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 investigate the toxicokinetic differences of 3,4-methylenedioxy-N-methylamphetamine(MDMA)and its metabolite 4,5-methylene dioxy amphetamine(MDA)in rats af-ter single and continuous administration of MDMA,providing reference data for the forensic identifica-tion of MDMA.Methods A total of 24 rats in the single administration group were randomly divided into 5,10 and 20 mg/kg experimental groups and the control group,with 6 rats in each group.The ex-perimental group was given intraperitoneal injection of MDMA,and the control group was given intraperi-toneal injection of the same volume of normal saline as the experimental group.The amount of 0.5 mL blood was collected from the medial canthus 5 min,30 min,1 h,1.5 h,2 h,4 h,6 h,8 h,10 h,12 h after administration.In the continuous administration group,24 rats were randomly divided into the experi-mental group(18 rats)and the control group(6 rats).The experimental group was given MDMA 7 d by continuous intraperitoneal injection in increments of 5,7,9,11,13,15,17 mg/kg per day,respectively,while the control group was given the same volume of normal saline as the experimental group by in-traperitoneal injection.On the eighth day,the experimental rats were randomly divided into 5,10 and 20 mg/kg dose groups,with 6 rats in each group.MDMA was injected intraperitoneally,and the con-trol group was injected intraperitoneally with the same volume of normal saline as the experimental group.On the eighth day,0.5 mL of blood was taken from the medial canthus 5 min,30 min,1 h,1.5 h,2 h,4 h,6 h,8 h,10 h,12 h after administration.Liquid chromatography-triple quadrupole tandem mass spectrometry was used to detect MDMA and MDA levels,and statistical software was employed for data analysis.Results In the single-administration group,peak concentrations of MDMA and MDA were reached at 5 min and 1 h after administration,respectively,with the largest detection time limit of 12 h.In the continuous administration group,peak concentrations were reached at 30 min and 1.5 h af-ter administration,respectively,with the largest detection time limit of 10 h.Nonlinear fitting equations for the concentration ratio of MDMA and MDA in plasma and administration time in the single-administration group and continuous administration group were as follows:T=10.362C-1.183,R2=0.974 6;T=7.397 3C-0.694,R2=0.961 5(T:injection time;C:concentration ratio of MDMA to MDA in plasma).Conclusions The toxicokinetic data of MDMA and its metabolite MDA in rats,obtained through single and continuous administration,including peak concentration,peak time,detection time limit,and the relationship between concentration ratio and administration time,provide a theoretical and data foundation for relevant forensic identification.

Social behavior is extremely important for the physical and mental health of individuals, their growth and development, and for social development. Social behavioral disorders have become a typical clinical representation of a variety of psychiatric disorders and have serious adverse effects on the development of individuals. The prefrontal cortex, as one of the key areas responsible for social behavior, involves in many advanced brain functions such as social behavior, emotion, and decision-making. The neural activity of prefrontal cortex has a major impact on the performance of social behavior. Numerous studies demonstrate that neurons and glial cells can regulate certain social behaviors by themselves or the interaction which we called neural microcircuits; and the collaboration with other brain regions also regulates different types of social behaviors. The prefrontal cortex (PFC)-thalamus projections mainly influence social dominance and social preference; the PFC-amygdala projections play a key role in fear behavior, emotional behavior, social exploration, and social identification; and the PFC-nucleus accumbens projections mainly involve social preference, social memory, social cognition, and spatial-social associative learning. Based on the above neural mechanism, many studies have focused on applying the non-invasive neurostimulation to social deficit-related symptoms, including transcranial magnetic stimulation (TMS), transcranial electrical stimulation (TES) and focused ultrasound stimulation (FUS). Our previous study also investigated that repetitive transcranial magnetic stimulation can improve the social behavior of mice and low-intensity focused ultrasound ameliorated the social avoidance behavior of mice by enhancing neuronal activity in the prefrontal cortex. In this review, we summarize the relationship between neurons, glial cells, brain projection and social behavior in the prefrontal cortex, and systematically show the role of the prefrontal cortex in the regulation of social behavior. We hope our summarization will provide a reference for the neural mechanism and effective treatment of social disorders.

ObjectiveDetection and quantification of RNA synthesis in cells is a widely used technique for monitoring cell viability, health, and metabolic rate.After exposure to environmental stimuli, both the internal reference gene and target gene would be degraded. As a result, it is imperative to consider the accurate capture of nascent RNA and the detection of transcriptional levels of RNA following environmental stimulation. This study aims to create a Click Chemistry method that utilizes its property to capture nascent RNA from total RNA that was stimulated by the environment. MethodsThe new RNA was labeled with 5-ethyluridine (5-EU) instead of uracil, and the azido-biotin medium ligand was connected to the magnetic sphere using a combination of “Click Chemistry” and magnetic bead screening. Then the new RNA was captured and the transcription rate of 16S rRNA was detected by fluorescence molecular beacon (M.B.) and quantitative reverse transcription PCR (qRT-PCR). ResultsThe bacterial nascent RNA captured by “Click Chemistry” screening can be used as a reverse transcription template to form cDNA. Combined with the fluorescent molecular beacon M.B.1, the synthesis rate of rRNA at 37℃ is 1.2 times higher than that at 15℃. The 16S rRNA gene and cspI gene can be detected by fluorescent quantitative PCR,it was found that the measured relative gene expression changes were significantly enhanced at 25℃ and 16℃ when analyzed with nascent RNA rather than total RNA, enabling accurate detection of RNA transcription rates. ConclusionCompared to other article reported experimental methods that utilize screening magnetic columns, the technical scheme employed in this study is more suitable for bacteria, and the operation steps are simple and easy to implement, making it an effective RNA capture method for researchers.

Cordycepin (Cpn), a natural active compound derived from the traditional Chinese medicine Cordyceps sinensis, has antifibrotic, antioxidant, and anti-inflammatory effects, but the impact of Cpn on pulmonary fibrosis and the downstream molecular mechanism remain unclear. In this study, A549 cells were induced by transforming growth factor β1 (TGFβ1) in vitro, the viability of A549 cells was evaluated by CCK-8 assay; and migration of A549 cells were detected by wound healing assay, invasion of A549 cells were detected by transwell assay. Molecular docking and molecular dynamics simulations were used to predict the interaction of histone deacetylase 7 (HDAC7) with vimentin and the association of Cpn with HDAC7. The pulmonary fibrosis model of mice was established by bleomycin in vivo to investigate the effect of Cpn on pathological changes of lung tissue. The impact of Cpn and molecular mechanism on pulmonary fibrosis were studied by Western blot assay, cell transfection assay, immunoprecipitation assay, immunofluorescence assay, immunohistochemistry and real-time quantitative PCR (RT-qPCR). All animal experiments were approved by the Shanghai Children's Medical Center Experimental Animal Ethics Committee (grant No. SCMC-LAWEC-2022-017). Results showed that Cpn had no toxic effect on A549 cells even at the concentration of 100 μmol·L^-1. Cpn inhibited migration and invasion of A549 cells and reduced deposition of collagen, the degree of lung inflammation and fibrosis in mice; in vivo and in vitro models, Cpn significantly reversed mRNA and protein expressions of epithelial-mesenchymal transition (EMT) and lung fibrosis markers collagen I, α-smooth muscle actin (α-SMA), N-cadherin, vimentin and E-cadherin and HDAC7. Deficiency of HDAC7 suppressed TGFβ1-induced EMT and expression of collagen I; vimentin interacted with HDAC7; and molecular docking experiment revealed that Cpn was interrelated with HDAC7. In conclusion, Cpn can target HDAC7 to mediate EMT and exert its anti-fibrotic effect, the inhibition of EMT and the improvement of pulmonary fibrosis provide a new idea and choice for the development of anti-pulmonary fibrosis drug.

Objective To analyze the therapeutic effects and survival benefits of sintilimab combined with albumin-bound paclitaxel chemotherapy in the treatment of patients with advanced gastric cancer.Methods Patients with advanced gastric cancer were divided into the treatment group and the control group by cohort method.The control group was treated with albumin-bound paclitaxel-based chemotherapy[intravenous infusion of albumin-bound paclitaxel at 125 mg·m-2 from day 1 to day 8,for a cycle(21 days as a cycle);Tiggio capsule 40 mg·m-2·d-1 was taken orally for 1-14 days for 1 consecutive cycle;Trastuzumab was administered once every 3 weeks at an initial loading dose of 8 mg·kg-1,followed by maintenance treatment at a dose of 6 mg·kg-1 every 3 weeks].On this basis,the treatment group was treated with intravenous infusion of sintilimab injection at a dose of 200 mg·time-1 on the first day of each cycle,with 21 d as a cycle.After 6 cycles of continuous treatment,both groups were given maintenance treatment and were followed up for 8 months.The two groups were compared in terms of clinical efficacy,the levels of serum tumor markers[carbohydrate antigen 242(CA242),carbohydrate antigen 724(CA724),carcinoembryonic antigen(CEA),tissue polypeptide-specific antigen(TPS),soluble intercellular cell adhesion molecule-1(sICAM-1)and E-cadherin],survival and evaluated the safety.Results In this study,39 and 41 patients were enrolled in the control group and the treatment group,respectively.At the end of treatment,the objective response rates(ORR)in the treatment group and the control group were 56.10％and 33.33％;the disease control rates(DCR)were 78.05％and 48.71％.The differences were statistically significant(all P＜0.05).After treatment,serum CA242 levels in the treatment group and the control group were(57.64±5.82)and(68.95±7.23)mg·L-1;CA724 levels were(36.58±3.79)and(43.65±4.48)U·mL-1;CEA levels were(17.33±1.78)and(20.16±2.35)ng·mL-1;TPS levels were(21.35±2.44)and(37.65±3.84)U·L-1;sICAM-1 levels were(216.77±22.53)and(275.34±28.63)ng·mL-1;E-cadherin levels were(12.15±1.36)and(9.87±1.45)ng·mL-1.The differences were statistically significant(all P＜0.05).The average progression free survival(PFS)of the treatment group and the control group was 7.55 months and 7.17 months;PFS rates were 65.78％and 56.42％.The differences were statistically significant(P＜0.05).The adverse drug reactions in the treatment group and the control group were mainly bone marrow suppression,nausea and vomiting,liver function damage,peripheral nerve paresthesia,and hypothyroidism.There was no statistically significant difference in the above adverse drug reactions between the treatment group and the control group(all P＞0.05).Conclusion Sintilimab combined with albumin-bound paclitaxel chemotherapy is effective in the treatment of patients with advanced gastric cancer,which can significantly improve serum tumor markers and prolong PFS,with good safety.

Objective:To investigate the diagnostic value of serum ferritin in intestinal failure-associated liver disease. Methods:Clinical data of adult patients with short bowel syndrome admitted to the Department of General Surgery of Jinling Hospital affiliated to Nanjing University from January 2019 to December 2022 were retrospectively analyzed to determine the correlation between serum ferritin and liver enzyme profiles by linear regression,to screen the potential risk factors of liver injury by multifactorial Logistic regression analysis,and to establish a prediction model for liver fibrosis. The area under the curve was also calculated to assess the accuracy of the model. Results:A total of 106 patients with short bowel syndrome were included,of whom 55 (51.9％) had elevated serum ferritin (SF). Linear regression analysis showed a positive correlation between serum ferritin and ALT (r=0.427,P<0.001),ALP (r=0.365,P<0.001),and γ-GT (r=0.423,P<0.001),and one-way Logistic regression analysis showed that the higher the level of serum ferritin,the more pronounced the difference was (SF>ULN) The one-way logistic regression analysis showed that the higher the serum ferritin level,the more significant the difference was[SF>ULN (upper limit of normal value of serum ferritin),P=0.033;SF>1.5×ULN,P=0.018;SF>2.5×ULN,P=0.006]. Multifactorial logistic regression analysis showed that PN dependence (OR=3.366,P=0.017) and serum ferritin>2.5 ULN (OR=3.292,P=0.014)were independent risk factors for intestinal failure-associated liver disease-liver fibrosis,and the receiver operating curve (ROC) of the subjects showed area under the curve of 74.8％,95％ CI:0.652～0.844. Conclusion:Serum ferritin can be used as a reliable clinical biomarker to help identify intestinal failure-associated liver disease.

Objective To investigate the protective effect of placental mesenchymal stem cells(P-MSCs)on pancreatic trauma(PT)in rats.Methods Sixty healthy adult male SD rats were randomly divided into control group,pancreatic trauma group(inject 1 ml of PBS solution locally in the pancreatic injury area and around the trauma area),and P-MSCs group[inject 1 ml of P-MSCs(1×106/ml)locally in the pancreatic injury area and around the trauma area],with 20 rats in each group.The pancreatic trauma rat model was established using a traumatic pressure of 400 kPa.Five rats were sacrificed at 1,3,5,and 7 d after modeling in each group,and serum and pancreatic tissue were collected.HE staining was used to observe the pathological changes of pancreatic tissue and pathological scores were performed.The ELISA method was used to measure the concentrations of serum amylase(AMS),lipase(LPS),tumor necrosis factor-α(TNF-α),interleukin-6(IL-6),IL-10,and transforming growth factor-β1(TGF-β1),as well as the activities of myeloperoxidase(MPO)and superoxide dismutase(SOD)in pancreatic tissue.The TUNEL method was used to observe the level of apoptosis in pancreatic tissue was observed by the TUNEL method.Results Compared with control group,pancreatic trauma group and P-MSCs group showed significant differences after pancreatic trauma,including the generation of peritoneal fluid increased(P<0.05),the ratio of pancreas to body weight and the total score of pancreatic tissue pathological damage increased(P<0.05),and serum levels of AMS,LPS,TNF-α,IL-6,and MPO activity increased early and showed a decreasing trend over time(P<0.05),while anti-inflammatory factors IL-10 and SOD activity showed an increasing trend over time(P<0.01),level of TGF-β1 in the early decline showed an upward trend over time(P<0.01),and the apoptosis index(AI)significantly increased(P<0.001).Compared with pancreatic trauma group,P-MSCs group showed an improvement in the overall morphology of pancreatic tissue,the generation of peritoneal fluid decreased(P<0.001),the pancreas to body weight ratio and the total score of pancreatic tissue pathological damage decreased(P<0.05),and serum levels of AMS,LPS,IL-6,TNF-α and MPO activity returned to normal levels faster(P<0.05);and the rate of anti-inflammatory factors IL-10,TGF-β1 and SOD activity elevation increased(P<0.05),the AI increased(P<0.001).Conclusion P-MSCs can achieve therapeutic effects on pancreatic trauma in rats by promoting pancreatic tissue repair,reducing local and systemic inflammation,improving tissue oxidative stress,and enhancing pancreatic acinar cell apoptosis.

Objective To compare the efficacies of retrograde tibial nailing(RTN)versus minimally invasive percutaneous plate osteosynthesis(MIPPO)in the treatment of distal tibial fractures.Methods A retrospective analysis was conducted on the clinical data of 55 patients with distal tibial fractures who underwent surgery in our hospital.Patients were divided into two groups based on the different surgical methods,patients in the RTN group(n=25)were treated with RTN,and patients in the MIPPO group(n=30)were treated with MIPPO.The surgical parameters(operation time,intraoperative blood loss,intraoperative fluoroscopy times,and success rate of closed reduction),fracture healing time,ankle dorsiflexion range of motion and American Orthopaedic Foot and Ankle Society(AOFAS)ankle-hindfoot scores 6 months after operation and at the last follow-up,and the incidence of complications during perioperative period and follow-up were compared between the two groups.Results The operation time,intraoperative blood loss,and intraoperative fluoroscopy times in the RTN group were significantly shorter/less than those in the MIPPO group(P＜0.05).The ankle dorsiflexion range of motion and AOFAS ankle-hindfoot score 6 months after operation in the RTN group were significantly greater/higher than those in the MIPPO group(P＜0.05).There was no statistically significant difference in the fracture healing time,or ankle dorsiflexion range of motion and AOFAS ankle-hindfoot score at the last follow-up between the two groups(P＞0.05).The success rate of closed reduction in the RTN group was 72.00％,which was lower than that of 96.67％in the MIPPO group(P＜0.05).The incidence of soft tissue-related complications in the RTN group was signifi-cantly lower than that in the MIPPO group(P＜0.05),while there was no statistically significant difference in the overall incidence of complica-tions between the two groups(P＞0.05).Conclusion RTN is an effective minimally invasive surgical technique for the treatment of distal tibial fractures,characterized by minimal trauma,low incidence of soft tissue complications,and fast recovery of joint function compared with MIPPO.

Objective:To explore the genotypes and frequency distribution of thalassemia in Lingui District,Guilin City,and provide reference for the prevention and control of thalassemia in this area. Methods:The results of genetic testing for thalassemia in 1501 suspected cases at the Second Affiliated Hospital of Guilin Medical University were analyzed retrospectively. The deletional mutations of α-thalassemia were detected by gap-PCR,the non-deletional mutations of α-thalassemia and β-thalassemia mutations were detected by PCR-reverse dot blot (PCR-RDB). Results:In 1501 samples,a total of 678 cases of thalassemia carriers were detected,with a detection rate of 45.17％. Among them,379 cases were α-thalassemia (including deletional α-thalassemia and non-deletional α-thalassemia),with a detection rate of 25.25％,the most common genotype was--SEA/αα (227 cases,15.12％),followed by-α3.7/αα (53 cases,3.53％). 270 cases of β-thalassemia were detected,with a detction rate of 17.99％,and βCD41-42/βN (144 cases,9.59％) was the main genotypes,followed by βCD17/βN (66 cases,4.40％) . In addition,there were 29 cases of αβ compound thalassemia,accounting for 1.93％,and the most common genotype was--SEA/αα complex βCD41-42/βN (5 cases,0.33％). Conclusion:Lingui District in Guilin City is a high-incidence area of thalassemia,and the genotypes of carriers are complex and diverse,with genetic heterogeneity. The results of this study provide a scientific basis for genetic counseling and prenatal diagnosis in this area.