Objective To investigate the effect of fibroblast growth factor receptor 3(FGFR3)on articular cartilage superficial zone cells(SPZCs).Methods C57 mice were randomly divided into two groups:a sham operated group(sham group)and a group of surgically induced unstable medial meniscus model group(DMM group).The histological morphology of articular cartilage was microscopied by Safranin O/Fast Green-stained in 4 weeks and 8 weeks after surgery.Apoptosis and FGFR3 protein expression were detected by immunohistochemical staining mi-croscopy.Primary SPZCs were separated and randomly divided into control group and Fgfr3 knockdown treatment group.The genes and protein expression related to chondrocyte extra cellular matrix synthesis,degradation and chondrocytehypertrophy were detected by RT-qPCR and Western blot.Results Compared with the sham group,the keen cartilage of mice in DMM group showed a pioneer damage of SPZCs after surgery;Immunohistochemistry results showed an increase in chondrocyte apoptosis and a decrease in expression of MMP-13 and FGFR3(P＜0.05).Primary SPZCs were transfected with small interfering RNA(siRNA)to knockdown Fgfr3;RT-qPCR results showed that the mRNA expression of genes related to the synthesis of cartilage extracellular matrix aggrecan and Col2 was reduced;And the mRNA expression of extracellular matrix degradation-related genes Mmp13 and Adamts5 was increased.The mRNA expression of chondrocyte hypertrophy-related genes Col10 and Mmp13 was increased.Western blot and RT-qPCR results were consistent and the expression l of MMP13 protein was significantly increased,while the expression of collagenⅡand aggrecan protein was significantly decreased(P＜0.05).Conclusions Knockdown of Fgfr3 induces damage to primary SPZCs in mice resulting in early osteoarthritis(OA)development.

Objective:To study the short-term clinical outcomes of different courses of antenatal corticosteroids (ACS) for preterm twins.Methods:From January 2017 to December 2021, preterm twins with gestational age (GA) 24-34 weeks admitted to the neonatal ward of our hospital and received ACS were retrospectively studied. The infants were assigned into single-course group, partial-course group and multiple-course group according to ACS courses. The short-term clinical outcomes were compared among the groups. SPSS software version 25.0 was used for statistical analysis.Results:A total of 286 infants were enrolled in this study, including 128 in single-course group, 89 in partial-course group and 69 in multiple-course group. Compared with single-course group, the risks of neonatal respiratory distress syndrome (RDS) in both partial-course group ( OR=2.332, 95% CI 1.028-5.293, P=0.043) and multiple-course group ( OR=3.872, 95% CI 1.104-13.584, P=0.034) were higher. The birth length in multiple-course group ( β=-0.016, 95% CI -0.029 - -0.002, P=0.024) was lower than single-course group. Conclusions:The risks of neonatal RDS in preterm twins are higher in partial-course and multiple-course of ACS. A full course of ACS should be used to prevent neonatal RDS until further evidence of effectiveness is available.

Objective:To construct a classification and regression tree which can be used to guide the tracheostomy for traumatic cervical spinal cord injury (TCSCI) based on the identification of the risk factors for TCSCI.Methods:The 498 patients with TCSCI were retrospectively analyzed who had been treated at Department of Orthopedics, The Second Hospital Affiliated to Army Medical University from January 2009 to December 2018. There were 403 males and 86 females, with an age of (50.2±13.6) years. Of the patients, 69 received tracheostomy and 420 did not. The gender, age, smoking history, injury cause, neurological level of injury (NLI), American Spinal Cord Injury Association (ASIA) grade, injury severity score (ISS), thoracic injuries, prior pulmonary diseases, prior basic diseases, and operative approaches of the patients were statistically analyzed by single factor analysis. After the independent risk factors for tracheostomy were analyzed by binary logistic regression, the classification and regression tree was developed which could be used to guide the tracheostomy.Results:The logistic regression analysis showed age>50 years ( OR=4.744, 95% CI: 1.802 to 12.493, P=0.002), NLI at C 4 and above ( OR=23.662, 95% CI: 8.449 to 66.268, P<0.001), ASIA grade A ( OR=40.007, 95% CI: 12.992 to 123.193, P<0.001), and ISS score>16 ( OR=10.502, 95% CI: 3.909 to 28.211, P<0.001) were the independent risk factors for the tracheotomy. The classification and regression tree revealed that ASIA grade A and NLI at C 4 and above were the first and second decision nodes, which had a strong predictive effect on tracheostomy. 86.84% of the patients with ASIA grade A and NLI at C 4 and above underwent tracheostomy. Conclusion:Our classification and regression tree shows that NLI at C 4 and above and ASIA grade A have a strong guiding effect on tracheotomy for TCSCI.

Objective:To investigate the distribution and antimicrobial resistance profile of clinical bacteria isolated from blood culture in China.Methods:The clinical bacterial strains isolated from blood culture from member hospitals of Blood Bacterial Resistant Investigation Collaborative System (BRICS) were collected during January 2018 to December 2019. Antibiotic susceptibility tests were conducted with agar dilution or broth dilution methods recommended by US Clinical and Laboratory Standards Institute (CLSI). WHONET 5.6 was used to analyze data.Results:During the study period, 14 778 bacterial strains were collected from 50 hospitals, of which 4 117 (27.9%) were Gram-positive bacteria and 10 661(72.1%) were Gram-negative bacteria. The top 10 bacterial species were Escherichia coli (37.2%), Klebsiella pneumoniae (17.0%), Staphylococcus aureus (9.7%), coagulase-negative Staphylococci (8.7%), Pseudomonas aeruginosa (3.7%), Enterococcus faecium (3.4%), Acinetobacter baumannii(3.4%), Enterobacter cloacae (2.9%), Streptococci(2.8%) and Enterococcus faecalis (2.3%). The the prevalence of methicillin-resistant S. aureus (MRSA) and methicillin-resistant coagulase-negative Staphylococcus were 27.4% (394/1 438) and 70.4% (905/1 285), respectively. No glycopeptide-resistant Staphylococcus was detected. More than 95% of S. aureus were sensitive to amikacin, rifampicin and SMZco. The resistance rate of E. faecium to vancomycin was 0.4% (2/504), and no vancomycin-resistant E. faecalis was detected. The ESBLs-producing rates in no carbapenem-resistance E. coli, carbapenem sensitive K. pneumoniae and Proteus were 50.4% (2 731/5 415), 24.6% (493/2001) and 35.2% (31/88), respectively. The prevalence of carbapenem-resistance in E. coli and K. pneumoniae were 1.5% (85/5 500), 20.6% (518/2 519), respectively. 8.3% (27/325) of carbapenem-resistance K. pneumoniae was resistant to ceftazidime/avibactam combination. The resistance rates of A. baumannii to polymyxin and tigecycline were 2.8% (14/501) and 3.4% (17/501) respectively, and that of P. aeruginosa to carbapenem were 18.9% (103/546). Conclusions:The surveillance results from 2018 to 2019 showed that the main pathogens of bloodstream infection in China were gram-negative bacteria, while E. coli was the most common pathogen, and ESBLs-producing strains were in majority; the MRSA incidence is getting lower in China; carbapenem-resistant E. coli keeps at a low level, while carbapenem-resistant K. pneumoniae is on the rise obviously.

The blood-brain barrier (BBB) constitutes a major obstacle to effective delivery of drugs to the brain. Recent technological advances have led to improvements in brain-targeted drug delivery. In this review, we summarize existing technologies for efficient drug delivery across the BBB. We discuss the mecha-nisms of current BBB-based drug delivery strategies and introduce prospects for application in brain-targeted delivery of traditional Chinese medicine. We highlight the use of physical techniques for brain-targeted drug delivery, including electroporation, ultrasound, magnetophoresis, microneedles, microwaves, and laser. The characteristics of these techniques and relevant studies employing these approaches are discussed. In general, microneedles, lasers, ultrasound, electroporation, magnetophoresis, and microwaves are effective for drug delivery across the BBB. Notably, the synergistic effects of multiple approaches are superior to the additive effects of each technique in isolation. Our review provides guidance for the practical application of brain-targeted drug delivery techniques in an efficient and safe manner.

Objective:To investigate the distribution and antimicrobial resistance profile of clinical bacteria isolated from blood culture in China.Methods:The clinical bacterial strains isolated from blood culture from member hospitals of Blood Bacterial Resistant Investigation Collaborative System (BRICS) were collected during January 2016 to December 2017. Antibiotic susceptibility tests were conducted by agar dilution or broth dilution methods recommended by US Clinical and Laboratory Standards Institute (CLSI) 2019. WHONET 5.6 was used to analyze data.Results:During the study period, 8 154 bacterial strains were collected from 33 hospitals, of which 2 325 (28.5%) were Gram-positive bacteria and 5 829 (71.5%) were Gram-negative bacteria. The top 10 bacterial species were Escherichia coli (34.7%), Klebsiella pneumoniae (15.8%), Staphylococcus aureus (11.3%), coagulase-negative Staphylococci (7.4%), Acinetobacter baumannii (4.6%), Pseudomonas aeruginosa (3.9%), Enterococcus faecium (3.8%), Streptococci (2.9%), Enterobacter cloacae (2.7%) and Enterococcus faecalis (2.5%). Methicillin-resistant Staphylococcus aureus (MRSA) and methicillin-resistant coagulase-negative Staphylococcus (MRCNS) accounted for 34.2%(315/922) and 77.7%(470/605), respectively. No vancomycin-resistant Staphylococcus was detected. The resistance rate of Enterococcus faecium to vancomycin was 0.6%(2/312), and no vancomycin-resistant Enterococcus faecium was detected. The ESBLs-producing rates in Escherichia coli, Klebsiella pneumoniae and Proteus were 55.7%(1 576/2 831), 29.9%(386/1 289) and 38.5%(15/39), respectively. The incidences of carbapenem-resistance in Escherichia coli, Klebsiella pneumoniae were 1.2%(33/2 831), 17.5%(226/1 289), respectively. The resistance rates of Acinetobacter baumannii to polymyxin and tigecycline were 14.8%(55/372) and 5.9%(22/372) respectively, and those of Pseudomonas aeruginosa to polymyxin and carbapenem were 1.3%(4/315) and 18.7%(59/315), respectively. Conclusion:The surveillance results from 2016 to 2017 showed that the main pathogens of blood stream infection in China were gram-negative bacteria, while Escherichia coli was the most common pathogen; the MRSA incidence was lower than other surveillance data in the same period in China; carbapenem-resistant Escherichia coli was at a low level during this surveillance, while carbapenem-resistant Klebsiella pneumoniae is on the rise.

OBJECTIVE: To find the pathogenies and risk factors related to surgical intensive care unit (SICU) readmission for patients who underwent hepatobiliary-pancreatic surgery, and to develop a predictive model for determining patients who are likely to be readmitted to SICU. METHODS: The patients who admitted to SICU of the Affiliated Hospital of Qingdao University from January 2013 to August 2018; who first stayed in SICU after hepatobiliary-pancreatic surgery; who were assessed and discharged from SICU by surgeons and SICU physicians after treatment, and then transferred to SICU again because of the change of their condition were enrolled. The unintended return to SICU within 3 days and 7 days were recorded. Patients who returned to SICU within 7 days were studied for the pathogenies, risk factors and predictive model of returning to SICU, and non-returning patients were enrolled according to 1:1 as the controls. A total of 43 indicators were divided into five categories, including general clinical data, medical history, surgical indicators before first admission of SICU, length of first SICU stay, and other indicators on the day of first discharge from the SICU. Logistic regression was used to screen the risk factors associated with SICU readmission, then the Nomogram diagram was drawn by using the R 3.4.1 software for predicting SICU readmission, and the classification performance of Nomogram was evaluated by self-help sampling test. RESULTS: Of the 763 patients discharged from the SICU, 2.10% (16/763) of them were readmitted within 3 days and 3.28% (25/763) were readmitted within 7 days to the SICU unexpectedly. The pathogenies of SICU readmission within 7 days included infection [56.00% (14/25)], heart failure [16.00% (4/25)], infarction [12.00% (3/25)], bleeding [12.00% (3/25)], and sutures splitting [4.00% (1/25)]. The pathogenies of SICU readmission within 3 days included infection [56.25% (9/16)], heart failure [18.75% (3/16)], infarction [12.50% (2/16)], and bleeding [12.50% (2/16)]. Nomogram analysis showed that the risk factors associated with unplanned SICU readmission were length of first SICU stay, history of hypertension, and activity of daily living (ADL) score, white blood cell count (WBC), arterial partial pressure of oxygen (PaO₂), prothrombin time (PT), fibrinogen (FIB) on the day of first SICU discharge. Self-help sampling test was carried out on the Nomogram map, and the results showed that the coherence index (C-index) was 0.962 [95% confidence interval (95%CI) = 0.869-1.057]. The classification performance of the model was good. CONCLUSIONS The common pathogenies of SICU readmission for patients who underwent hepatobiliary-pancreatic surgery were infection, heart failure, infarction and bleeding. Risk factors of readmission after SICU discharge included the length of first SICU stay, history of hypertension, and ADL score, WBC, PaO₂, PT, FIB on the day of first SICU discharge. The model consisted of above risk factors showed a good performance in predicting the probability of readmission after SICU discharge for patients who underwent hepatobiliary-pancreatic surgery.
Biliary Tract Diseases/surgery* ; Digestive System Surgical Procedures/adverse effects* ; Humans ; Intensive Care Units ; Liver Diseases/surgery* ; Models, Statistical ; Pancreatic Diseases/surgery* ; Patient Readmission/statistics & numerical data* ; Postoperative Complications/therapy* ; Risk Factors

Objective To analyze the distribution and antimicrobial resistance profile of clinical bacterial strains isolated from blood culture in China.Methods Clinical bacterial strains isolated from blood culture from participating hospitals of Blood Bacterial Resistance Investigation Collaborative System (BRICS) during January 2014 to December 2015 were collected.Antibiotic susceptibility tests were conducted with agar dilution or broth dilution methods as recommended by US Clinical and Laboratory Standards Institute(CLSI)2018.The data were analyzed with Whonet 5.6 software.Results During the study period,4 801 clinical bacterial isolates were collected from 26 hospitals,of which 1 798 (37.5％) were Gram-positive bacteria and 3 003 (62.5％) were gram-negative bacteria.The top 10 isolates were Escherichia coli (33.8％),coagulase-negative Staphylococcus (19.0％),Klebsiella pneumoniae (11.9％),Staphylococcus aureus (10.1％),Acinetobacter baumannii (4.0％),Pseudomonas aeruginosa (3.8％),Streptococcus (3.0％),Enterobacter sulcus (2.9％),Enterococcus faecium (2.8％) and Enterococcus faecalis (1.8％).Methicillin-resistant Staphylococcus aureus (MRSA) and methicillinresistant coagulase-negative Staphylococcus (MRCNS) accounted for 33.9％ (165/487) and 56.9％ (520/913) of Staphylococcus aureus and coagulase-negative Staphylococcus respectively.No vancomycinresistant Staphylococcus was detected.The resistance rate of Enterococcus faecium to vancomycin was 0.7％ (1/135),and no vancomycin-resistant Enterococcus faecaliss was detected.The positive rates of extendedspectrum β-1actamases(ESBLs)-producing Escherichia coli,Klebsiella pneumoniae and Proteus were 56.9％ (923/1 621),30.1％ (172/572) and 29.2％ (7/24),respectively.The positive rates of carbapenemresistant Escherichia coli,Klebsiella pneumoniae,Enterobacter,Salmonella and Citrobacter were 1.2％ (20/1 621),7.2％ (41/572),4.3％ (6/141),1.5％ (1/67) and 2.9％ (1/34),respectively.The resistance rates of Acinetobacter baumannii to polymyxin and tegacycline were 2.6％ (5/190) and 8.9％ (17/190)respectively,and that of Pseudomonas aeruginosa to polymyxin and fosfomycin were 1.1％ (2/183)and 0.6％ (1/183),respectively.Conclusions The surveillance results from 2014 to 2015 show that the main pathogens of blood stream infection in China are Gram-negative bacteria,while Escherichia coli is the most common pathogen,the detection rate of MRSA is lower than other surveillance data in the same period in China;carbapenem-resistant Klebsiella pneumoniae and Escherichia coli are at a low level as shown in this surveillance.

Objective To confirm the predictive value of diaphragm thickening fraction (DTF) on successful weaning by bedside ultrasound in patients with myasthenia gravis crisis. Methods A prospective study was conducted. The patients with myasthenia gravis crisis undergoing mechanical ventilation admitted to Department of Critical Care Medicine of the Affiliated Hospital of Qingdao University from March 2015 to February 2017 were enrolled. All patients underwent a low level pressure support mode of spontaneous breathing test (SBT), and rapid shallow breathing index (RSBI) was recorded. The indicators of right diaphragm thickness at the end of inspiration (DTei) and expiration (DTee) were determined by bedside ultrasound at 5 minutes and 60 minutes of SBT, and DTF was calculated, the changes in above parameters were observed during SBT. The patients were divided into successful weaning group and failure weaning group, and the differences in above indexes were compared between the two groups. Receiver operating characteristic curve (ROC) was used to evaluate the predictive value of DTF and RSBI at 60 minutes of SBT on successful weaning. Results A total of 37 patients were enrolled in the study. Ultrasonic measurement data of 63 person-times at 5 minutes of SBT and 50 at 60 minutes of SBT were obtained. There were no statistical differences in RSBI, DTei, DTee, and DTF at 5 minutes of SBT between successful weaning group (n = 33) and failure weaning group (n = 30). At 60 minutes of SBT, compared with successful weaning group (n = 33), the patients in failure weaning group (n = 17) had a higher RSBI (times·min-1·L-1: 80.41±29.08 vs. 63.94±23.84, t = 2.146, P = 0.037), and lower DTee, DTei and DTF [DTee (mm): 22.00±6.25 vs. 25.45±4.99, t = 2.127, P = 0.039; DTei (mm): 27.94±6.19 vs. 38.48±6.15,t = 5.731, P = 0.000; DTF: (24.46±14.11)% vs. (62.04±30.21)%, t = 4.845, P = 0.000]. There were no statistical differences in RSBI, DTei, DTee, and DTF between 5 minutes and 60 minutes of SBT in 33 person-time successful weaning (all P > 0.05). In 17 person who had 60 minutes of SBT but failed weaning, the RSBI at 60 minutes of SBT was significantly higher than that at 5 minutes (times·min-1·L-1: 80.41±29.08 vs. 57.29±22.46, t = 2.400, P = 0.029), and DTei and DTF were significantly decreased [DTei (mm): 27.94±6.19 vs. 35.35±6.84, t = 3.024, P = 0.000; DTF:(24.46±14.11)% vs. (61.89±23.97)%, t = 5.810, P = 0.000], but the change of DTee during SBT showed no statistical significance. ROC curve analysis showed that the area under ROC curve (AUC) of DTF at 60 minutes of SBT for predicting successful weaning was 0.898; when DTF ≥ 27.9% as the cut-off point, the sensitivity was 93.9%, specificity was 70.6%. The AUC of RSBI for predicting successful weaning was 0.669; when RSBI ≥ 86.50 times·min-1·L-1 as the cut-off point, the sensitivity was 81.8%, specificity was 52.9%. Conclusion DTF at 60 minutes of SBT is the effective index of successful weaning prediction in mechanical ventilation patients with myasthenia gravis crisis.

Objective To evaluate the application of clinical cases related problem-based-learning (PBL) method in critical care medical standardized resident training program. Methods 84 residents were randomly divided into experimental group (n=42) and control group (n=42) by lottery way. The experimental group received PBL process during clinical case analysis while the control group learned completely through traditional teaching method . The residents' clinical competence were assessed by multiple scale mixed method including question bank examination (QBE), case-based discussion (CBD), direct observation of procedural skills (DOPS), simulation etc, and Likert-type scale questionnaire was used to evaluate the feedback of training residents. SPSS 17.0 was used to do line t test to the data of both groups. Results Finally 84 residents finished the study. There were no difference in the general conditions in two groups. The PBL group achieved higher examination score during QBE [(80.26 ±8.89) vs. (86.10 ±9.32)], CBD [(84.83±5.43) vs. (75.36±6.06)], DOPS [(88.81±6.68) vs. (82.70±6.98)], simulation [(79.86±10.09) vs.(72.71±9.30)]. Except two groups residents all gave high scores in enhancing cross connection in clinical knowledge [(4.786±0.470) vs. (4.571±0.859), P=0.16], and the questionnaire results showed that the resi-dents of PBL group gave higher points in exciting autonomous learning, improving clin-ical analysis ability, accelerating clinical thinking establish, developing independent thinking habits, improving the clinical communication skills and teamwork ability (P<0.05). Conclusion The clinical cases related PBL method can improve the training effects during critical care medical standardized resident training program. It can be used broadly after adapting modification in critical care medical education.