Objective To explore the application efficacy and safety of oblique ultrasound-guided techniques in PICC puncture,in order to provide guidance and references for clinical application.Methods Through convenient sampling,654 patients from a tertiary A hospital in Zhejiang Province from March to December 2022 were selected as the study subjects.The random numbers were generated through Excel table functions and they were randomly grouped into 3 groups:A,B,and C.The ultrasound short axis method,long axis method,and oblique axis method were employed to guide PICC puncture catheterization,respectively.The success rate of PICC puncture,the number of subcutaneous adjustments of the puncture needle,puncture time,and the occurrence of puncture complications(such as hematoma,puncture of the posterior wall of blood vessels,accidental injury to arteries,and accidental injury to nerves)were recorded during the catheterization process in 3 groups.Results A total of 654 patients completed the study,including 215 in group A,219 in group B,and 220 in group C.The success rate of first-time puncture in the group C(86.36％)was higher than that in group A(73.95％)and group B(63.93％),and there was a statistically significant difference among 3 groups(P＜0.001).The subcutaneous adjustment frequency of the puncture needle was 1(1,1)in group C,1(1,2)in group A,and 1(1,2)in group B.The difference between 3 groups was statistically significant(P＜0.001);the puncture time of group C was shorter than that of group A and group B,and the difference was statistically significant(P＜0.001).There was a statistically significant difference in the puncture time between 3 groups(P＜0.017);the pairwise comparison of the number of subcutaneous needle adjustments and the success rate of a puncture between 3 groups showed that there was a statistical difference between group C and group A,and between group C and group B(P＜0.017),while there was no statistical difference between group A and group B(P＞0.017).There was statistical significance(P＜0.05)among 3 groups in terms of complications such as accidental nerve injury and puncture of the contralateral vascular wall by puncture needle,but there was no statistical significance in terms of accidental arterial injury and hematoma occurrence among 3 groups.Conclusion Compared with the short axis approach and the long axis approach,the ultrasound oblique axis approach guided PICC puncture has statistical differences in the success rate of a puncture and the incidence of puncture complications,etc.It is recommended to use the ultrasound oblique axis approach during PICC puncture.

Objective To investigate the effects and molecular mechanisms of inhibition of the Ras homolog gene(Rho)/Rho-associated coiled-coil forming protein kinase(ROCK)pathway on the proliferation and migration of airway smooth muscle cells involving myocardin(MYOCD).Methods Human airway smooth muscle cells were infected with the adenoviral vector Ad-ZsGreen-shRNA-hROCK1 in vitro.The cells were randomly divided into four groups:ROCK1 gene silencing control(shNC)group,shNC+arachidonic acid(AA,Rho/ROCK pathway activator)group,ROCK1 gene silencing(shROCK1)group,and shROCK1+AA group(n=3 each).Quantitative real-time polymerase chain reaction and Western blot were used to detect the expression levels of ROCK1 and MYOCD mRNA and protein.ELISA was employed to measure the levels of globular actin and filamentous actin,while immunofluorescent staining and scratch assays were utilized to assess cell proliferation and migration.Results Compared to the shNC+AA group,the shROCK1+AA group exhibited decreased levels of ROCK1 and MYOCD mRNA and protein expression,reduced expression levels of globular actin and filamentous actin,and diminished cell proliferation and migration capabilities(P<0.05).Conclusions Inhibition of the Rho/ROCK pathway suppresses the proliferation and migration of airway smooth muscle cells,which may be associated with the downregulation of MYOCD.

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.

OBJECTIVES: To investigate the correlation of serum levels of bridging integrating factor 1 (BIN1) with acute myocardial infarction (AMI) and Killip class of the patients. METHODS: We retrospectively collected the data from 94 patients with AMI and 30 healthy individuals for analysis of the correlations of serum BIN1 levels with Killip class, TIMI scores, and neutrophil-to-lymphocyte ratio (NLR). We also assessed the diagnostic value of BIN1 combined with NLR for AMI. RESULTS: Serum BIN1 levels were significantly lower in AMI patients than in the healthy individuals (P=0.032). The AMI patients with Killip class I had significantly lower serum BIN1 levels than the healthy individuals (P=0.008). Serum BIN1 level was an independent predictor of AMI with a predictive value of 0.630 (95% CI: 0.513-0.748) at the optimal cutoff level of 0.341 ng/mL, a specificity of 50%, and a sensitivity of 78.5%. Serum BIN1 level was also an independent predictor for Killip class I group in the AMI patients with a predictive value of 0.672 (95% CI: 0.548-0.797) at the optimal cutoff level of 0.287 ng/mL, a specificity of 74.1%, and a sensitivity of 60%. For AMI diagnosis, the combination of NLR and serum BIN1 level had a predictive value of 0.811 (95% CI: 0.727-0.895) at the optimal cutoff level of 0.548 ng/mL, with a specificity of 92.6% and a sensitivity of 62.2%. There was a positive correlation between serum BIN1 level and TIMI score in AMI patients (r=0.186, P=0.003). CONCLUSIONS BIN1 is correlated with AMI and can be helpful for predicting short-term prognosis of the patients, and BIN1 combined with NLR has a high diagnostic value for AMI.
Humans ; Myocardial Infarction/diagnosis* ; Tumor Suppressor Proteins/blood* ; Adaptor Proteins, Signal Transducing/blood* ; Retrospective Studies ; Nuclear Proteins/blood* ; Lymphocytes/cytology* ; Neutrophils/cytology* ; Female ; Male ; Prognosis ; Middle Aged

Objective:To investigate the diagnostic accuracy of serological indicators and evaluate the diagnostic value of a new established combined serological model on identifying the minimal hepatic encephalopathy (MHE) in patients with compensated cirrhosis.Methods:This prospective multicenter study enrolled 263 compensated cirrhotic patients from 23 hospitals in 15 provinces, autonomous regions and municipalities of China between October 2021 and August 2022. Clinical data and laboratory test results were collected, and the model for end-stage liver disease (MELD) score was calculated. Ammonia level was corrected to the upper limit of normal (AMM-ULN) by the baseline blood ammonia measurements/upper limit of the normal reference value. MHE was diagnosed by combined abnormal number connection test-A and abnormal digit symbol test as suggested by Guidelines on the management of hepatic encephalopathy in cirrhosis. The patients were randomly divided (7∶3) into training set ( n=185) and validation set ( n=78) based on caret package of R language. Logistic regression was used to establish a combined model of MHE diagnosis. The diagnostic performance was evaluated by the area under the curve (AUC) of receiver operating characteristic curve, Hosmer-Lemeshow test and calibration curve. The internal verification was carried out by the Bootstrap method ( n=200). AUC comparisons were achieved using the Delong test. Results:In the training set, prevalence of MHE was 37.8% (70/185). There were statistically significant differences in AMM-ULN, albumin, platelet, alkaline phosphatase, international normalized ratio, MELD score and education between non-MHE group and MHE group (all P<0.05). Multivariate Logistic regression analysis showed that AMM-ULN [odds ratio ( OR)=1.78, 95% confidence interval ( CI) 1.05-3.14, P=0.038] and MELD score ( OR=1.11, 95% CI 1.04-1.20, P=0.002) were independent risk factors for MHE, and the AUC for predicting MHE were 0.663, 0.625, respectively. Compared with the use of blood AMM-ULN and MELD score alone, the AUC of the combined model of AMM-ULN, MELD score and education exhibited better predictive performance in determining the presence of MHE was 0.755, the specificity and sensitivity was 85.2% and 55.7%, respectively. Hosmer-Lemeshow test and calibration curve showed that the model had good calibration ( P=0.733). The AUC for internal validation of the combined model for diagnosing MHE was 0.752. In the validation set, the AUC of the combined model for diagnosing MHE was 0.794, and Hosmer-Lemeshow test showed good calibration ( P=0.841). Conclusion:Use of the combined model including AMM-ULN, MELD score and education could improve the predictive efficiency of MHE among patients with compensated cirrhosis.

Objective:To analyze the influential factors of hypoalbuminemia in patients with preeclampsia and observe the pregnancy outcomes.Methods:The clinical data of 237 pregnant women with preeclampsia who received treatment in The Sixth Affiliated Hospital of Guangzhou Medical University (Qingyuan People's Hospital) from July 2018 to December 2020 were retrospectively collected and analyzed. These patients were divided into hypoproteinemia (observation group) and no hypoproteinemia (control group) groups according to whether they had hypoproteinemia. The general situation, clinical data, and adverse maternal and infant outcomes were statistically analyzed. Risk factors of hypoalbuminemia were analyzed using a logistic regression model. The predictive efficacy was evaluated using the receiver operating characteristic curve.Results:There were no significant differences in general data between the two groups (all P > 0.05). Multivariate analysis showed that D-dimer ( OR = 1.25, P = 0.004), 24-hour urinary protein ( OR = 1.29, P < 0.001), and total bile acid ( OR = 1.08, P = 0.010) were the independent risk factors for hypoproteinemia in preeclampsia. The predictive efficacy of these three indicators (area under the receiver operating characteristic curve = 0.855, P < 0.001) was greater than that of a single indicator. The incidences of adverse maternal and infant outcomes including placental abruption (9.4%, P = 0.019), liver and kidney dysfunction (34.4%, P < 0.001), pleural and ascitic fluid (28.1%, P = 0.001), fetal intrauterine growth restriction (50.0%, P = 0.001), fundus lesions (6.2%, P = 0.018), HELLP syndrome (9.4%, P = 0.019), mild neonatal asphyxia (15.6%, P = 0.022), severe asphyxia (6.2%, P = 0.049), metabolic acidosis (12.5%, P = 0.001), intrauterine infection (12.5%, P = 0.004), and neonatal hospitalization for more than 20 days (37.5%, P < 0.001) were greater in the observation group compared with the control group. There were no significant differences in postpartum hemorrhage, eclampsia, respiratory distress syndrome, fetal loss, and neonatal death between the two groups (all P > 0.05). Conclusion:D-dimer, 24-hour urinary protein, and total bile acid are independent risk factors for hypoproteinemia in preeclampsia. Patients with preeclampsia complicated by hypoproteinemia have a high risk of adverse maternal and infant outcomes.

Objective:To investigate the current sedation level of patients with mechanical ventilation in ICU, and to explore the influence of early different sedation levels on clinical outcomes, so as to provide theoretical basis for better guidance of clinical sedation evaluation and implementation of sedation strategy management.Methods:This study was a retrospective longitudinal study. The 201 patients with invasive mechanical ventilation who underwent sedation in the Department of Intensive Care Medicine of the First Affiliated Hospital of Guangxi Medical University from January to December 2021 were selected by convenience sampling method. According to the results of Richmond Agitation-Sedation Scale(RASS), the patients were divided into deep sedation group (98 cases) and shallow sedation group (103 cases). The influencing factors of endotracheal intubation retention time and outcome were investigated by Cox multifactor analysis.Results:In the early sedation ≤48 h after the start of mechanical ventilation, 63.2%(2 143/3 389) of patients with invasive mechanical ventilation had a RASS score of shallow sedation, 35.2%(1 194/3 389) of patients with deep sedation, and 1.5%(52/3 389) of patients with insufficient sedation. Cox multivariate regression analysis showed that age, sedation level, duration of invasive mechanical ventilation and continuous renal replacement therapy were the factors influencing the indentation time of tracheal insertion ( χ2 values were 4.73 to 74.31, all P<0.05); early deep sedation was a risk factor for delayed extubation ( HR=0.499, 95% CI 0.276-0.903, P<0.05); gender, sedation level, invasive mechanical ventilation duration, acute physiology and chronic health evaluation Ⅱ scores, admission mode, continuous renal replacement therapywere the influencing factors of patient outcomes ( χ2 values were 4.41 to 26.20, all P<0.05). The deeper the sedation, the worse the patient outcomes ( HR=0.568, 95% CI 0.335-0.963 all P<0.05) . Conclusions:The early sedation level is related to the retention time and outcome of tracheal intubation in ICU patients with mechanical ventilation, and different sedation levels affect the clinical outcome of patients. The retention time of tracheal intubation in patients with shallow sedation was shortened, which was beneficial to the outcome of patients.Therefore, sedation evaluation should be strengthened in clinical work, and sedation methods should be selected according to the needs of patients. In the absence of contraindications, the shallow sedation strategy should be implemented as soon as possible. This study provides some reference and theoretical basis for the formulation and management of clinical sedation strategies.

Objective:To explore if protective effects of dapagliflozin (Dapa) administration on attenuating DOX-induced myocardial injury in rats.Methods:A total of 30 specific pathogens free grade 8 week old male Sprague Dawley rats. Rats were randomly divided into three groups. Control group (Con group, n = 5), rats received intraperitoneal saline (1.25 ml/kg) injection once per week plus saline (8 mg/kg) daily via gavage for 6 weeks. Dox group ( n = 15) rats received intraperitoneal Dox (2.5 mg/kg) injection once per week plus saline (8 mg/kg) daily via gavage for 6 weeks. Dox + Dapa group ( n = 10), rats received intraperitoneal Dox (2.5 mg/kg) injection once per week plus Dapagliflozin (4 mg/kg) daily via gavage for 6 weeks, observed to week 10. Survival status, echocardiography, pathology, and expression of Bcl-2, Bax gene and protein were observed. Results:The survival rate of ats in Con, Dox, and Dapa+Dox groups was 100.0%, 66.7% and 90.0% respectively. The echocardiography were performed in Con, Dox, and Dapa+Dox groups left ventricular ejection fraction was (95.40 ± 2.51)%, (83.09 ± 4.92)% and (91.71 ± 3.45)%, respectively; left ventricular fraction shortening was (66.80 ± 7.43)%, (47.27 ± 5.10)% and (59.43 ± 6.92)%, respectively; Both indexes in Dapa+Dox group was higher than that in Dox group, but lower than that in Con group, all P<0.05; Left ventricular end-diastolic diameter was (4.80 ± 0.83) mm, (5.90 ± 0.83) mm and (4.85 ± 0.69) mm respectively; left ventricular end-systolic diameterwas (1.80 ± 0.44) mm, (2.90 ± 0.53) mm and (2.00 ± 0.57) mm in Con, Dox, and Dapa + Dox groups, respectively; Both indexes in Dapa + Dox group was decreased than that in Dox group, but Dapa + Dox group was increased than that in Con group, all P<0.05. Pathologic changes have been shown that myocardial fibers arranged neatly in the Con group under HE staining, while those broken myocardial fibers disordered arranged in the Dox group, and those changes in the Dapa + Dox group were slightly relieved than that in Dox group. The collagen volume fraction of rats in Con, Dox and Dapa+Dox groups were (2.64 ± 1.04)%, (16.85 ± 1.70)% and (6.75 ± 1.89)% under sirius red staining, Dapa+Dox group was lower than that in Dox group but higher than that in Con group, all P<0.05. Pathologic changes under transmission electron microscope have been shown that a few of normal structure mitochondria in the Con group. A large number of swollen mitochondria with disappeared mitochondrial crest in the Dox group; but neatly arranged with mitochondrial crest blurred in the Dapa+Dox group. The quantitative real-time PCR was used to detected Bcl-2 and Bax, there were 0.93 ± 0.09, 0.35 ± 0.30 and 0.89 ± 0.25 in Bcl-2, 0.99 ± 0.10, 3.10 ± 0.10 and 0.86 ± 0.04) in Bax, while Bcl-2/Bax 0.94 ± 0.17, 0.11 ± 0.06 and 1.03 ± 0.27, respectively. The westernblot was used to detected Bcl-2 and Bax, there were 1.00 ± 0.18, 0.32 ± 0.20 and 1.30 ± 0.41 in Bcl-2, 0.66 ± 0.11, 2.44 ± 0.66 and 0.90 ± 0.61 in Bax, while Bcl-2/Bax: 1.50 ± 0.18, 0.12 ± 0.05 and 1.80 ± 0.82, respectively; the above results shown that both myocardial Bax mRNA and protein expression in Dox group were higher than that in Dapa + Dox group and Con group, both P<0.05, and there was no difference in the two later groups, P>0.05; both the myocardial Bcl-2 mRNA and protein expression in Dox group were lower than that in Dapa+Dox group and Con group, both P<0.05, and there was no difference between two later groups, P>0.05; Bcl-2/Bax in Dox group was significantly lower thanthat in Dapa+Dox groupand Con group, both P<0.05, and there was no difference between Dapa+Dox group and Con group, P>0.05. Conclusions:Simultaneous dapagliflozin treatment significantly attenuated DOX-induced cardiotoxicity, which might be related to prevent myocardial apoptosis.

The emergence of SARS-CoV-2 variants of concern and repeated outbreaks of coronavirus epidemics in the past two decades emphasize the need for next-generation pan-coronaviral therapeutics. Drugging the multi-functional papain-like protease (PLpro) domain of the viral nsp3 holds promise. However, none of the known coronavirus PLpro inhibitors has been shown to be in vivo active. Herein, we screened a structurally diverse library of 50,080 compounds for potential coronavirus PLpro inhibitors and identified a noncovalent lead inhibitor F0213 that has broad-spectrum anti-coronaviral activity, including against the Sarbecoviruses (SARS-CoV-1 and SARS-CoV-2), Merbecovirus (MERS-CoV), as well as the Alphacoronavirus (hCoV-229E and hCoV-OC43). Importantly, F0213 confers protection in both SARS-CoV-2-infected hamsters and MERS-CoV-infected human DPP4-knockin mice. F0213 possesses a dual therapeutic functionality that suppresses coronavirus replication via blocking viral polyprotein cleavage, as well as promoting antiviral immunity by antagonizing the PLpro deubiquitinase activity. Despite the significant difference of substrate recognition, mode of inhibition studies suggest that F0213 is a competitive inhibitor against SARS2-PLpro via binding with the 157K amino acid residue, whereas an allosteric inhibitor of MERS-PLpro interacting with its 271E position. Our proof-of-concept findings demonstrated that PLpro is a valid target for the development of broad-spectrum anti-coronavirus agents. The orally administered F0213 may serve as a promising lead compound for combating the ongoing COVID-19 pandemic and future coronavirus outbreaks.
Animals ; Coronavirus Papain-Like Proteases/antagonists & inhibitors* ; Cricetinae ; Humans ; Mice ; Pandemics ; SARS-CoV-2/enzymology* ; COVID-19 Drug Treatment

Objective: To analyze the clinical characteristics of children with Burkitt lymphoma (BL) and to summarize the mid-term efficacy of China Net Childhood Lymphoma-mature B-cell lymphoma 2017 (CNCL-B-NHL-2017) regimen. Methods: Clinical features of 436 BL patients who were ≤18 years old and treated with the CNCL-B-NHL-2017 regimen from May 2017 to April 2021 were analyzed retrospectively. Clinical characteristics of patients at disease onset were analyzed and the therapeutic effects of patients with different clinical stages and risk groups were compared. Survival analysis was performed by Kaplan-Meier method, and Cox regression was used to identify the prognostic factors. Results: Among 436 patients, there were 368 (84.4%) males and 68 (15.6%) females, the age of disease onset was 6.0 (4.0, 9.0) years old. According to the St. Jude staging system, there were 4 patients (0.9%) with stage Ⅰ, 30 patients (6.9%) with stage Ⅱ, 217 patients (49.8%) with stage Ⅲ, and 185 patients (42.4%) with stage Ⅳ. All patients were stratified into following risk groups: group A (n=1, 0.2%), group B1 (n=46, 10.6%), group B2 (n=19, 4.4%), group C1 (n=285, 65.4%), group C2 (n=85, 19.5%). Sixty-three patients (14.4%) were treated with chemotherapy only and 373 patients (85.6%) were treated with chemotherapy combined with rituximab. Twenty-one patients (4.8%) suffered from progressive disease, 3 patients (0.7%) relapsed, and 13 patients (3.0%) died of treatment-related complications. The follow-up time of all patients was 24.0 (13.0, 35.0) months, the 2-year event free survival (EFS) rate of all patients was (90.9±1.4) %. The 2-year EFS rates of group A, B1, B2, C1 and C2 were 100.0%, 100.0%, (94.7±5.1) %, (90.7±1.7) % and (85.9±4.0) %, respectively. The 2-year EFS rates was higher in group A, B1, and B2 than those in group C1 (χ²=4.16, P=0.041) and group C2 (χ²=7.21, P=0.007). The 2-year EFS rates of the patients treated with chemotherapy alone and those treated with chemotherapy combined with rituximab were (79.3±5.1)% and (92.9±1.4)% (χ²=14.23, P<0.001) respectively. Multivariate analysis showed that stage Ⅳ (including leukemia stage), serum lactate dehydrogenase (LDH)>4-fold normal value, and with residual tumor in the mid-term evaluation were risk factors for poor prognosis (HR=1.38,1.23,8.52,95%CI 1.05-1.82,1.05-1.43,3.96-18.30). Conclusions: The CNCL-B-NHL-2017 regimen show significant effect in the treatment of pediatric BL. The combination of rituximab improve the efficacy further.
Adolescent ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Burkitt Lymphoma/drug therapy* ; Child ; Disease-Free Survival ; Female ; Humans ; Lactate Dehydrogenases ; Lymphoma, B-Cell/drug therapy* ; Male ; Prognosis ; Retrospective Studies ; Rituximab/therapeutic use* ; Treatment Outcome