Patients suffering from nerve injury often experience exacerbated pain responses and complain of memory deficits. The dorsal hippocampus (dHPC), a well-defined region responsible for learning and memory, displays maladaptive plasticity upon injury, which is assumed to underlie pain hypersensitivity and cognitive deficits. However, much attention has thus far been paid to intracellular mechanisms of plasticity rather than extracellular alterations that might trigger and facilitate intracellular changes. Emerging evidence has shown that nerve injury alters the microarchitecture of the extracellular matrix (ECM) and decreases ECM rigidity in the dHPC. Despite this, it remains elusive which element of the ECM in the dHPC is affected and how it contributes to neuropathic pain and comorbid cognitive deficits. Laminin, a key element of the ECM, consists of α-, β-, and γ-chains and has been implicated in several pathophysiological processes. Here, we showed that peripheral nerve injury downregulates laminin β1 (LAMB1) in the dHPC. Silencing of hippocampal LAMB1 exacerbates pain sensitivity and induces cognitive dysfunction. Further mechanistic analysis revealed that loss of hippocampal LAMB1 causes dysregulated Src/NR2A signaling cascades via interaction with integrin β1, leading to decreased Ca²⁺ levels in pyramidal neurons, which in turn orchestrates structural and functional plasticity and eventually results in exaggerated pain responses and cognitive deficits. In this study, we shed new light on the functional capability of hippocampal ECM LAMB1 in the modulation of neuropathic pain and comorbid cognitive deficits, and reveal a mechanism that conveys extracellular alterations to intracellular plasticity. Moreover, we identified hippocampal LAMB1/integrin β1 signaling as a potential therapeutic target for the treatment of neuropathic pain and related memory loss.
Animals ; Laminin/genetics* ; Hippocampus/metabolism* ; Neuralgia/metabolism* ; Cognitive Dysfunction/etiology* ; Male ; Peripheral Nerve Injuries/metabolism* ; Extracellular Matrix/metabolism* ; Integrin beta1/metabolism* ; Pyramidal Cells/metabolism* ; Signal Transduction

Fuxiong has a long history of cultivation. Since its first record in the Beneficial Formulas from the Taiping Imperial Pharmacy of the Song Dynasty, Fuxiong had always been used by ancient physicians and became a preponderant variety for some reasons during the periods of the Ming Dynasty, Qing Dynasty, and Republic of China. However, as for modern use, only Chuanxiong Rhizoma is valued, and the medicinal value of Fuxiong is gradually being overlooked. This article systematically researches the nomenclature, producing area, origin, and efficacy of Fuxiong, proving that the planting technology of Fuxiong matured in the Song Dynasty at the latest, slightly later than the emergence of Chuanxiong Rhizoma in the Sui and Tang Dynasties. Over the years, the producing area of Fuxiong has not undergone significant changes, and it is mainly cultivated within Jiangxi province. According to the analysis of the origin of Xiongqiong, combined with modern genetic research, it can be basically clarified that the early source of Xiongqiong may not be single. With the popularization of cultivation, Chuanxiong Rhizoma became a Dao-di herb earliest, gradually replacing Xiongqiong and being recognized clinically. After cultivation, the polyploidy of Chuanxiong Rhizoma varieties formed stable inheritance, forming the later Fuxiong. Medical experts have gradually deepened their understanding of the efficacy of Fuxiong. Initially, they believed that it was a substitute for Chuanxiong Rhizoma and had weaker efficacy than Chuanxiong Rhizoma. Medical experts in Jin and Yuan Dynasties such as Zhu Danxi and Dai Sigong believed that Fuxiong was good at relieving stagnation. Books and records of materia medica in the Ming and Qing Dynasties explicitly proposed the great ability of Fuxiong to relieve stagnation. Fuxiong should be distinguished from Chuanxiong Rhizoma when applied, and the application differences should be clearly reflected in medical records. Based on the comprehensive research in this article, it can be concluded that although most of ancient physicians have attached great importance to genuineness of Chuanxiong Rhizoma, Fuxiong, as a dominant variety of traditional application, has a clear historical context and significant efficacy characteristics, worthy of further in-depth study.
Drugs, Chinese Herbal/history* ; China ; Medicine, Chinese Traditional/history* ; History, Ancient ; Humans ; History, Medieval ; Plants, Medicinal/chemistry* ; Rhizome/growth & development*

The purpose of the present study was to investigate the effects of resistance combined with aerobic chrono-exercise on the common carotid artery elasticity and hemodynamics. 24 healthy young men (21.96±0.43 years old) underwent a single acute resistance combined with aerobic exercise intervention at eight time periods (6, 8, 10, 12, 14, 16, 18, and 20 o'clock). The axial flow velocity and diameter waveforms of the common carotid artery were measured, and the hemodynamics were calculated using the classical hemodynamic theory before exercise, immediately after exercise, 10 min and 20 min after exercise. The results showed that during exercise recovery, systolic and mean pressures decreased more markedly after exercise at 8 o'clock (P < 0.05); At 20 min post-exercise, arterial stiffness index and pressure-strain elastic modulus after exercise at 6 o'clock were reduced compared with the resting state, but were significantly elevated after exercise at 20 o'clock (P < 0.05). Immediately after exercise, the pressure rise was higher after exercise at 6 o'clock and the mean wall shear stress was higher after exercise at 20 o'clock (P < 0.05). These results suggest that resistance combined with aerobic chrono-exercise produces different effects on common carotid artery hemodynamics in young men. A single acute session of resistance combined with aerobic exercise at 8 o'clock is more effective in lowering blood pressure. Exercise at 6 o'clock is beneficial to improve arterial elasticity but is not recommended for young male individuals with cardiovascular disease risks because of the excessive increase in blood pressure immediately after exercise. Exercise at 20 o'clock is more effective in improving wall shear stress but is accompanied by elevated arterial stiffness indices and pressure-strain elastic modulus. These results provide a scientific basis for healthy young men in choosing the time of exercise by exploring the common carotid artery elasticity and hemodynamic-related indices.
Humans ; Male ; Young Adult ; Exercise/physiology* ; Carotid Artery, Common/physiology* ; Hemodynamics/physiology* ; Vascular Stiffness/physiology* ; Elasticity ; Resistance Training ; Adult

A method for determination and targeted screening of diflorasone components in health products using ultra performance liquid chromatography-quadrupole time of flight mass spectrometry(UPLC-Q-TOF/MS)was established.Four representative diflorasone and esters(diflorasone,diflorasone diacetate,diflorasone-17-propionate,and diflorasone-21-propionate)were selected to optimize the pretreatment conditions,and 10 mL of extraction solvent dosage,15 min of extraction time and 5 g of salting-out agent as the optimal conditions were selected by response surface methodology.The results showed that the four analytes exhibited good linearity within the concentration range of 2.0?100 μg/L with the chromatographic peak area,and the correlation coefficients(R2)were all greater than 0.9990,while the results of recovery and relative standard deviation could satisfy the requirements of determination.The common characteristic ions of diflorasone and esters werem/z121 andm/z335,and their specific structures were obtained by analyzing the cleavage pathway based on the optimized determination conditions.A targeted screening method for other esters of diflorasone based on characteristic ions guidance strategy was established.This method had many advantages such as high efficiency,high sensitivity and good reproducibility,and could be used for targeted screening of diflorasone and esters in health products.The developed characteristic ion guided strategy could be employed to construct mass spectral databases for various glucocorticoids,enabling comprehensive targeted screening across a broad range of compounds.

Objective To compare the efficacy and safety of empagliflozin and linagliptin in the treatment of patients with type 2 diabetes mellitus(T2DM)with heart failure(HF).Methods Patients with T2DM and HF were randomly into control group and treatment group.Both groups were treated with individualized anti-HF and metformin-based hypoglycemic therapy.On this basis,the control group was given linagliptin orally(5 mg each time,once a day),while the treatment group was given oral administration of empagliflozin 10 mg every day.Patients in both groups were treated continuously for 6 months.The clinical efficacy and blood glucose indicators[fasting blood glucose(FBG),2 h postprandial blood glucose(2 h PBG),hemoglobin A1c(HbA1c)],cardiac molecular markers[N-terminal pro-brain natriuretic peptide(NT-proBNP),fibroblast growth factor 23(FGF23),copeptin(CPP)]and caridac function indicators[left ventricular end-diastolic diameter(LVEDD),left ventricular ejection fraction(LVEF),left ventricular remodeling index(LVRI)]before and after treatment were compared,and the adverse drug reactions were recorded.Results There were 40 cases in treatment group and 40 cases in control group.After treatment,the total effective rates in treatment group and control group were 97.50％(39 cases/40 cases)and 80.00％(32 cases/40 cases),with no significant difference(P＜0.05).The FBG levels in treatment group and control group were(7.64±1.18)and(7.83±1.24)mmol·L-1;2 h PBG levels were(8.97±1.46)and(9.04±1.35)mmol·L-1;HbA1c levels were(7.58±1.27)％and(7.65±1.42)％,all with no significant difference(all P＞0.05).The NT-proBNP levels in treatment group and control group were(612.53±204.62)and(1 045.24±316.75)pg·mL-1;FGF23 levels were(362.74±62.61)and(493.27±74.64)μg·L-1;CPP levels were(12.58±3.43)and(16.87±4.36)pmol·L-1;LVEDD values were(51.19±2.36)and(53.35±2.24)mm;LVEF values were(52.69±3.38)％and(50.28±3.75)％;LVRI values were(2.62±0.29)and(2.96±0.33)kg·L-1,all with significant difference(all P＜0.05).The incidence rates of adverse reactions in treatment group and control group were 5.00％(2 cases/40 cases)and 10.00％(4 cases/40 cases),with no significant difference(P＞0.05).Conclusion Both empagliflozin and linagliptin can effectively reduce the blood glucose in patients with T2DM complicated with HF.Empagliflozin can better promote the improvement of cardiac function in patients without significantly increase the incidence of adverse drug reactions.

Objective To explore the regulatory mechanism of Macelignan on oxidative stress-mediated neuronal injury in autophagy and apoptosis.Methods Murine hippocampal neuronal HT22 cells were treated with 2.5 mmol·L-1 glutamic acid(Glu)to establish an oxidative stress cell model.The cells were divided into normal group(normal cultured cells),model group(2.5 mmol·L-1 Glu)and experimental-L,-M,-H groups(2.5,5,10 μmol·L-1Macelignan treatment),inhibitor group(2.5 mmol·L-1 Glu+10 μmol·L-1 Macelignan+10 μmol·L-1 LY294002).Aoptosis rate was detected by flow cytometry;the protein expression level of autophagy-related protein LC3B(LC3B),anti-SQSTM1/p62(p62),p21,B-cell lymphoma-2(Bcl-2)and Bcl-2 associated X protein(Bax)was detected by Western blot.Results The apoptosis rates in the normal group,model group and experimental-L,-M,-H groups were(4.58±1.25)％,(8.75±0.55)％,(6.30±1.71)％,(5.97±2.27)％and(5.49±1.71)％.The difference between model group and normal group was statistically significant(P＜0.01).The difference between experimental-L,-M,-H groups and model group was statistically significant(all P＜0.01).The levels of LC3B in normal group,model group,experimental-L,experimental-M,experimental-H groups and inhibitor group were 0.28±0.02,0.74±0.02,1.02±0.04,0.70±0.03,0.26±0.02 and 0.21±0.01;p62 levels were 0.49±0.08,0.33±0.03,0.50±0.07,0.59±0.01,0.64±0.13 and 0.65±0.06;p21 levels were 0.87±0.02,1.18±0.03,0.98±0.03,0.88±0.03,0.72±0.06 and 0.81±0.02;Bcl-2/Bax levels were 1.74±0.23,1.11±0.10,1.38±0.05,1.66±0.26,1.58±0.29 and 1.53±0.09,respectively.The differences between model group and normal group,between model group and experimental-H group,between model group and inhibitor group,were also statistically significant(all P＜0.01).Conclusion Macelignan can reduce the damage of hippocampal neurons induced by glutamate acid by regulating the process of autophagy and apoptosis,and has obvious neuroprotective effect.

Objective To study the bioequivalence of test and reference olmesartan tablet in Chinese healthy subjects after single dose under fasting and fed conditions.Methods A single-center,random,open,single-dose,two-preparations,double-period,crossover study was adopted.A total of 48 healthy adult male and female subjects(24 cases of fasting test and 24 cases of fed test)were included in the random crossover administration.Single oral dose 20 mg of test and reference were taken under fasting and postprandial conditions,respectively.Plasma concentration of olmesartan in plasma were determined by liquid chromatography tandem mass spectrometry.The main pharmacokinetic parameters were calculated by Phoenix WinNonlin 8.0 software.Results The main pharmacokinetic parameters of the test and reference preparations of olmesartan tablets in the fasting group were as follows:Cmax were(653.06±133.53)and(617.37±151.16)ng·mL-1,AUC0-t were(4 201.18±1 035.21)and(4 087.38±889.99)ng·mL-1·h,AUC0-∞ were(4 254.30±1 058.90)and(4 135.69±905.29)ng·mL-1·h.The main pharmacokinetic parameters of the test and reference preparations of olmesartan tablets in the postprandial group were as follows:Cmax were(574.78±177.05)and(579.98±107.74)ng·mL-1,AUC0-t were(3 288.37±866.06)and(3 181.51±801.06)ng·mL-1·h,AUC0-∞ were(3 326.11±874.26)and(3 242.01±823.09)ng·mL-1·h.Under fasting and postprandial conditions,the 90％confidence intervals of the main pharmacokinetic parameters of the test and reference preparations are both 80.00％-125.00％.Conclusion Under fasting and postprandial conditions,a single oral dose of test and reference preparations olmesartan tablets in Chinese healthy adult volunteers showed bioequivalence.

Aim To investigate the effect of Celastrol on the expression of Ezrin in tissues and HaCaT cells of DNCB sensitisation-induced atopic dermatitis(AD)mice.Methods BALB/c mice were taken and ran-domly divided into the control,DNCB group,Celastrol 25 μg,50 μg,75 μg treatment group,and Dex group,with 8 mice in each group;HaCaT cells were induced with TNF-α and treated with 1 μmol·L-1 Celastrol and Ezrin siRNA.The thickness of the skin on the ear and back of mice was measured by a thickness gauge,and the spleen and lymph nodes of mice were taken to observe the changes.HE and toluidine blue staining were used to observe the inflammatory cells and mast cell infiltration in mice.Flow cytometry was used to detect the levels of IL-4 and TNF-α in the lymph nodes of mice,and enzyme-linked immunosorbent was used to determine the levels of IL-4,TNF-α and IgE in serum of mice,and the expression of IL-4,IL-5 and IL-13 in the supernatant of HaCaT cells.Western blot was used to detect the expression of P-Ezrin and Ezrin in skin tissues.Results Celastrol significantly inhibited the swelling of ear and back skin tissues,reduced the de-granulation of inflammatory cells and mast cells,low-ered serum IgE and serum and lymph node levels of IL-4 and TNF-α,and reduced the activation of Ezrin in mice,and the expression of IL-4,IL-5 and IL-13 in the supernatant of HaCaT cells was restored by the treat-ment with Ezrin siRNA.Conclusion Celastrol amel-iorates AD,which may be achieved by modulating Ezrin activation.

Objective To explore astrocyte activation's impact on cognitive deficits post-traumatic brain injury(TBI).Methods SPF male rats were divided into control,sham-operation and model groups with 10 rats per group.Control group did not receive the surgical intervention;sham-operation group underwent craniotomy without damaging the dura mater;model group was struck with brain injury instrument after craniotomy.The rats with knockout overexpressed glial fibrillary acidic protein(GF AP)gene were set as the knockout group and overexpression group,with 10 rats per group.The knockout and overexpression groups were treated as the model group.Neurological function was evaluated by modified neurological severity score(mNSS).Escape latency was assessed with the Morris water maze test.The expression levels of GFAP in astrocytes were measured quantitative real-time polymerase chain reaction.The positive expression of astrocytes was determined by immunohistochemistry.Results The mNSS of control,sham-operation,model,knockout and overexpression groups were 0,0,(9.60±1.17),(15.20±1.55)and(12.00±1.33)points;the escape latency period at day 7 was(16.15±2.48),(16.98±2.35),(40.72±5.42),(75.42±8.59)and(47.23±6.04)s;the number of positive astrocytes was(1 264.60±135.45),(1 289.20±132.29),(3 269.10±189.39),(103.90±11.09)and(5 301.50±236.29)cell·mm-2;the expression levels of GFAP gene in control,sham-operation,model and overexpression groups were 0.86±0.02,0.92±0.04,1.37±0.07 and 3.42±0.07.Compared with overexpression group,the differences of above indexes in control,sham-operation,model,knockout groups were statistically significant(all P＜0.05).Conclusion TBI causes cognitive impairment and affects cognition and memory in rats,and the GFAP gene is associated with the activation of astrocytes and helps repair nerve damage.

Objective To explore astrocyte activation's impact on cognitive deficits post-traumatic brain injury(TBI).Methods SPF male rats were divided into control,sham-operation and model groups with 10 rats per group.Control group did not receive the surgical intervention;sham-operation group underwent craniotomy without damaging the dura mater;model group was struck with brain injury instrument after craniotomy.The rats with knockout overexpressed glial fibrillary acidic protein(GF AP)gene were set as the knockout group and overexpression group,with 10 rats per group.The knockout and overexpression groups were treated as the model group.Neurological function was evaluated by modified neurological severity score(mNSS).Escape latency was assessed with the Morris water maze test.The expression levels of GFAP in astrocytes were measured quantitative real-time polymerase chain reaction.The positive expression of astrocytes was determined by immunohistochemistry.Results The mNSS of control,sham-operation,model,knockout and overexpression groups were 0,0,(9.60±1.17),(15.20±1.55)and(12.00±1.33)points;the escape latency period at day 7 was(16.15±2.48),(16.98±2.35),(40.72±5.42),(75.42±8.59)and(47.23±6.04)s;the number of positive astrocytes was(1 264.60±135.45),(1 289.20±132.29),(3 269.10±189.39),(103.90±11.09)and(5 301.50±236.29)cell·mm-2;the expression levels of GFAP gene in control,sham-operation,model and overexpression groups were 0.86±0.02,0.92±0.04,1.37±0.07 and 3.42±0.07.Compared with overexpression group,the differences of above indexes in control,sham-operation,model,knockout groups were statistically significant(all P＜0.05).Conclusion TBI causes cognitive impairment and affects cognition and memory in rats,and the GFAP gene is associated with the activation of astrocytes and helps repair nerve damage.