.03％)cases ended in stillbirths,with no neonatal deaths reported.Among the live births,206(206/302,68.21％)were full-term infants,65(65/302,21.52％)cases were small for gestational age(SGA),and 31(31/302,10.26％)cases were preterm.The SLEDAI-2000 scores were significantly higher in the APOs group compared with the non-APOs group(5.82±4.97 vs.3.74±3.72,t=4.019,P=0.001),suggesting greater disease activity as a risk fac-tor.Similarly,glucocorticoid doses were markedly higher in the APOs group[12.50(7.50,50.00)mg vs.10.00(5.00,15.00)mg,P＜0.001],underscoring the link between disease severity and APOs.Univariate analysis revealed that lupus nephritis(31.76％vs.21.03％,x2=3.946,P=0.047),throm-bocytopenia(24.71％vs.9.01％,x2=13.380,P＜0.001),hypocomplementemia(36.47％vs.26.03％,x2=4.847,P=0.028),antiphospholipid antibody positivity(20.00％vs.11.16％,x2=4.163,P=0.041),and absence of pregnancy treatment(21.18％vs.11.59％,x2=4.713,P=0.030)were associated with increased APOs risk.Multivariate Logistic regression identified thrombocyto-penia(OR=2.671,95％CI:1.309-5.449,P=0.007),hypocomplementemia(OR=1.935,95％CI:1.104-3.393,P=0.021),and antiphospholipid antibody positivity(OR=2.153,95％CI:1.054-4.399,P=0.035)as independent predictors of APOs.Conclusion:These findings highlight that certain clinical and laboratory features,including thrombocytopenia,hypocomplementemia,and antiphospholipid antibody positivity,are critical independent predictors of APOs in SLE patients.The study underscores the importance of close monitoring and proactive management of these risk factors to improve pregnancy outcomes in SLE patients.

Objective:To investigate the clinical data, drug resistance and treatment prognosis of Cryptococcus neoformans isolated from patients with acquired immunodeficiency syndrome(AIDS) in a hospital in Shanghai. Methods:The clinical data of AIDS patients with Cryptococcus neoformans infection in Shanghai Public Health Clinical Center from January 2014 to December 2023, and the drug sensitivity to 5 antifungal drugs in vitro, treatment and prognosis were retrospectively analyzed. Results:From January 2014 to December 2023, there were 295 AIDS patients with Cryptococcus neoformans infection in our hospital, with 255 males and 40 females. CD4 + T lymphocyte counts ≤100 cells/μl were detected in 251 patients. A total of 384 strains of Cryptococcus neoformans were isolated from the 295 patients, with the highest detection rate in cerebrospinal fluid samples (65.9%, 253/384), followed by blood samples (29.4%, 113/384). The sensitivity of 384 strains of Cryptococcus neoformans to 5-fluorocytosine was the highest (98.5%, 379/384), followed by fluconazole (95.6%, 367/384) and amphotericin B (95.3%, 366/384). After treatment against cryptococcal infection, 252 patients (86.0%, 252/293) were discharged and 20 patients (6.8%, 20/293) died. The other 2 cases were not treated for cryptococcal infection. Conclusions:As Cryptococcus neoformans is an important pathogen of AIDS patients, clinicians should actively carry out laboratory examination of Cryptococcus and rational drug use according to the results of drug sensitivity test, while alert to the occurrence of drug resistance.

Objective:To establish a practical and systematic pre-deployment base-based training course for medical units in peacekeeping level-II hospitals.Methods:We surveyed the current status of pre-deployment training of medical teams in peacekeeping level-II hospitals, and organized expert discussions to preliminarily construct centralized training course contents. At the same time, the Delphi method was used to conduct two rounds of questionnaire-based consultation to evaluate the overall framework design of the course and the rationality and importance scores of each module. The contents of the pre-deployment training course were further selected and optimized based on the positive coefficient (%), authority coefficient (Cr), coefficient of concordance ( W), and coefficient of variation (Cv). Results:The contents of the pre-deployment training course for the medical units of peacekeeping level-II hospitals were preliminarily established. The experts scored high for the combat onsite first-aid skills module [rationality score, (9.32±0.75) points; importance score, (9.45±0.65) points] and the combat wound treatment module [rationality score, (9.33±0.75) points; importance score, (9.28±0.74) points], and scored lowest for the field survival module [rationality score, (7.95±2.28) points; importance score, (7.87±2.16) points].Conclusions:The established contents of the pre-deployment base-based training course for the medical units of peacekeeping level-II hospitals are reasonable and practical, which lays the foundation for perfecting the pre-deployment training system of peacekeeping medical teams.

Objectives:To assess the clinical characteristics and lead extraction in patients with venous occlusion related to infection of cardiovascular implantable electronic devices. Methods:Clinical data of 405 patients(147 men,mean age[62.4±13.2]years)who underwent lead extraction from January 2020 to January 2024 in Peking University People's Hospital were reviewed.Contrast venography of the access vein was retrospectively analyzed.The patients were divided into venous occlusion group(n=119)and non-venous occlusion group(n=286)according to the presence or absence of venous occlusion.The clinical characteristics and lead extraction of patients in two groups were analyzed. Results:Occlusion of the access vein occurred in 119 patients(29.4%).The subclavian vein was occluded in 48 cases(40.3%),brachiocephalic vein was occluded in 37 cases(31.1%),axillary vein was occluded in 30 cases(25.2%),superior vena cava was occluded in 4 cases(3.4%).There were no significant differences between venous occlusion group and non-venous occlusion group in terms of age,sex,device type,number of leads,or anticoagulation therapy(all P>0.05).Time from implant of the initial leads was significantly longer in the venous occlusion group than in the non-venous occlusion group([10.4±3.8]years vs.[5.9±4.1]years,P=0.042).Clinical extraction success rate and complications were similar between the venous occlusion group and the non-venous occlusion group(both P>0.05).Procedural duration and fluoroscopy exposure time were significantly lower in non-venous occlusion group than in the venous occlusion group(both P<0.05).Patients in the venous occlusion group required more advanced tools(such as laser sheaths,evolution sheaths,and needle's eye snares)for lead extraction compared to patients in the non-venous occlusion group(84.0%vs.67.1%,P=0.001). Conclusions:The incidence of venous occlusion related to infection of cardiovascular implantable electronic devices is 29.4%.Time from implant of the initial leads is significantly longer and lead extraction is more difficult in patients with venous occlusion,and requires more advanced tools and more time to achieve the successful lead extraction.

The clustered regularly interspaced short palindromic repeats (CRISPR)-Cas9 system has been widely used for genome engineering and transcriptional regulation in many different organisms. Current CRISPR-activation (CRISPRa) platforms often require multiple components because of inefficient transcriptional activation. Here, we fused different phase-separation proteins to dCas9-VPR (dCas9-VP64-P65-RTA) and observed robust increases in transcriptional activation efficiency. Notably, human NUP98 (nucleoporin 98) and FUS (fused in sarcoma) IDR domains were best at enhancing dCas9-VPR activity, with dCas9-VPR-FUS IDR (VPRF) outperforming the other CRISPRa systems tested in this study in both activation efficiency and system simplicity. dCas9-VPRF overcomes the target strand bias and widens gRNA designing windows without affecting the off-target effect of dCas9-VPR. These findings demonstrate the feasibility of using phase-separation proteins to assist in the regulation of gene expression and support the broad appeal of the dCas9-VPRF system in basic and clinical applications.
Humans ; Transcriptional Activation ; RNA, Guide, CRISPR-Cas Systems ; Gene Expression Regulation ; CRISPR-Cas Systems/genetics*

Objective:To investigate the characteristics of the sleep quality and health-related quality of life (HRQoL), and analyze the different effects of sleep quality on HRQoL among young and middle-aged people.Methods:A cross-sectional study recruited 1 976 participants.All participants completed a self-designed questionnaire for the adults' general condition, the Pittsburgh sleep quality index (PSQI) and Short-Form health survey (SF-36). All participants were divided into 3 age groups: 18-29-year-old group( n=1 148), 30-44-year-old group( n=586) and 45-59-year-old group ( n=242). SPSS 23.0 software was used for statistical analysis.Chi-square test was used to analyze the general characteristics of the three age groups.Non-parametric test was used to analyze the scores of the three age groups in different dimensions of sleep quality. One-way ANOVA was used to analyze the mean scores of the three age groups in different dimensions of HRQoL. Stepwise regression analysis was used to analyze the effect of sleep quality on HRQoL among the three groups after control the confounding factors such as marital status, education, smoking, drinking and exercise habits and past medical history. Results:In terms of sleep quality, the total PSQI scores of 18-29-year-old, 30-44-year-old and 45-59-year-old groups(4(2, 6), 4(2, 6), 4(2, 6)) showed statistically significant differences ( Z=10.951, P=0.004). In terms of HRQoL, there were statistically significant differences in physical component summary scores (18-29-year-old: 82.51±12.62, 30-44-year-old: 80.72±13.63, 45-59-year-old: 82.04±13.07, F=3.667, P=0.026) and mental component summary scores(18-29-year-old: 76.09±15.46, 30-44-year-old: 77.20±16.14, 45-59-year-old: 81.82±14.14, F=13.649, P<0.001) among young and middle-aged people in different age groups.Regression analysis found that daytime dysfunction was an independent influencing factor for HRQoL in young and middle-aged population ( β=-0.308--0.425, all P<0.01). Sleep disorders significantly decreased Physical Component Summary of HRQoL in young-aged people ( β=-0.127--0.215, all P<0.01). The use of hypnotic drugs significantly reduced the scores in the physiological field in the young adults aged 30-44 ( β=-0.076, P<0.05). The duration of sleep significantly decreased the scores in the mental domain of young adults aged 30-44 ( β=-0.112, P<0.01). Subjective sleep quality was an independent factor that significantly decreased HRQoL in young adults aged 18-29 and 30-44 years ( β=-0.089--0.169, all P<0.01). Conclusion:Sleep quality and HRQoL of young and middle-aged people in different age groups show different characteristics.The effect of sleep quality on HRQoL is different among people in different ages.Taking targeted interventions for people of different ages to improve the sleep quality may be an effective way to improve their HRQoL.