OBJECTIVE To explore kinetic features and its underlying mechanism of the positive inotropic effect of liguzinediol(LZDO)in rats. METHODS ①An In vivo study was made to record the effect of LZDO 20 mg · kg-1 injected for 30 consecutive min from the left external jugular vein on pressure-volume relationships. ②Ex vivo study was used to record the antagonistic effect of LZDO on reduced contractility induced by caffeine. Caffeine and LZDO were perfused as follows:normal perfusion solution, caffeine 0.5 mmol · L-1,and then caffeine 0.5 mmol · L-1+LZDO 100 μmol · L-1. ③ Ca2+ transient from cardiomyocyte sarcoplasmic reticulum (SR) was measured to analyze the effect of LZDO on Ca2 +release blocked by thapsigargin. Thapsigargin and LZDO were perfused as follows:normal perfusion solution,thapsigargin 2 μmol · L-1,and then thapsigargin 2 μmol · L-1+LZDO 100 μmol · L-1.④The SR vesicles were prepared and the effect of LZDO(1,10 and 100μmol·L-1)on sarcoplasmic reticulum Ca2+ATPase(SERCA2a)activity was determined according to the ultramicro-Ca2+-ATP enzyme kit. RESULTS ① LZDO 20 mg · kg- 1 significantly reduced the end-systolic volume (Ves) and enhanced the end-systolic pressure (Pes),stroke volume (SV),ejection fraction (EF),cardiac output(CO),peak rate of rise of left ventricular pressure(+dp/dtmax)and stroke work(SW)(P<0.05). However,LZDO 20 mg · kg-1 did not significantly change the heart rate(HR )or the end-diastolic volume (Ved). ② Caffeine 0.5 mmol · L- 1 significantly enhanced HR,left ventricular developed pressure (LVDP ),and+dp∶dtmax at 5 min after caffeine and decreased at 30 min. However,LZDO 100μmol·L-1 restored the reduced HR,LVDP,and+dp/dtmax induced by caffeine at 30 min(P<0.05).③Thapsigargin 2μmol·L-1 significantly reduced the SR Ca2+transient from perfusion solution group(100±5)%to(51± 5)%(P<0.05) and LZDO 100 μmol · L-1 failed to restore the decreased Ca2+ transient〔(49 ± 4)%〕. Normalized Ca2+transients were reduced by thapsigargin 2μmol·L-1 and thapsigargin 2μmol·L-1+LZDO 100 μmol · L-1. ④ LZDO(10 and 100 μmol · L-1)significantly increased the activities of SERCA2a in perfusion solution group 0.98±0.10 to 1.17±0.20 and (1.43±0.09)μmol Pi·g-1·h-1,respectively(P<0.05). CONCLUSION LZDO can enhance SR Ca2+ gradient by activating the SERCA2a and might be developed to serve as a potential positive inotropic agent in clinical settings.

OBJECTIVE To explore potential proarrhythmic effect and underlying mechanism of azithromycin (AZM) and Shengmai injection (SM) used clinically.METHODS ① In vivo guinea pig ECG recordings were made to analyze effects of jugular intravenous(iv) injection of AZM [38.2 mg· kg-1,one time (clinically relevant dose,CRD)],or SM (4.6 mL· kg-1,one time CRD) or their combination.②In vitro ECG recordings were made to analyze effects of AZM,SM or AZM + SM on ECG in isolated hearts of guinea pigs.AZM [one,five and ten times (clinically relevant concentrations,CRC)] was perfused in this order:41.5 →207.5 → 415 mg· L-1 and SM (one,five and ten times CRC) in this order:5 →25 →50 mL· L-1.Also,AZM (41.5 mg· L-1,one time CRC) +SM (5 mL· L-1,one time CRC) was perfused to isolated hearts of guinea pigs.③ Enzymatically isolated cardiomyocytes from guinea pig left ventricles were perfused in this order:AZM 41.5 mg· L-1 →AZM 41.5 mg· L-1+SM 5 mL· L-1 for action potential,L-type Ca2+ and Na+ current recordings,respectively.RESULTS ① Neither AZM 38.2 mg· kg-1,nor SM 4.6 mL· kg-1 significantly changed the in vivo ECG.However,AZM 38.2 mg· kg-1 +SM 4.6 mL · kg-1 significantly reduced heart rate (P＜0.05) and prolonged the P-R (P＜0.05) and QRS (P＜0.05) intervals.②AZM 41.5,207.5 and 415 mg· L-1 reduced heart rate (P＜0.05) and prolonged the P-R (P＜0.05) and QRS (P＜0.05) intervals in a concentration-dependent manner.AZM 415 mg·L-1 also prolonged QTc (P＜0.05) interval.SM 5,25 and 50 mL· L-1 reduced heart rate (P＜0.05) and prolonged the P-R interval (P＜0.05) in a concentration-dependent manner.SM had no effect on QRS or QTc intervals.Washout partially recovered the above changes.Moreover,AZM 41.5 mg· L-1 + SM 5 mg·L-1 significantly reduced heart rate (P＜0.05) and prolonged the P-R (P＜0.05) and QRS intervals.③ AZM 41.5 mg·L-1 did not significantly change the action potential amplitude (APA),action potential durations at 50％ (APD50) and 90％ (APD90) repolarization levels,or L-type Ca2+ and Na+ currents.However,AZM+SM 5 mg· L-1 significantly reduced APA (P＜0.05),shortened APD50 (P＜0.05) and APD90 (P＜0.05) and inhibited the L-type Ca2+ (P＜0.05) and Na+ (P＜0.05) currents.CONCLUSION AZM and SM has potential prorrhythmic risks.The combined use might cause higher risk of arrhythmia.The underlying mechanism for proarrhythmia is mediated by inhibition of the L-type Ca2+ and Na+ currents.

Objective:To investigate the therapeutic effect of conjoint fascia sheath suspension and levator palpebrae muscle shortening on congenital severe blepharoptosis.Methods:From June 2014 to December 2018, 30 cases (40 eyes) of congenital severe ptosis were treated in Ningbo First Hospital and Shaoxing Women and Children＇s Hospital. All patients were corrected by conjoint fascia sheath suspension and levator palpebrae muscle shortening. Six months after operation, the distance between the middle point of upper eyelid margin and corneal reflex point was measured to evaluate the correction effect of blepharoptosis; the improvement of upper eyelid appearance was evaluated by 5-point Likert scale (LS), and the incidence of complications was counted.Results:Thirty patients (40 eyes) were followed up for 6-12 months. Correction effect showed that preoperative marginal reflex distance (MRD) was (0.10±0.05) and postoperative MRD was (3.80±0.55); the difference was statistically significant ( t=0.95, P<0.05); 38 eyes (95%) were corrected and 2 eyes (5%) were undercorrected; appearance of upper eyelid showed that preoperative LS was (0.50±0.05) and postoperative LS (3.80±0.55); the difference was statistically significant ( t=0.98, P<0.05). Only one case was complicated with keratitis caused by improper early nursing after incomplete closure exposure, and the patient was cured by sealing the eyes combined with drug conservative treatment. Conclusions:Combined conjoint fascial sheath suspension and levator palpebrae shortening in the treatment of severe blepharoptosis has significant effect, with the advantages of simple operation, small surgical trauma, low recurrence rate, low incidence of complications, high predictability of surgical results and high satisfactory rate of patients.

Kidney transplantation is the most fundamental treatment for patients with end-stage renal disease. However, due to the long-term malnutrition of the patient before transplantation, coupled with the use of stress stimulation, immunosuppressive agents, and high-dose hormones after kidney transplantation, the patient is in a hypermetabolic state, and malnutrition is aggravated. The nutrition status of patients has a significant impact on the prognosis and development of kidney transplantation. Therefore, this article reviews the current status of nutrition intervention, the assessment of malnutrition, the related factors of malnutrition, and nutrition management in kidney transplantation recipients, so as to provide a reference for the nutrition and diet management of kidney transplantation recipients.

Objective To investigate the effect of basic fibroblast growth factor (bFGF) on autophagy of nerve cells in rats after traumatic brain injury (TBI).Methods A total of 120 healthy adult male SD rats were randomly divided into sham group,TBI + vehicle group,and TBI + bFGF group by random number table method,with 40 rats in each group.PinPointTM Precision Cortical Impactor was used to simulate the pathological damage after TBI.In the sham group,the dura was exposed without impact.In the TBI + bFGF group,250 μg/kg of human recombinant bFGF was given in the nasal cavity 1 hour before the modeling,while in the sham group and TBI + Vehicle group,the same amount of saline was given in the nasal cavity 1 hour before the modeling.The necrotic cells were observed by propidium iodide(PI) staining 6 hours after injury.The effect of bFGF on the nerve function after TBI in rats was evaluated with modified neurological severity score (mNSS) 24 hours after injury.The water content of brain tissue was measured by dry and wet method 48 hours after injury.The ratio of Beclin-1,P62 protein and microtubule-associated protein 1 light 3 (LC3)-Ⅱ/Ⅰ protein was detected by western blot.The volume of brain injury was calculated by integral method of brain tissue section.The positive neuron specific nuclear protein (NeuN) cells were observed by immunofluorescence staining.The apoptotic cells were observed by TUNEL.Results Compared with the sham group [(4.0 ± 1.2) ％],the percentage of necrotic cells in TBI + vehicle group [(54.3 ± 10.1) ％] and TBI + bFGF group [(34.5 ± 10.5) ％] increased significantly (P ＜ 0.05),but the percentage of necrotic cells in TBI + bFGF group increased less than that in TBI + vehicle group (P ＜ 0.05).Compared with the sham group [(0.3 ± 0.5)points],the mNSS in the TBI + vehicle group [(5.8 ±0.8)points] and TBI + bFGF group [(4.7 ± 1.1) points] were significantly increased (P ＜ 0.05),but the mNSS of TBI + bFGF group was lower than that of TBI + vehicle group (P ＜ 0.05).Compared with the sham group [(76.7 ± 0.7) ％],the water content of brain tissue of TBI + vehicle group [(79.2 ± 0.5) ％] and TBI + bFGF group [(78.4 ± 1.0) ％] were significantly increased (P ＜0.05),but the water content of TBI + bFGF group was significantly lower than that of TBI + vehicle group (P ＜0.05).Compared with the sham group,protein expression of Beclin-1 and LC3-I/Ⅰ in TBI + vehicle group and TBI +bFGF group were significantly improved (P ＜ 0.05),P62 protein expression was significantly decreased (P ＜ 0.05),the volume of brain tissue injury was significantly increased (P ＜ 0.05),the number of positive NeuN cells increased significantly (P ＜ 0.05),and the number of apoptotic cells and apoptotic cells were significantly increased (P ＜0.05).Compared with the TBI + Vehicle group,the up-regulation of Beclin-1 protein and LC3-Ⅱ/Ⅰ protein ratio was obviously inhibited in the TBI + bFGF group (P ＜ 0.05),the down-regulation of P62 protien was significantly suppressed,the volume of brain tissue injury was significantly decreased,and the number of positive NeuN cells and apoptotic cells was significantly reduced (P ＜ 0.05).Conclusion The bFGF can significantly inhibit excessive autophagy in rats after TBI,reduce brain edema,reduce cell apoptosis and necrosis,and improve neural function.

Objective:To explore the association between weight status and early changes in blood pressure, cardiac structure and function in children at 4 years of age.Methods:A cross-sectional study of the relationship between weight status and cardiovascular parameters was performed on the platform of "Shanghai Birth Cohort" in Shanghai Xinhua Hospital between 2017 and 2020. Height, weight, blood pressure and echocardiography were measured in 1 477 children at 4 years of age. According to body mass index (BMI), participants were classified into five groups: underweight, lean, normal weight, overweight and obese. Blood pressure, cardiac structure and function indexes were compared among different groups using one-way ANOVA. The associations between blood pressure, cardiac structure and function and weight status in children were analyzed by linear regression models. Multivariate logistic regression models were used to analyze whether weight status was an independent risk factor for elevated blood pressure or left ventricular hypertrophy (LVH) in children.Results:A total of 1 477 children including 772 boys and 705 girls were included in this study. There were 115 overweight and obese boys (14.9%) and 68 overweight and obese girls (9.6%). The majority of children had normal weight (916 cases, 62.0%), followed by underweight (303 cases, 20.5%), overweight (130 cases, 8.8%), lean (75 cases, 5.1%), and obese (53 cases, 3.6%). With the increase of BMI, systolic blood pressure, diastolic blood pressure, left ventricular mass index (LVMI), left ventricular posterior wall thickness in systole, left ventricular posterior wall thickness in diastole, left ventricular diameter in end-systole, left ventricular diameter in end-diastole, interventricular septum thickness in systole and left ventricular ejection fraction showed significantly positive trend, and the differences among the groups were significant (F=31.73, 6.59, 14.22, 4.96, 3.01, 31.50, 39.79, 5.91, 3.09, all P<0.05). Multiple linear regression showed that overweight and obese were all positively associated with systolic blood pressure (β=5.2, 95% CI 3.6-6.8), LVMI (β=1.9, 95% CI 0.8-3.1), left ventricular diameter in end-systole (β=1.3, 95% CI 0.9-1.8), and left ventricular diameter in end-diastole (β=1.6, 95% CI 1.0-2.2). In the Logistic regression model, compared with normal weight children, overweight ( OR=2.37, 95% CI 1.37-4.41) and obese children ( OR=10.90, 95% CI 4.47-26.60) both had significantly increased risk of elevated blood pressure. However, the risk of LVH did not significantly increased. Conclusions:Overweight and obesity in 4-year-old children are associated with increased blood pressure, increased left ventricle diameter and LVMI. Overweight and obesity are independent risk factors for elevated blood pressure in children at 4 years of age.

OBJECTIVE To mine the adverse drug event （ADE） signals of selinexor， and to provide reference for its clinical safety medication. METHODS ADE data for selinexor reported from July 3rd， 2019 to March 31st， 2023 were collected from the FDA adverse event reporting system （FAERS）. Data mining was performed by using the reporting odds ratio （ROR） and proportional reporting ratio （PRR） methods， and categorization statistics were performed by using the system organ class （SOC） and preferred term （PT） from drug ADE terminology set in the MedDRA （version 26.0）. RESULTS A total of 3 084 ADE reports were obtained for selinexor， with a total of 134 ADE-positive signals. Among the reported genders， there were 127 males and 124 females， with a predominant age of ≥65 years old （4.12%）； the United States had the highest number of reports （96.53%）， with consumers being the main reporters （77.27%）； severe ADR was mainly characterized by hospitalization/prolonged hospitalization （26.26%）， followed by death （17.15%）. The top 3 ADE in the list of frequency were nausea （1 162 times）， fatigue （790 times） and anorexia （610 times）， all of which were mentioned in the selinexor’s instructions. The top 3 signals in the list of strength were device-associated bacteremia （ROR＝115.07， PRR＝114.94）， blepharospasm dysfunction （ROR＝106.70， PRR＝106.54）， and salmonella sepsis （ROR＝99.90， PRR＝99.81）， all of which were not mentioned in the selinexor’s instructions. CONCLUSIONS In addition to the ADE of nausea mentioned in the instruction manual， attention should also paid to device-associated bacteremia， blepharospasm dysfunction， salmonella sepsis， and other ADE not mentioned in the instruction manual when using selinexor in clinical practice； weekly rechecking of the patient’s blood routine should be done to monitor the patient’s blood indexes， symptoms of infection， and so on， to ensure that the safety of 1661962346@qq.com drug use.

OBJECTIVE：To provide technical met hods for marketing authorization holder （MAH）to effectively use the data of adverse drug reaction （ADR），actively monitor and control the production quality risk ，and carry out drug production risk management. METHODS ：Through establishing three-dimensional risk matrix and risk trend model ，the risk early warning system of MAH production line based on ADR report data is designed and developed ；the main functions of the system were applied and analyzed according to the actual ADR report data of a certain company. RESULTS ：MAH production line risk warning system was established preliminarily. The main framework included data source and and processing module ，model construction module （three-dimensional matrix model included possibility index ，severity index and sensitivity index ，risk trend model was set according to the principle of product production batch number preparation ），and result output & analysis module. Five major functional modules included system configuratio ，production line signal detection ，visual statistical early warning ，ADR report management and standard data management. The application and analysis of ADR report data of a certain company showed that the system could realize detection and warning of the company ’s production line risk ，which intuitively reflected its high-risk production lines ，varieties and batch numbers. It was consistent wit h the actual safety sit uation of the company ’s varieties. CONCLUSIONS：The system can help MAH make use of ADR report data to actively monitor drug production quality risks in a timely manner ，investigate risk factors for high-risk production lines ， high-risk varieties and high-risk batch numbers，and assist in decision-making on the direction of risk investigation.

Female ; Humans ; Middle Aged ; Propofol ; therapeutic use ; Pulmonary Embolism ; complications ; Ventricular Fibrillation ; drug therapy ; etiology