Objective:To analyze and summarize the operational mechanisms of the " National Facility for Translational Medicine (Shanghai)" (referred to as the Shanghai Facility), providing reference for the high-quality construction, management, and utilization of such facilities.Methods:Using the construction and operation of the Shanghai facility as a case study, this paper analyzed and discussed the facility's construction content, functional positioning, operational management systems, operational outcomes, in the meanwhile summarizing experience in construction and running of the facility.Results:Since the Shanghai facility was completed and officially put into operation in December 2020, significant achievements had been made in platform construction and operation.Conclusions:The successful operation of the Shanghai facility provides valuable experience for the construction of national major scientific and technological infrastructure in the field of translational medicine. In the future, its construction and management can be further improved through measures such as multi-channel fundraising, building-up of a multidisciplinary translational medicine talent team, and establishment of reasonable facility assessment criteria and talent evaluation standards.

Objective To investigate the effect of tritiated water on the immune system of zebrafish and its potential molecular mechanism. Methods Zebrafish embryos (2.5 to 3 hours post-fertilization [hpf]) were exposed to 3.7 × 10⁴ Bq/mL tritiated water (tritiated water group), and those exposed to E3 culture medium were used as the control group. The mortality rate, hatching rate, deformity rate, heart rate, body length, yolk sac area, neutrophil count in the tail, immune-related gene expression, and immune-related protein expression of zebrafish in the two groups were determined. Then transcriptome technology was used to further analyze the possible mechanism of tritiated water affecting the immune system of zebrafish. Results Compared with the control group, zebrafish at 72 hpf in the tritiated water group had no significant changes in the mortality rate, hatching rate, deformity rate, body length, and yolk sac area((t = 0.9045, 0.5000, 1.0000, 0.7238, 0.0337, P = 0.4169, 0.6433, 0.3739, 0.4785, 0.9735), but had significantly increased heart rate(t = 4.575，P = 0.002). At 4 days post-fertilization (dpf), the neutrophil count in the tail of zebrafish in the tritiated water group was significantly increased(t = 2.563，P = 0.0196), the mRNA expression of TNF-α was significantly decreased(t = 2.891, P = 0.045), the protein expression of nuclear factor-kappa B (NF-κB) was significantly increased(t = 3.848, P = 0.018), and the protein expression of NLRP3 was significantly decreased(t = 14.98, P = 0.001). At 7 dpf, the neutrophil count in the tail and the protein expression levels of NF-κB, NLRP3, and interleukin-1β were significantly decreased(t = 3.772, 7.048, 15.620, 4.423, P = 0.014, 0.002, 0.0001, 0.012). Transcriptome sequencing revealed that differentially expressed genes were mainly enriched in the “neutrophil activation” and “platelet activation pathways” at 4 dpf and in the “neutrophil apoptosis”, “ferroptosis”, and “necroptosis” pathways at 7 dpf. Conclusion Tritiated water exposure induces a temporally dynamic immune response in zebrafish, potentially affecting immune homeostasis by regulating neutrophil activation and apoptosis, as well as the expression of NF-κB and NLRP3.

Objective To develop a gas chromatography-tandem mass spectrometry(GC-MS/MS)method for the simultaneous determination of ephedrine and pseudoephedrine in urine.Methods Urine samples containing ephedrine and pseudoephedrine components were extracted with ethyl acetate,centrifuged to collect the supernatant and evaporated to dryness under a nitrogen stream and then derivatized with heptafluorobutyric anhydride 60 μL at 70 ℃ for 30 min,and re-evaporated under nitrogen,and then solubilized with 50 μL of methanol,and then analyzed by GC-MS/MS.Results The method demonstraed excellent linearity for ephedrine(0.05～10 μg/mL,r=0.999 8)and pseudoephedrine(0.02～5 μg/mL,r=0.999 5).Extraction recoveries ranged from 89.4％～95.8％(ephedrine)and 90.3％～93.8％(pseudoephedrine).Limits of detection and quantification of ephedrine and pseudoephedrine were 0.005 μg/mL and 0.01 μg/mL,the intra-day precision and accuracy were less than 5.87％and 9.56％,respectively,and the inter-day precision and accuracy were less than 7.54％and 9.27％,respectively.The stability of ephedrine and pseudoephedrine in urine in 15 d was good under the conditions of room temperature and-20 ℃.Conclusion The GC-MS/MS analytical method for the analysis of ephedrine and pseudoephedrine components in urine established in this study is accurate,stable and sensitive,which can provide data technical support for the forensic toxicological analysis of amphetamine-type drugs or new psychoactive substances in the cathinone group.

Objective To develop a gas chromatography-tandem mass spectrometry(GC-MS/MS)method for the simultaneous determination of ephedrine and pseudoephedrine in urine.Methods Urine samples containing ephedrine and pseudoephedrine components were extracted with ethyl acetate,centrifuged to collect the supernatant and evaporated to dryness under a nitrogen stream and then derivatized with heptafluorobutyric anhydride 60 μL at 70 ℃ for 30 min,and re-evaporated under nitrogen,and then solubilized with 50 μL of methanol,and then analyzed by GC-MS/MS.Results The method demonstraed excellent linearity for ephedrine(0.05～10 μg/mL,r=0.999 8)and pseudoephedrine(0.02～5 μg/mL,r=0.999 5).Extraction recoveries ranged from 89.4％～95.8％(ephedrine)and 90.3％～93.8％(pseudoephedrine).Limits of detection and quantification of ephedrine and pseudoephedrine were 0.005 μg/mL and 0.01 μg/mL,the intra-day precision and accuracy were less than 5.87％and 9.56％,respectively,and the inter-day precision and accuracy were less than 7.54％and 9.27％,respectively.The stability of ephedrine and pseudoephedrine in urine in 15 d was good under the conditions of room temperature and-20 ℃.Conclusion The GC-MS/MS analytical method for the analysis of ephedrine and pseudoephedrine components in urine established in this study is accurate,stable and sensitive,which can provide data technical support for the forensic toxicological analysis of amphetamine-type drugs or new psychoactive substances in the cathinone group.

Objective:To analyze and summarize the operational mechanisms of the " National Facility for Translational Medicine (Shanghai)" (referred to as the Shanghai Facility), providing reference for the high-quality construction, management, and utilization of such facilities.Methods:Using the construction and operation of the Shanghai facility as a case study, this paper analyzed and discussed the facility's construction content, functional positioning, operational management systems, operational outcomes, in the meanwhile summarizing experience in construction and running of the facility.Results:Since the Shanghai facility was completed and officially put into operation in December 2020, significant achievements had been made in platform construction and operation.Conclusions:The successful operation of the Shanghai facility provides valuable experience for the construction of national major scientific and technological infrastructure in the field of translational medicine. In the future, its construction and management can be further improved through measures such as multi-channel fundraising, building-up of a multidisciplinary translational medicine talent team, and establishment of reasonable facility assessment criteria and talent evaluation standards.

Objective:To evaluate the effect of transnasal humidified rapid insufflation ventilatory exchange (THRIVE) on regional cerebral oxygen saturation (rScO 2) during induction of general anesthesia in patients undergoing traumatic brain injury (TBI) emergency surgery. Methods:A prospective randomized controlled trial was conducted. The TBI emergency general anesthesia patients who underwent intracranial hematoma removal surgery at the Northern Jiangsu People's Hospital from January to July in 2023 were enrolled. The patients were divided into a conventional mask ventilation group and a THRIVE group using a random number table method. The patients in the conventional mask ventilation group were anesthetized and induced to pre oxygenate without positive pressure ventilation in the front mask for 10 minutes, with an oxygen flow rate of 8 L/min and an fraction of inspired oxygen (FiO 2) of 1.00. After anesthesia induction for about 90 s, tracheal intubation was performed after the muscle relaxant took effect (patient's jaw muscle was relaxed). The patients in the THRIVE group were pre oxygenated with THRIVE for 10 minutes, with an oxygen flow rate of 30 L/min and a FiO 2 of 1.00. During anesthesia induction, the oxygen flow rate was increased to 50 L/min, and anesthesia induction medication was used. The lower jaw of patient was supported with both hands to maintain airway patency, and the patient's mouth was kept closed throughout the process. After the muscle relaxant took effect (the patient's jaw muscle was relaxed), tracheal intubation was performed. At the time of patient entering the operating room, 10 minutes of pre oxygenation, and immediately after successful intubation, rScO 2 was measured on the surgical and non-surgical sides. At the same time, ultrasound was used to measure the cross-sectional area (CSA) of the gastric antrum and arterial blood gas analysis was performed. The partial pressure of end-tidal carbon dioxide (P ETCO 2) during the first mechanical ventilation after successful tracheal intubation, the incidence of hypoxemia [pulse oxygen saturation (SpO 2) < 0.95] during tracheal intubation, as well as prognostic indicators such as the length of intensive care unit (ICU) stay, total length of hospital stay, and Glasgow outcome scale (GOS) score at discharge were recorded. Results:During the study period, a total of 70 TBI patients underwent emergency general anesthesia surgery, of which 2 patients died postoperatively, 2 patients were unable to cooperate with closed mouth breathing, and 3 patients had poor ultrasound image acquisition in the gastric antrum, all of whom were excluded. A total of 63 patients were ultimately enrolled, including 32 in the conventional mask ventilation group and 31 in the THRIVE group. There were no statistically significant differences in gender, age, body mass index (BMI), American Society of Anesthesiologists (ASA) classification, Glasgow coma scale (GCS) score, optic nerve sheath diameter (ONSD), baseline vital signs, fasting situation, anesthesia time, surgical time, and intraoperative blood loss between the patients in the two groups, indicating comparability. When entering the operating room, there was no statistically significant difference in rScO 2 on the surgical and non-surgical sides, and blood gas analysis indexes arterial partial pressure of oxygen (PaO 2) and arterial partial pressure of carbon dioxide (PaCO 2) between the patients in the two groups. When pre oxygenated for 10 minutes, both the surgical and non-surgical sides rScO 2 levels in the THRIVE group were significantly higher than those in the conventional mask ventilation group (surgical side: 0.709±0.036 vs. 0.636±0.028, non-surgical side: 0.791±0.016 vs. 0.712±0.027, both P < 0.01), and the PaO 2 was significantly increased [mmHg (1 mmHg≈0.133 kPa): 450.23±60.99 vs. 264.88±49.33, P < 0.01], PaCO 2 was significantly reduced (mmHg: 37.81±3.65 vs. 43.59±3.76, P < 0.01), and the advantage continues tilled immediately after successful intubation. There was no statistically significant difference in CSA at each time point of ultrasound examination between the two groups. Compared with the conventional mask ventilation group, the patients in the THRIVE group showed a significant decrease in P ETCO 2 during the first mechanical ventilation after successful tracheal intubation (mmHg: 43.10±2.66 vs. 49.22±3.31, P < 0.01), and the incidence of hypoxemia during tracheal intubation was also significantly reduced [0% (0/31) vs. 28.12% (9/32), P < 0.01]. In terms of prognostic indicators, there was no statistically significant difference in the length of ICU stay and total length of hospital stay between the patients in the conventional mask ventilation group and the THRIVE group [length of ICU stay (days): 10 (9, 10) vs. 10 (9, 11), total length of hospital stay (days): 28.00 (26.00, 28.75) vs. 28.00 (27.00, 29.00), both P > 0.05]. However, the proportion of patients in the THRIVE group with a good prognosis at discharge (GOS score > 3) was significantly higher than that in the conventional mask ventilation group [35.5% (11/31) vs. 12.5% (4/32), P < 0.05]. Conclusion:THRIVE can significantly increase rScO 2 during anesthesia induction in TBI emergency surgery patients and improve their neurological function prognosis.

Objective:To analyze the distribution of clopidogrel metabolism-related gene variability in Kawasaki disease (KD) children with coronary artery lesions (CAL) across different age groups and the impact of genetic variability on the efficacy of clopidogrel antiplatelet therapy.Methods:A retrospective cohort study was conducted. Clinical data were collected from 46 KD children with CAL who were hospitalized in the Cardiovascular Center of Children′s Hospital of Fudan University between January 2021 and August 2022 and were treated with clopidogrel, including gender, age, body mass index, course of KD, CAL severity grade, and baseline platelet count. According to their age, the children were divided into ≥2-year-old group and <2-year-old group. Their platelet responsiveness was assessed by adenosine diphosphate-induced platelet inhibition rate (ADPi) calculated via thromboelastography, and children were categorized into high on-treatment platelet reactivity (HTPR) and normal on-treatment platelet reactivity (NTPR) groups. Genotypes of CYP2C19, PON1 and ABCB1 were detected. The t test, one-way analysis of variance and Chi-square test were used for intergroup comparison. Results:Among the 46 KD children with CAL, 34 were male and 12 were female; 37 were ≥2-year-old and 9 were <2-year-old; 25 cases were in the HTPR group and 21 cases were in the NTPR group, with 19 HTPR and 18 NTPR in the ≥2-year-old group, and 6 HTPR and 3 NTPR in the <2-year-old group. Genetic analysis showed that 92 alleles among the 46 children, with frequencies of CYP2C19*1, CYP2C19*2, CYP2C19*3, CYP2C19*17, PON1 192Q, PON1 192R, ABCB1 3435C, ABCB1 3435T at 59% (54/92), 32% (29/92), 9% (8/92), 1% (1/92), 36% (36/92), 64% (59/92), 63% (58/92) and 37% (34/92), respectively. Analysis of the impact of genotype on ADPi revealed that in children aged ≥2 years, those with CYP2C19*1/*3 genotype had significantly lower ADPi than those with CYP2C19*1/*1 genotype ((34±15)% vs. (61±29)%, t=2.18, P=0.036). There were also no significant difference in ADPi among children with PON1 192Q homozygous, PON1 192R heterozygote and PON1 192R homozygous genotypes ((40±22)% vs. (52±33)% vs. (65±27)%, F=2.17, P=0.130), or among those with ABCB1 3435C homozygous, ABCB1 3435T heterozygote and ABCB1 3435T homozygous genotypes ((55±34)% vs. (60±27)% vs. (49±24)%, F=0.33, P=0.719). In <2-year-old group, there were no significant differences in ADPi across CYP2C19*1/*1, CYP2C19*1/*2 and CYP2C19*2*2 genotypes ((40±20)% vs. (53±37)% vs. (34±16)%, F=0.37, P>0.05). There were no significant differences in ADPi across CYP2C19*1/*1 and CYP2C19*1/*3 genotypes ((44±27)% vs. (42±20)%, t=0.08, P>0.05). There were no significant differences in ADPi across PON1 192Q homozygous, PON1 192R heterozygote and PON1 192R homozygous genotypes (45% vs. (55±27)% vs. (24±5)%, F=1.83, P>0.05). There were no significant differences in ADPi across ABCB1 3435C homozygous, ABCB1 3435T heterozygote and ABCB1 3435T homozygous genotypes ((36±16)% vs. (50±35)% vs. 45%, F=0.29, P>0.05). The risk analysis of HTPR in different genotypes revealed that in children aged ≥2 years, carrying at least 1 or 2 loss-of-function alleles of CYP2C19 was a risk factor for HTPR ( OR=4.69, 10.00, 95% CI 1.11-19.83, 0.84-119.32, P=0.033, 0.046, respectively), and PON1 192R homozygosity and carrying at least one PON1 192R allele were protective factors against HTPR ( OR=0.08, 0.13, 95% CI 0.01-0.86, 0.01-1.19, P=0.019, 0.043, respectively). Conclusion:KD children aged ≥2 years carrying CYP2C19 loss-of-function alleles and PON1 192Q are more likely to develop HTPR.

Objective:To investigate the role of TRIZ theory in clinical teaching in orthopedic operating room.Methods:A total of 43 interns in the orthopedic operating room of our hospital from October 2019 to July 2020 were selected as control group, and 46 interns in the orthopedic operating room of our hospital from August 2020 to May 2021 were selected as observation group. The interns in the control group received traditional teaching, and those in the observation group received teaching based on TRIZ theory. The two groups were compared in terms of professional assessment results, self-evaluation, satisfaction score, and qualification of aseptic operation in orthopedic operating room. SPSS 22.0 was used to perform the t-test and the chi-square test. Results:Compared with the control group, the observation group had significantly higher theoretical knowledge score, practical skill score, and weighted total score ( t=14.90, 11.82, and 13.23, all P?0.001). Compared with the control group, the observation group also had significantly higher scores of analysis and problem-solving ability, clinical thinking, doctor-patient communication, psychological quality, clinical case analysis, self-study ability, and teaching satisfaction ( t=7.88, 11.78, 15.26, 7.94, 12.93, 9.83, and 13.22, all P?0.001). Compared with the control group, the observation group had significantly higher qualified rates of surgical hand-washing, wearing sterile surgical gowns, non-contact glove wearing; and bacteriological testing ( χ 2=4.22, 6.02, 4.92, and 7.59, P=0.040, 0.014, 0.027, and 0.006). Conclusion:TRIZ theory has a certain value in clinical teaching in orthopedic operating room and can significantly improve the scores of theoretical knowledge and practical skills, strengthen aseptic operation abilities in orthopedic operating room, and enhance the satisfaction with teaching among interns.

Objective:To investigate the effects of continuous renal replacement therapy (CRRT) on plasma concentration, clinical efficacy and safety of colistin sulfate.Methods:Clinical data of patients received with colistin sulfate were retrospectively analyzed from our group's previous clinical registration study, which was a prospective, multicenter observation study on the efficacy and pharmacokinetic characteristics of colistin sulfate in patients with severe infection in intensive care unit (ICU). According to whether patients received blood purification treatment, they were divided into CRRT group and non-CRRT group. Baseline data (gender, age, whether complicated with diabetes, chronic nervous system disease, etc), general data (infection of pathogens and sites, steady-state trough concentration, steady-state peak concentration, clinical efficacy, 28-day all-cause mortality, etc) and adverse event (renal injury, nervous system, skin pigmentation, etc) were collected from the two groups.Results:A total of 90 patients were enrolled, including 22 patients in the CRRT group and 68 patients in the non-CRRT group. ① There was no significant difference in gender, age, basic diseases, liver function, infection of pathogens and sites, colistin sulfate dose between the two groups. Compared with the non-CRRT group, the acute physiology and chronic health evaluation Ⅱ (APACHE Ⅱ) and sequential organ failure assessment (SOFA) were higher in the CRRT group [APACHE Ⅱ: 21.77±8.26 vs. 18.01±6.34, P < 0.05; SOFA: 8.5 (7.8, 11.0) vs. 6.0 (4.0, 9.0), P < 0.01], serum creatinine level was higher [μmol/L: 162.0 (119.5, 210.5) vs. 72.0 (52.0, 117.0), P < 0.01]. ② Plasma concentration: there was no significant difference in steady-state trough concentration between CRRT group and non-CRRT group (mg/L: 0.58±0.30 vs. 0.64±0.25, P = 0.328), nor was there significant difference in steady-state peak concentration (mg/L: 1.02±0.37 vs. 1.18±0.45, P = 0.133). ③ Clinical efficacy: there was no significant difference in clinical response rate between CRRT group and non-CRRT group [68.2% (15/22) vs. 80.9% (55/68), P = 0.213]. ④ Safety: acute kidney injury occurred in 2 patients (2.9%) in the non-CRRT group. No obvious neurological symptoms and skin pigmentation were found in the two groups. Conclusions:CRRT had little effect on the elimination of colistin sulfate. Routine blood concentration monitoring (TDM) is warranted in patients received with CRRT.

The perception of motion is an important function of vision. Neural wiring diagrams for extracting directional information have been obtained by connectome reconstruction. Direction selectivity in Drosophila is thought to originate in T4/T5 neurons through integrating inputs with different temporal filtering properties. Through genetic screening based on synaptic distribution, we isolated a new type of TmY neuron, termed TmY-ds, that form reciprocal synaptic connections with T4/T5 neurons. Its neurites responded to grating motion along the four cardinal directions and showed a variety of direction selectivity. Intriguingly, its direction selectivity originated from temporal filtering neurons rather than T4/T5. Genetic silencing and activation experiments showed that TmY-ds neurons are functionally upstream of T4/T5. Our results suggest that direction selectivity is generated in a tripartite circuit formed among these three neurons-temporal filtering, TmY-ds, and T4/T5 neurons, in which TmY-ds plays a role in the enhancement of direction selectivity in T4/T5 neurons.
Animals ; Neurites ; Drosophila ; Neurons ; Connectome