BACKGROUND:Mesenchymal stem cells are susceptible to senescence during in vitro expansion,which greatly hinders their application in vivo and in vitro.How to improve the replicative senescence of mesenchymal stem cells is an urgent problem to be solved in tissue engineering. OBJECTIVE:To determine whether vascular endothelial growth factor combined with basic fibroblast growth factor can improve the aging of bone marrow mesenchymal stem cells caused by replicative passage. METHODS:Rat bone marrow mesenchymal stem cells were extracted by whole bone marrow adhesion method.Passage 2 cells were selected as normal control group.Passage 7 and later algebraic cells were selected as aging model group.Vascular endothelial growth factor(50 μg/L),basic fibroblast growth factor(10 μg/L),and their combination were administered.Cell proliferation was detected by CCK-8 assay.Cell senescence was observed by β-galactosidase activity staining.Cytoskeleton size and colony formation ability were observed by phalloidine staining and Giemsa staining,respectively,and the levels of senescence-related genes P16,P21,and P53 were detected by qRT-PCR.Gene expression levels of P16,P21,and P53 were tested by qRT-PCR. RESULTS AND CONCLUSION:(1)Vascular endothelial growth factor combined with basic fibroblast growth factor could promote the proliferation of aged bone marrow mesenchymal stem cells,which began to enter the plateau stage on day 9,and the absorbance value of the combined intervention group was significantly higher than that of the model group on day 9(P<0.05).(2)The phenotypic markers of the cells in the combined intervention group did not change,and the cell morphology changed from broad to slender.(3)Compared with the model group,the positive rate of β-galactosidase was significantly decreased(P<0.01);the number of nuclei increased(P<0.001);the total area of cytoskeleton increased(P<0.01);colony formation ability was enhanced(P<0.05);expression level of P16 was decreased(P<0.01)in the combined intervention group.These results indicate that vascular endothelial growth factor combined with basic fibroblast growth factor can improve the senescence of bone marrow mesenchymal stem cells caused by replicative passage without changing the cell phenotype.

Objective To explore the effect of Kangxian Yixin decoction on PKA/CaMKⅡ Signal Pathway and Mitochondrial membrane potential of cardiomyocyte hypertrophy in dilated cardiomyopathy rats.Methods Drinking furazolidone to duplicate the DCM rats model for 10 weeks,then the rats were checked by ultrasound,the successfully established model rats were randomly divided into model group,low dose Kangxian Yixin decoction group,middle dose Kangxian Yixin decoction group,high dose Kangxian Yixin decoction group and captopril group.Normal group was separated.After 4 weeks of drug intervention,This experiment was over,ATP,Ca2+-Mg2+-ATP enzymatic activity,CaMKⅡ,PKA and UCP2 mRNA were tested.H9c2 cardiomyocyte hypertrophy model was set up by norepinephrine,after 24 h of drug intervention,mitochondrial membrane potential was tested.Results Compared with the normal group,cardiomyocyte mitochondria were damaged in each model group,ATP,Ca2+-Mg2+-ATP enzymatic activity and PKA mRNA were lower,UCP2 mRNA and CaMKⅡ mRNA were higer,mitochondrial membrane potential obviously decreased(P<0.05 or P<0.01).The mitochondria were protected in every drug group,the tested indexes get well in different degree,especially in hige dose Kangxian Yixin decoction group(P<0.05 or P<0.01).Conclusion Kangxian Yixin decoction can reduce myocardial cell mitochondrial damage in model rats with DCM,improve myocardial cell energy metabolism and cardiac systolic and diastolic functions,one of the mechanisms may be optimizing PKA/CaMKⅡ signal pathway and improving mitochondrial membrane potential.

Dilated cardiomyopathy(DCM)has a concealed onset with left or even whole heart enlargement as the main imaging manifestation.It is a common primary disease of heart failure and arrhythmia.With the continuous deepening of research in recent years,the intrinsic molecular mechanism of regulatory cell death(RCD)has gradually become clear.Researchers have found that the RCD mode plays a very important role in the occurrence and development of DCM.At present,the RCD modes involved in DCM mainly include apoptosis,necrotic apoptosis,pyroptosis,iron death,autophagy,and cuproptosis,and a certain correlation exists among them,which interact and regulate each other.This article provides an overview of the current research status on the mechanisms of the six RCD modes involved in DCM to provide a reference for future basic research and clinical applications.

Objective:To evaluate the efficacy of ultrasound-guided semispinalis capitis plane (SCP) block for treatment of occipital neuralgia (ON).Methods:This was a prospective study. Ninety patients of both sexes, aged 29-66 yr, suffering ON for 3 months-6 yr in Zibo Municipal Hospital from January 2022 to December 2023, were divided into 3 groups ( n=30 each) using a random number table method: combination of greater occipital nerve (GON) block and the third occipital nerve (TON) block group (group GT), SCP block via the medial head of semispinalis capitis muscle (SCM) group (group Sm), and SCP block via the space between obliquus capitis inferior and C 2, 3 facet joint (OCI-C 2, 3) group (group OC). In GT group, the analgesic and anti-inflammatory compound solution 2.5 ml was injected around GON in the SCM-OCI space at the C 2 level of the cervical vertebra and at the lateral surface of C 2, 3 facet joint. In Sm group, the analgesic and anti-inflammatory compound solution 5 ml was injected into the medial head of SCM at the level of C 1. In OC group, the analgesic and anti-inflammatory compound solution 5 ml was injected into the OCI-C 2, 3 space in the deep part of SCM. The Visual Analogue Scale (VAS) score and Pittsburgh Sleep Quality Index (PSQI) score were recorded before treatment (T 1) and at 1, 3, 7, 10 and 14 days after treatment (T 2-6), and then the rates of pain relief and improvement in sleep quality were calculated. The time spent in blocking, onset time of blocking, completion time of blocking, duration of block, and occurrence of adverse reactions within 24 h after block were recorded. Results:There were no significant differences in VAS scores and PSQI scores at T 1-3 and T 5-6 among the three groups ( P>0.05), and VAS and PSQI scores were significantly higher at T 4 in Sm group than in OC and GT groups ( P<0.05). Compared with GT group, the time spent in blocking was significantly shortened, the onset time and completion time of block was prolonged, and the duration of block was shortened in Sm group, and the time spent in blocking was significantly shortened, the onset time and completion time of block was shortened ( P<0.05), and no significant change was found in the duration of block in OC group ( P>0.05). No severe complications were observed in the three groups. Conclusions:Compared with the combination of GON and TON blocks, ultrasound-guided SCP block for treating ON is simple and highly safe, SCP block via the OCI-C 2, 3 space has rapid onset and long duration, leading to significant improvements in pain and sleep quality, and it can be used as the first-choice block method for treating ON.

Objective:To observe the anatomical characteristics of the semispinalis capitis plane (SCP) to provide a reference for clinically effective implementation of ultrasound-guided SCP block.Methods:Ultrasound scanning was performed in six certain districts of SCP in 30 healthy volunteers (60 sides). The key point was to examine and describe the anatomical characteristics of semispinalis capitis (SCA), deep space of SCA and structures within the space.Results:(1) Transverse scanning at the posterior arch of atlas revealed that the SCA was separated into medial and lateral head by an oblique thick septum; in the space between SCA and obliquus capitis inferior (SCA-OCI), the third occipital nerve (TON) and the greater occipital nerve (GON) were separated by a fascia.There was often a branch of occipital vein between them.The distance from TON to GON was (12.9±0.6) mm.(2) Transverse scanning at the lamina of axis revealed that the axial image of SCA and the structures in SCA-OCI space were similar to the results previously described in (1). The distance from TON to GON was (12.1±0.5) mm.(3) Sagittal scanning beside the spinous process of axis revealed that SCA was separated into superior and inferior belly by a septum which connected to the end of axis spinous process.(4) Sagittal scanning at the C 2, 3 facet joint revealed that in the space between OCI and C 2, 3 facet joint (OCI-C 2, 3) beneath SCA, there was no septum between TON and GON.The distance from TON to GON was (8.0±0.5) mm.(5) Transverse scanning at the lamina of C 4 revealed that in the space between SCA and semispinalis cervicis, the deep cervical artery and vein were observable except medial branch of C 4, and the characteristics of the short axis of the SCA belly were similar to the results previously described in (1). (6) Transverse scanning at the lamina of C 5 revealed that the view was similar to the results previously described in (5). The posterior branch of C 5 nerve was not found. Conclusions:SCP is rich in fascia, and blood vessels often pass through the deep surface space of SCA under ultrasound.The anatomical structure is complex, and there is individual variation.Grasping its ultrasonic anatomical characteristics is helpful in safely and effectively implementing ultrasound-guided SCP block.

Background: Postherpetic neuralgia (PHN) is the most common complication of acute herpes zoster. The treatment of PHN remains a challenge for clinical pain management. Despite the effectiveness of anticonvulsants, antidepressants, and lidocaine patches in reducing PHN, many patients still face intractable pain disorders.In this randomized controlled study, we evaluated whether hydromorphone through intravenous patient-controlled analgesia (IV PCA) was effective in relieving PHN. Methods: Patients with PHN were randomly divided into two groups, one group received oral pregabalin with IV normal saline, another group received oral pregabalin with additional IV PCA hydromorphone for two weeks. Efficacy was evaluated at 1, 4, and 12 weeks after the end of the treatments. Results: Two hundred and one patients were followed up for 12 weeks. After treatment, numerical rating scale (NRS) score of patients in the hydromorphone group was significantly lower than that of the control group, and the difference of NRS scores between the two groups was statistically significant at 4 and 12 weeks after treatment. The frequency of breakthrough pain in the hydromorphone group was significantly lower than that in the control group 1 and 4 weeks after treatment.After treatment, the quality of sleep in the hydromorphone group was significantly improved compared with the control group. The most common adverse reactions in the hydromorphone group were dizziness and nausea, with no significant respiratory depression. Conclusions IV PCA hydromorphone combined with oral pregabalin provides superior pain relief in patients with PHN, which is worthy of clinical application and promotion.

Background: Postherpetic neuralgia (PHN) is the most common complication of acute herpes zoster. The treatment of PHN remains a challenge for clinical pain management. Despite the effectiveness of anticonvulsants, antidepressants, and lidocaine patches in reducing PHN, many patients still face intractable pain disorders.In this randomized controlled study, we evaluated whether hydromorphone through intravenous patient-controlled analgesia (IV PCA) was effective in relieving PHN. Methods: Patients with PHN were randomly divided into two groups, one group received oral pregabalin with IV normal saline, another group received oral pregabalin with additional IV PCA hydromorphone for two weeks. Efficacy was evaluated at 1, 4, and 12 weeks after the end of the treatments. Results: Two hundred and one patients were followed up for 12 weeks. After treatment, numerical rating scale (NRS) score of patients in the hydromorphone group was significantly lower than that of the control group, and the difference of NRS scores between the two groups was statistically significant at 4 and 12 weeks after treatment. The frequency of breakthrough pain in the hydromorphone group was significantly lower than that in the control group 1 and 4 weeks after treatment.After treatment, the quality of sleep in the hydromorphone group was significantly improved compared with the control group. The most common adverse reactions in the hydromorphone group were dizziness and nausea, with no significant respiratory depression. Conclusions IV PCA hydromorphone combined with oral pregabalin provides superior pain relief in patients with PHN, which is worthy of clinical application and promotion.

Objective To investigate the potential therapeutic effect of luteolin on sepsis-induced ALI and the underlying mechanisms.Methods Total of 50 mice were randomly(random number) divided into five groups:a sham control group,a sepsis-induced ALI group,and three sepsis groups pre-treated with 20,40,and 80 mg/kg body weight luteolin.Mice in the treatment groups were pre-treated with luteolin at the respective oral dose two days before ALI induction.The lungs were isolated for histopathological examinations,and the bronchoalveolar lavage fluid (BALF) was collected for biochemical analyses.Results Luteolin significantly attenuated sepsis-induced ALI.Additionally,luteolin treatment decreased protein and inflammatory cytokine concentration and the number of infiltrated inflammatory cells in BALF compared with that in the non-treated sepsis mice.Pulmonary myeloperoxidase (MPO) activity was lower in the luteolin-pre-treated sepsis groups than in the sepsis group.The mechanism underlying the protective effect of luteolin on sepsis is related to the up-regulation of certain antioxidation genes,including inducible nitric oxide synthase (iNOS),cyclooxygenase-2 (COX-2),superoxide dismutases (SODs),and heme oxygenase 1 (HO-1),and the reduction of inflammatory responses through blockage of the activation of the nuclear factor (NF)-κB pathway.Conclusions Luteolin pre-treatment inhibits sepsis-induced ALI through its anti-inflammatory and antioxidative activity,suggesting that luteolin may be a potential therapeutic agent for sepsis-induced ALI.

Objective: To explore the relationship between job stress, work engagement and depressive symptoms of State Grid workers, and to analyze the mediating effect of work engagement between job stress and depressive symptoms. Methods: A cross-sectional survey was conducted to investigate 845 employees from a State Grid company, using the brief job stress questionnaire, the Patient Health Questionnaire (PHQ-9) and 9-item Utrecht Work Engagement Scale (UWES-9) in March 2017. Results: The average score of work engagement was 4.49±1.42, the mean value of job stress was 1.15±0.33, the average score of depressive symptoms was 6.44±4.30, and the positive rate of depressive symptoms was 66.9%.There was a negative correlation between work engagement with both job stress and depressive symptoms (r=-0.193, -0.397, both P<0.01) , and job stress was positively correlated with depressive symptoms (r=0.260, P<0.01) . The relationship between job stress and depressive symptoms was partly mediated by work engagement, and the mediating effect accounted for 27.2% of the total effect. Conclusion The work engagement of State Grid staff acts as the mediator between job stress and depressive symptoms, alleviating the depressive symptoms caused by job stress.

Objective To study the effect of artesunate on inflammatory responses to severe pneumonia by regulating macrophage migration inhibitory factor (MIF) in rats.Methods Total of 100 SD by random (random number) assigned,20 rats were control group,80 SD rats with severe pneumonia were caused by Klebsiella pneumoniae,60 SD rats were treated with different concentrations (20,40,80 mk/kg) of artesunate after modeling.The pathological changes of lung tissue,the level of MIF myeloperoxidase activity and inflammatory cell infiltration in lung tissue of rats were evaluated.Results After treatment with artesunate,the severity of inflammation was significantly alleviated in rats with severe pneumonia evidenced by decrease in myeloperoxidase activity [severe pneumonia:(17.5 ± 1.5) vs.treatment group:(7.5 ±2.0)] and reduction in inflammatory cell infiltration (severe pneumonia:27 × 106 vs.treatment group:12.5 × 106).Similarly,the artesunate also reduced the production of inflammatory cytokines significantly in bronchoalveolar lavage fluid (IL-1 in severe pneumonia group:(1 100 ± 50) pg/ml vs.treatment group:(400 ± 60) pg/ml;IL-6 in severe pneumonia group:(700-± 30) pg/ml vs.treatment group:(200 ±40) pg/ml;IL-10 in severe pneumonia group:(500 ± 70) pg/ml vs.treatment group:(200 ± 40) pg/ml;TNF-αin severe pneumonia group:(500 ± 80) pg/ml vs.treatment group:(150 ± 50) pg/ml.In addition,artesunate inhibited the level and production of MIF,thus inhibiting the inflammatory responses mediated by MIF.Conclusions Artesunate had a protective effect on pneumonia caused by Klebsiella pneumoniae in rats via inhibiting the inflammation responses mediated by MIF.This study provided a molecular basis for newly developed drugs applied to the treatment of pneumonia caused by Klebsiella pneumoniae in rats.