ObjectiveThe aim of this study was to investigate the prophylactic effects of caloric restriction (CR) on lipopolysaccharide (LPS)-induced septic cardiomyopathy (SCM) and to elucidate the mechanisms underlying the cardioprotective actions of CR. This research aims to provide innovative strategies and theoretical support for the prevention of SCM. MethodsA total of forty-eight 8-week-old male C57BL/6 mice, weighing between 20-25 g, were randomly assigned to 4 distinct groups, each consisting of 12 mice. The groups were designated as follows: CON (control), LPS, CR, and CR+LPS. Prior to the initiation of the CR protocol, the CR and CR+LPS groups underwent a 2-week acclimatization period during which individual food consumption was measured. The initial week of CR intervention was set at 80% of the baseline intake, followed by a reduction to 60% for the subsequent 5 weeks. After 6-week CR intervention, all 4 groups received an intraperitoneal injection of either normal saline or LPS (10 mg/kg). Twelve hours post-injection, heart function was assessed, and subsequently, heart and blood samples were collected. Serum inflammatory markers were quantified using enzyme-linked immunosorbent assay (ELISA). The serum myocardial enzyme spectrum was analyzed using an automated biochemical instrument. Myocardial tissue sections underwent hematoxylin and eosin (HE) staining and immunofluorescence (IF) staining. Western blot analysis was used to detect the expression of protein in myocardial tissue, including inflammatory markers (TNF-α, IL-9, IL-18), oxidative stress markers (iNOS, SOD2), pro-apoptotic markers (Bax/Bcl-2 ratio, CASP3), and SIRT3/SIRT6. ResultsTwelve hours after LPS injection, there was a significant decrease in ejection fraction (EF) and fractional shortening (FS) ratios, along with a notable increase in left ventricular end-systolic diameter (LVESD). Morphological and serum indicators (AST, LDH, CK, and CK-MB) indicated that LPS injection could induce myocardial structural disorders and myocardial injury. Furthermore, 6-week CR effectively prevented the myocardial injury. LPS injection also significantly increased the circulating inflammatory levels (IL-1β, TNF-α) in mice. IF and Western blot analyses revealed that LPS injection significantly up-regulating the expression of inflammatory-related proteins (TNF-α, IL-9, IL-18), oxidative stress-related proteins (iNOS, SOD2) and apoptotic proteins (Bax/Bcl-2 ratio, CASP3) in myocardial tissue. 6-week CR intervention significantly reduced circulating inflammatory levels and downregulated the expression of inflammatory, oxidative stress-related proteins and pro-apoptotic level in myocardial tissue. Additionally, LPS injection significantly downregulated the expression of SIRT3 and SIRT6 proteins in myocardial tissue, and CR intervention could restore the expression of SIRT3 proteins. ConclusionA 6-week CR could prevent LPS-induced septic cardiomyopathy, including cardiac function decline, myocardial structural damage, inflammation, oxidative stress, and apoptosis. The mechanism may be associated with the regulation of SIRT3 expression in myocardial tissue.

Objective:To study the clinical characteristics of congenital esophageal atresia (CEA) and risk factors of mortality associated with esophageal repair (ER) surgery.Methods:From January 2010 to December 2022, patients diagnosed of CEA using chest and abdomen X-ray and esophagography in our hospital were retrospectively reviewed. The patients were assigned into ER group and non-ER group according to the treatments. The ER group was subgrouped into survival group and death group according to the prognosis. Clinical data and outcomes were collected and compared between the groups.Results:A total of 553 cases were enrolled. According to Gross classification, 29 patients (5.2%) were type A, 2 patients (0.4%) were type B, 504 patients (91.1%) were type C, 6 patients (1.1%) were type D and 11 patients (2.0%) were type E. One patient had simple transluminal septal atresia of the esophagus. 406 patients were in ER group and 147 in non-ER group. Compared with ER group, non-ER group had significantly higher incidences of preterm birth, low birth weight and overall malformations (all P<0.05). In ER group, 152 patients (37.4%) received open thoracic surgery (OTS), 243 (59.9%) had video-assisted thoracoscopic surgery (VATS) and 11 (2.7%) were VATS converted to OTS. Postoperative anastomotic leakage (PAL) occurred in 92 patients (22.7%) and 15 patients (3.7%) died after surgery. The median length of hospital stay was 23 (17, 36) d. Compared with the survival group, the death group had higher incidences of preterm birth, low birth weight, VATS converted to OTS, mechanical ventilation after ER, and shorter length of hospital stay (all P<0.05). After adjusted for birth weight, VATS converted to OTS ( OR=9.585, 95% CI 1.899-48.374) and mechanical ventilation after ER ( OR=7.821, 95% CI 1.002-61.057) were risk factors of mortality in ER patients. Conclusions:Non-ER patients have higher incidences of preterm birth, low birth weight and overall malformations than ER patients. VATS is the method of choice for CEA. Preterm birth, low birth weight, VATS converted to OTS and mechanical ventilation after ER are risk factors of mortality in ER patients.

Objective To design an experimental device for simulating the interface micro motion of bone trabecular prosthesis and carry out the finite element analysis.Methods The experimental device was composed of a screw-in cylinder with threads,a flexible hinge,a micro-motion rod,a trabecular prosthesis,a connecting rod and a fixation post.A model of the experimental device was constructed with SolidWorks software,and then imported into ABAQUS software to establish a finite element model.An axial displacement load was applied to the femur to analyze the effects of the position of the flexible hinge,the gap between the prosthesis and the femur and the length of the connecting rod on the micro motion.Results The interface micro motion produced by the experimental device increased with the distance of the flexible hinge from the lower end of the screwed-in cylinder;the gap between the prosthesis and the femur did not affect the interface micro motion when the gap was not lower than 20 μm;the interface micro motion rose with the length of the connecting rod.Conclusion The experimental device can accurately simulate the micro motion of different bone trabecular prosthesis interfaces,and can be used for studying the effect of the interface micro motion on osseointegration.[Chinese Medical Equipment Journal,2024,45(1):25-30]

Objective To analyze the antigen recognition sites of commercial and homemade antibodies against aquaporin(AQP)9,and to identify the application effect.Methods Western blotting was used to compare the efficacy of three commercial antibodies and self-made antibody in identifying AQP9 genotypes.The antigen recognition sites of four antibodies and their specificities in practical applications were analyzed.Results Western blotting showed that protein bands of three commercial antibodies were detected in both WT and Aqp9-/-mice.The keyhole limpet hemocyanin(KLH)conjugated synthetic peptides corresponding to the three commercial antibodies were derived from rat,human and human,respectively.And The sequences of these three synthetic peptides were different from those of mice.AQP3/7 and AQP9 have similar molecular weight and were expressed in the liver with high homology.An obvious band of self-made antibody was observed at the 27 kD position in WT mice,but no band was observed at the corresponding position in Aqp9-/-mice.Conclusion Commercial antibodies 1 and 3 can be used to assist in the identification of genotypes in Aqp9-/-mice.Homemade antibodies can accurately identify genotypes at the protein level.

Objective To observe the effect of parecoxib sodium combined with dexmedetomidine preemptive analgesia on postoperative analgesia in patients with modified radical mastectomy for breast cancer.Methods Patients who underwent modified radical mastectomy for breast cancer were randomly divided into control group and treatment group based on simple binary randomization by random number table method.In the control group,"0.05 mg·kg-1 midazolam+1.0-1.5 mg·kg-1 propofol+0.4 μg·kg-1sufentanil citrate+0.15 mg·kg-1 phenylsulfonyl cisatracurium"was used for induction and maintenance of anesthesia.In the treatment group,the induction and maintenance of anesthesia was performed with the protocol of"parecoxib sodium 40 mg+dexmedetomidine 0.5 μg·kg-1·h-1)continuous pumping"on the basis of control group,and mechanical ventilation was performed by tracheal intubation 5 min after induction.The effect of pre-analgesia,postoperative sedation,hemodynamic indexes,surgical improvement indexes and application safety were observed by groups.Results There were 46 patients in each group.Pain visual analogue scores at 6,12 and 24 h in treatment group were 2.09±0.72,4.17±1.07 and 4.07±1.05,lower than those in control group,which were 2.61±1.03,4.76±1.27 and 4.65±1.11,the differences were statistically significant(all P＜0.05).The Ramsay sedation scores of the treatment group and the control group at 6 h after surgery were(2.85±0.62)and(2.11±0.73)points,respectively;the sedation scores of Ramsay at 12 h were 1.41±0.28 and 1.06±0.15,respectively.At 24 h,the sedation scores of Ramsay were 1.15±0.18 and 0.64±0.13,respectively,and the difference was statistically significant(P＜0.05).HR and MAP of treatment group and control group at T2 and T3 were significantly lower than those at T1 and T0(P＜0.05),there were no difference in HR and MAP between treatment group and control group at T2 and T3(P＜0.05).Operation time,recovery time after operation and intraoperative blood loss in treatment group were significantly lower than those in control group,and the differences were statistically significant(all P＜0.05).The success rate of 12-hour postoperative analgesia in test group and control group was 82.61％(38 cases/46 cases)and 63.04％(29 cases/46 cases),respectively,and the difference was statistically significant(P＜0.05).The adverse drug reactions in treament group and control group mainly included bradycardia,headache,dizziness and nausea,and the incidence of adverse drug reactions in treatment group and control group were 13.04％(6 cases/46 cases)and 8.70％(4 cases/46 cases),respectively,the difference was no statistically significant(P＜0.05).Conclusion Parecoxib sodium combined with dexmedetomidine preemptive analgesia has significantly improved analgesia and sedative effects in modified radical mastectomy for breast cancer,can prolong sedation and analgesia time,and stably control the perioperative hemodynamics of patients.

Conducting local tolerance testing on parentaral drugs is of great significance for evaluating the clinical medication risks of drugs.Although relevant domestic and international guidelines provide detailed instructions on how to conduct local tolerance testing,it was found that some products still provide non-standard application materials,which affects the efficiency of drug development.This article summarizes the information on domestic and international guidance related to the local tolerance testing and elaborates on common problems based on specific application cases,with the aim of of providing reference for related work.

Objective To investigate the effects of remifentanil and dexmedetomidine controlled hypotension on coagulation function,cerebral oxygen metabolism and amino acid neurotransmitter levels in elderly patients undergoing orthopedic surgery.Methods The elderly patients who underwent lower extremity orthopedic surgery were divided into group A(given dexmedetomidine for hypotension),group B(given remifentanil for hypotension)and group C(given remifentanil combined with dexmedetomidine for hypotension)according to different anesthetic drugs.Systolic blood pressure(SBP),diastolic blood pressure(DBP)and heart rate(HR)were compared among the 3 groups.Cerebral oxygen metabolism[arterial oxygen content,(CaO2),oxygen saturation of internal jugular vein(SjvO2),oxygen content of internal jugular vein(CjvO2)],coagulation function[activated partial thromboplastin time(APTT),prothrombin time(PT),thrombin time(TT),plasma fibrinogen(FIB)],amino acid neurotransmitters[glutamic acid(Glu),aspartate(Asp),gamma-aminobutyric acid(GABA)]were compared,and the occurrence of adverse drug reactions during the trial were compared.Results At 12 h after anesthesia,the APTT of group A,group B and group C were(17.26±2.77),(17.37±2.92)and(31.11±4.74)s,respectively.GABA were(18.74±2.71),(19.22±2.60)and(23.37±2.59)mmol·L-1,respectively.3 min after withdrawal,CaO2 in group A,group B and group C were(139.31±9.03),(140.90±8.70)and(131.75±10.11)mL·L-1,respectively;SjvO2 were(63.59±2.23)％,(63.40±2.44)％and(68.82±3.36)％,respectively.The above indexes of group C were compared with those of group A and group B,and the differences were statistically significant(all P＜0.05).The incidence of adverse drug reactions in group A,B and C were 12.82％,27.50％and 7.32％,respectively.The incidence of adverse drug reactions in group C were lower than that in group A and group B(P＜0.05).Conclusion Remifentanil combined with dexmedetomidine for controlled hypotension in elderly orthopedic surgery has better blood pressure control effect,can improve postoperative coagulation function,maintain cerebral oxygen metabolism balance,reduce cognitive function injury and anesthesia adverse drug reactions.

Objective To study the pharmacokinetic and pharmacodynamic characteristics of compound levodopa/carbidopa(250 mg/25 mg)and levodopa/benserazide(200 mg/50 mg)in patients with Parkinson's disease(PD).Methods This experiment used a levodopa challenge test with a randomized crossover design.In the first week,20 PD patients orally received either 275 mg of compound levodopa/carbidopa or 250 mg of levodopa/benserazide on an empty stomach,and in the second week,they received the other treatment.The levodopa blood concentration was measured using high-performance liquid chromatography-tandem mass spectrometry,and motor symptoms were evaluated using the Movement Disorder Society-Unified Parkinson's Disease Rating Scale Ⅲ.Results Data from 17 patients in the compound levodopa/carbidopa group and 18 patients in the levodopa/benserazide group was included in the analysis.After administration,the Cmax values of compound levodopa/carbidopa and levodopa/benserazide groups were(3 563.76±1 003.06)and(3 642.44±1 192.70)ng·mL-1;the tmax values were(1.10±0.44)and(1.03±0.55)h;the t1/2 values were(1.52±0.15)and(1.68±0.27)h;the AUC0-t values were(7 625.19±1 706.85)and(5 846.07±1 191.16)ng·mL-1·h;the mean residence time(MRT)values were(2.39±0.361)and(2.14±0.37)h,respectively.There were no statistically significant differences in the Cmax,tmax,and t1/2 values between the two groups(all P＞0.05).Compared with the levodopa/benserazide group,the compound levodopa/carbidopa group increased levodopa AUC and prolonged MRT(all P＜0.05).The improvement in motor symptoms and levodopa blood concentration showed consistent trends at various time points in both groups.The compound levodopa/carbidopa group showed significantly better improvement in motor function at 6 and 8 hours after medication compared to the levodopa/benserazide group[(-10.82±8.91)points vs(-5.17±6.78)points,(-7.88±10.05)points vs(-2.11±4.84)points;both P＜0.05].Conclusion The pharmacokinetic and pharmacodynamic characteristics of compound levodopa/carbidopa are similar to those of levodopa/benserazide.

Objective To investigate the distribution characteristics of pathogens in adult community-acquired pneumonia(CAP)patients who visited the fever clinic before and after the outbreak of the novel coronavirus infection,and to provide theoretical basis for the diagnosis,treatment,and prevention of CAP.Methods CAP patients who visited the fever clinic of Peking University Third Hospital from June 2017 to July 2022 were included in the study and divided into pre-outbreak and post-outbreak groups based on the time point(January 24,2020,when Beijing entered the first-level COVID-19 prevention and control).Respiratory samples were collected and pathogen nucleic acid detection was performed using real-time fluorescence quantitative polymerase chain reaction.The detection and distribution of pathogens were analyzed.Results A total of 415 CAP patients were included,divided into pre-outbreak group(312 cases)and post-outbreak group(103 cases).Mycoplasma pneumoniae,Streptococcus pneumoniae,and Influenza A virus were the three most common pathogens in the pre-outbreak CAP group.In the post-outbreak community-acquired pneumonia,Influenza B virus,Klebsiella pneumoniae and Streptococcus pneumoniae were the three most common pathogens.The incidence of Influenza A virus,Parainflluenza virus,and Mycoplasma pneumoniae was significantly higher in the pre-outbreak period than in the post-outbreak period,and the differences between the two groups were statistically significant(all P＜0.05).Conclusion Before and after the epidemic,viral infection are the main pathogens of CAP patients,which is of great significance for future empirical treatment,protection of susceptible population and control of infectious diseases.

AIM To investigate the effects of Zhuangyao Shuanglu Tongnao Formula on neuronal apoptosis in rats with cerebral ischemia-reperfusion injury based on the study of oxidative stress and inflammatory response.METHODS The rats were randomly divided into the sham operation group,the model group,the edaravone group(3.0 mg/kg),the low,medium and high dose groups(9.0,18.0,36.0 g/kg)of Zhuangyao Shuanglu Tongnao Formula,with 18 rats in each group.The middle cerebral artery occlusion/reperfusion was conducted by thread embolism method to simulate cerebral ischemia reperfusion injury in rats followed by 6 days corresponding drugs administration.Subsequently,the rats had their neurological function deficit scored by Zeal Longa scoring method;their sizes of cerebral infarction areas measured by TTC staining;their pathological damage and apoptosis of neurons in hippocampal CA1 area of ischemic penumbra of the brain tissue detected by HE staining and TUNEL staining;their SOD activity and levels of GSH,MDA,IL-6,IL-1β,TNF-α in brain tissue detected by kits;and their protein expressions of Bax,Bcl-2,caspase-3,cleaved-capase-3,TLR4,NF-κB p65,Nrf2,HO-1 in rat brain tissue determined by Western blot.RESULTS Compared with the model group,the groups intervened with edaravone,medium and high dose of Zhuangyao Shuanglu Tongnao Formula displayed improvements in the scores of nerve function defects,the rate of cerebral infarction,the rate of neuronal apoptosis,the levels of IL-6,IL-1β,TNF-α and MDA in the ischemic penumbra of brain tissues,the protein expressions of Bax and TLR4,the ratio of cleaved-capase-3/caspase-3 and p-NF-κB p65/NF-κB p65(P＜0.05),the levels of GSH,the activity of SOD and the protein expressions of Bcl-2,Nrf2 and HO-1(P＜0.05).CONCLUSION Being an inhibitor of oxidative stress and inflammatory response,Zhuangyao Shuanglu Tongnao Formula can alleviate brain injury in rats with cerebral ischemia reperfusion injury through the inhibition of neuronal apoptosis and improvement of neural function mediated by the inhibition of TLR4/NF-κB signal pathway and activation of Nrf2/HO-1 signal pathway.