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.

ObjectiveFat infiltration has been shown to be closely related to muscle mass loss and a variety of muscle diseases. This study proposes a method based on phase-angle electrical impedance tomography (ΦEIT) to visualize the electrical characteristic response caused by muscle fat infiltration, aiming to provide a new technical means for early non-invasive detection of muscle mass deterioration. MethodsThis study was divided into two parts. First, a laboratory pork model was constructed to simulate different degrees of fat infiltration by injecting1 ml or 2 ml of emulsified fat solution into different muscle compartments, and the phase angle images were reconstructed using ΦEIT. Second, a human experiment was conducted to recruit healthy subjects (n=8) from two age groups (20-25 years old and 26-30 years old). The fat content percentage η_fat of the left and right legs was measured by bioelectrical impedance analysis (BIA), and the phase angle images of the left and right calves were reconstructed using ΦEIT. The relationship between the global average phase angle Φ_M and the spatial average phase angle Φ_Mi of each muscle compartment and fat infiltration was further analyzed. ResultsIn the laboratory pork model, the grayscale value of the image increased with the increase of η_fat and Φ_M showed a downward trend. The results of human experiments showed that at the same fat content percentage, the Φ_M of the 26-30-year-old group was about 20%-35% lower than that of the 20-25-year-old group. The fat content percentage was significantly negatively correlated with Φ_M. In addition, the M₂ (soleus) compartment was most sensitive to fat infiltration, and the spatial average phase angles of the M₂ (soleus), M₃ (tibialis posterior and flexor digitorum longus), and M₄ (tibialis anterior, extensor digitorum longus, and peroneus longus) compartments all showed significant inter-group differences. ConclusionΦEIT imaging can effectively distinguish different degrees of fat infiltration, especially in deep, small or specially located muscles, showing high sensitivity, demonstrating the potential application of this method in local muscle mass monitoring and early non-invasive diagnosis.

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.

Objective To establish a rapid and convenient UPLC-MS/MS method for the determination of tamoxifen and its active metabolite endoxifen in plasma of patients with breast cancer.Methods With diazepam as the internal standard,the plasma sample was precipitated with acetonitrile and methanol-acetonitrile was used as mobile phase.The samples were separated by chromatographic column ZORBAX Eclipse plus C18(18 μm,2.1 mm x50 mm)and scanned by electrospray ion source and positive ion multiple reaction monitoring mode.The ion channels were detected as tamoxifen m/z 372.0→72.1,endoxifen m/z 374.0→58.2 and diazepam m/z 285→192.9.Results The linearity of tamoxifen and endoxifen were good in the concentration range of 1-500 ng·mL-1(R2=0.999 5)and 0.5-250 ng·mL-1,respectively(R2=0.999 9).The intra-day and inter-day precision of low,medium and high quality control concentrations were all less than 10％.Tamoxifen and endoxifen were stable at low temperature and stable after repeated freeze-thaw.Conclusion The experimental results show that the method meets the requirements of biological sample analysis,and the sample treatment is simple,specific,and can be used for the accurate and rapid determination of tamoxifen and indoloxifen in human plasma.

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.

Objective To explore the role of exosomes secreted by induced pluripotent stem cells(iPSC)in promoting the proliferation,invasion and migration of keratinocytes,thereby facilitating wound healing.Methods Extract iPSC-Exos and identify them through transmission electron microscopy,nanoparticle tracking analysis technology,and Western blotting.Purified iPSC-Exos labeled with PKH26 were added to keratinocytes(HaCaT)for the determination of keratinocyte uptake of exosomes.The optimal working concentration of exosomes was assessed using cell counting kit-8(CCK-8),and cells were divided into control group(cell scratch),and experimental group(cell scratch followed by addition of exosomes at the optimal working concentration).Proliferation,migration,and invasion abilities of cells in each group were evaluated using CCK-8,5-ethynyl-2'-deoxyuridine(EdU),scratch assay,and Transwell assay.Results iPSC-Exos exhibit a membranous vesicular structure with a round or elliptical shape,and their diameter is(120.00±25.00)nm.The expression of characteristic surface markers CD9,CD63,and CD81 on iPSC-Exos is positive in the experimental group,while being negative in the control group.HaCaT cells are capable of internalizing iPSC-Exos.After 24 hours of intervention,the scratch healing rates in the control and experimental groups are(25.70±1.07)％and(71.60±12.76)％,respectively.The Transwell invasion cell numbers are(86.33±10.79)and(166.33±24.13)in the control and experimental groups,and the EdU-positive proportions are(45.30±3.17)％and(78.10±6.29)％,respectively.The above indicators in the experimental group show statistically significant differences compared to the control group(all P＜0.05).Conclusion The exosomes secreted by pluripotent stem cells can promote the proliferation,migration,and invasion of keratinocytes,thereby indirectly promoting wound healing.

Objective To comprehensively evaluate the current situation of traditional Chinese medicine resource allocation in grassroots community health service centers in Guangzhou in 2022.Methods Based on the index system of traditional Chinese medicine resource allocation(community health service center)in Guangzhou,MATLAB R2021a and SPSS 27 software were used to comprehensively evaluate the current situation of traditional Chinese medicine resource allocation in 116 community health service centers in Guangzhou by TOPSIS method and RSR method.Results The allocation of TCM resources in 5 communities,including Xiaoguwei Street Community Health Service Center in Panyu District,Guangzhou City,Dadong Street Community Health Service Center in Yuexiu District,Guangzhou City,Fengyuan Street Community Health Service Center in Leiwan District,Guangzhou City,was evaluated as"excellent",and the allocation of TCM resources in 4 communities was rated as"poor".In addition,27,53 and 27 community health service centers were rated as"upper middle","medium"and"lower middle"respectively.Analysis of variance showed that the difference was statistically significant(F = 231.268,P<0.001).Conclusion TOPSIS method combined with RSR method can better evaluate the allocation of TCM resources in grass-roots communities:The allocation of TCM resources in grass-roots communities in Guangzhou is generally good,but there are still significant differences among different communities.In the future,health administrative departments at all levels in Guangzhou can rationally allocate resources according to the differences of different com-munities and better improve the capacity building of traditional Chinese medicine service in grassroots communities.