Objective To compare the therapeutic efficacy and identify differences between haploidentical hematopoietic stem cell transplantation combined with mesenchymal stem cells (Haplo-MSC) and umbilical cord blood hematopoietic stem cell transplantation combined with mesenchymal stem cells (UCB-MSC) in mice with bone marrow acute radiation syndrome (ARS). Methods Eight-to ten-week-old CB6F1 mice were exposed to 8 Gy of ⁶⁰Co γ-ray irradiation to establish a bone marrow-type ARS model.The mice were then randomly assigned to three groups: the Haplo-MSC group (haploidentical hematopoietic stem cells combined with MSCs), the UCB-MSC group (umbilical cord blood stem cells combined with MSCs), and a saline control group. The survival rate, peripheral blood cell counts, pathological changes in target organs, colony formation of bone marrow cells, and graft-versus-host disease (GVHD) were observed. Results All mice in the saline control group died within 14 days, with a median survival time of 8.9 days. The 30 day survival rate was 65% in the Haplo-MSC group and 60% in the UCB-MSC group. The Log-rank test showed no significant difference in survival time between the two transplantation groups (P=0.561). At 28 days post-transplantation, no significant differences were observed in WBC, PLT, RBC, or Hb counts between the two groups (P=0.151, 0.733, 0.856, and 0.300, respectively). Pathological changes in bone marrow cells showed that bone marrow failure occurred later in the UCB-MSC group than in the Haplo-MSC group. In contrast, the Haplo-MSC group exhibited faster hematopoietic stem cell engraftment. Furthermore, the numbers of CFU-E, CFU-GM, and CFU-GEMM differed significantly between the two groups (P<0.05). Conclusion Both the Haplo-MSC and UCB-MSC regimens promoted hematopoietic engraftment and reconstitution in mice with lethal-dose radiation-induced bone marrow ARS. However, the onset of bone marrow failure was delayed in mice treated with the UCB-MSC regimen. In contrast, mice treated with the Haplo-MSC regimen showed faster engraftment.

Objective:To systematically retrieve and summarize the best available evidence on aerobic exercise combined with resistance training in stroke patients.Methods:Using a structured computer-assisted search strategy based on the "6S" model, literature was retrieved top-down from clinical decision support systems, guideline databases, professional society websites, evidence-based databases, and comprehensive databases. The search included literature related to aerobic and resistance training in stroke patients, including clinical decision tools, guidelines, recommended practices, evidence summaries, systematic reviews, expert consensus documents, and randomized controlled trials (RCT) . The search was performed from the inception of each database to February 28, 2025. Two researchers independently screened the literature, assessed quality, and extracted and synthesized the evidence.Results:A total of 21 publications were included: nine guidelines, three systematic reviews, one expert consensus, and eight RCTs. A total of 32 best evidence statements were summarized across 12 dimensions: timing of training initiation, training methods, training modes, intensity formulation strategies, training dosage, rest intervals, progression principles, progression strategies, training effects, individualized modifications, safety, and adherence management.Conclusions:This study systematically identified and summarized best-practice evidence for aerobic and resistance training in stroke patients. The findings provide strong evidence-based support for developing tailored and effective exercise interventions in stroke rehabilitation.

Objective To compare differences in the pharmacological activities of Angelica sinensis and its components on hematopoietic and laxative effects.Methods Kunming mice were randomly divided into eight groups,with 12 mice in each group consisting of equal numbers of males and females.These groups included a normal group,a model group,a positive group,a Angelica sinensis(AS)group,an Angelica sinensis water-soluble(AW)group,an Ethanol extract of Angelicae sinensis(AE)group,and an Angelica sinensis essential oil(AO)group.Except for the normal group,all other groups were established as blood deficiency constipation mouse models through subcutaneous injection of N-acetylphenylhydrazine combined with oral administration of loperamide hydrochloride.On the 7th day of modeling,each group received oral administration of the respective test substance once daily for three consecutive days.General condition and body weight changes of the mice were observed,peripheral blood cells were counted,stool morphology and fecal output were recorded,fecal moisture content and colonic tissue moisture content were determined,small intestine propulsion rate was assessed by a charcoal meal method,and serum levels of β-endorphin(β-EP),cholecystokinin octapeptide(CCK-8),substance P(SP),and vasoactive intestinal peptide(VIP)were determined by ELISA.Differences in the pharmacological activities of Angelica sinensis and its components on hematopoietic and laxative effects were analyzed.Results Compared with the normal group,model group mice showed significantly reduced white blood cell(WBC),red blood cell(RBC),hemoglobin(HGB),hematocrit(HCT),and platelet(PLT)counts,and body weight(P＜0.05 or P＜0.01).Additionally,fecal moisture content,colon moisture content,and small intestine propulsion rate were decreased(P＜0.05 or P＜0.01)and serum CCK-8 and SP levels were also lower(P＜0.01),while serum β-EP and VIP levels increased(P＜0.05).Compared with the model group,AS and AW groups had higher WBC,RBC,HGB,HCT,and PLT counts,defecation volume,fecal moisture content,and colon moisture content(P＜0.05 or P＜0.01).The AE group showed increased WBC,RBC,HGB,HCT,and PLT counts,and colon moisture content(P＜0.05 or P＜0.01),but defecation volume and fecal moisture content were not significantly altered.The AO group exhibited increased fecal moisture content,colon moisture content,and defecation volume(P＜0.05 or P＜0.01),but no significant changes in WBC,RBC,HGB,HCT,and PLT counts.The AE group showed no significant changes in defecation volume,fecal moisture content,and colon moisture content.The AS and AO groups had increased small intestine propulsion rates(P＜0.01),while there was no significant difference in small intestine propulsion rate between the AW and AE groups.The AS group had elevated serum CCK-8 and SP levels(P＜0.01)and decreased serum β-EP and VIP levels(P＜0.01).The AO group had increased serum CCK-8 and SP levels(P＜0.05),but no significant change in serum β-EP and VIP levels.The AW group had decreased serum VIP levels(P＜0.05),but no statistically significant difference in serum CCK-8 and SP levels.Compared with the AS group,the AW group had higher WBC,RBC,HGB,HCT,and PLT counts,while the AO and AE groups had lower levels of these parameters(P＜0.05).Both AW and AO groups had increased fecal moisture content(P＜0.05),and both AW and AE groups had increased colon moisture content(P＜0.05).AO,AE,and AW groups had elevated serum CCK-8 and SP levels and decreased serum β-EP and VIP levels(P＜0.05).In summary,the groups were ordered as follows:AE＞AO＞AS＞AW in terms of blood replenishment,AO＞AS＞AW＞AE in terms of promoting bowel movements,and AO＞AS＞AE＞AW in terms of intestinal motility.Conclusions Angelica sinensis and its components have varying degrees of blood replenishing and bowel-promoting activities.The AE component has strong blood replenishing activity,while the AO component has strong bowel-promoting and defecation-stimulating activity.These findings provide a reference for the development of traditional Chinese medicines based on Angelica sinensis components.

Objective : To investigate the protective effect of dimethyl fumarate(DMF) on maternal intrahepatic cholestasis(ICP) during pregnancy induced by di(2-ethylhexyl) phthalate(DEHP) exposure and its mechanism. Methods : Thirty-two 8-week-old female institute of cancer research(ICR) mice were randomly divided into 4 groups: Ctrl group, DEHP group, DMF group and DEHP+DMF group. DEHP and DEHP+DMF groups were treated with DEHP(200 mg/kg) by gavage every morning at 9:00 a.m. DMF and DEHP+DMF groups were treated with DMF(150 mg/kg) from day 13 to day 16 of gestation by gavage. After completion of gavage on day 16 of pregnancy, maternal blood, maternal liver, placenta, and amniotic fluid were collected from pregnant mice after a six-hour abrosia. The body weight of the mother rats and the body weight of the fetus rats were sorted and analyzed; the levels of total bile acid(TBA), alkaline phosphatase(ALP), aspartate aminotransferase/alanine aminotransferase(AST/ALT) in serum and TBA in liver, amniotic fluid and placenta were detected by biochemical analyzer; HE staining was used to observe the pathological changes of liver tissue; Quantitative reverse transcription PCR(RT-qPCR) was used to detect the expression levels of tumor necrosis factor-α(TNF-α), interleukin(IL)-6, IL-1, IL-18 and NOD-like receptor thermal protein domain associated protein 3(NLRP3) in the liver; Western blot was used to detect the expression of the nuclear factor KappaB(NF-κB) and NLRP3. Results : Compared with the control group, the body weight of the DEHP-treated dams and pups decreased(P<0.05); the levels of TBA, ALP, AST/ALT in the serum of dams and the levels of TBA in the liver, amniotic fluid, and placenta of dams increased(P<0.05); the histopathological results showed that liver tissue was damaged, bile ducts were deformed, and there was inflammatory cell infiltration around them; the levels of inflammation-related factors TNF-α, IL-6, IL-1, IL-18 and NLRP3 transcription in maternal liver increased(P<0.05); the expression of NF-κB and NLRP3 protein in maternal liver significantly increased( P<0. 05). Compared with the DEHP group,the body weight of both dams and fetuses significantly increased in DEHP + DMF group( P<0. 05); the levels of TBA,ALP,AST/ALT in the serum of dams and amniotic fluid of fetuses decreased( P<0. 05); the degree of liver lesions was improved; the transcription levels of inflammation-related factors TNF-α,IL-6,IL-1,IL-18 and NLRP3 in maternal liver decreased( P<0. 05); the expression of NF-κB and NLRP3 protein in maternal liver significantly decreased( P<0. 05). Conclusion DMF can effectively protect the DEHP exposure to lead to female ICP,and its mechanism may be through inhibiting the NF-κB/NLRP3 pathway and reducing liver inflammation.

Temporomandibular joint osteoarthritis (TMJ-OA) is a common disease often accompanied by pain, seriously affecting physical and mental health of patients. Abnormal innervation at the osteochondral junction has been considered as a predominant origin of arthralgia, while the specific mechanism mediating pain remains unclear. To investigate the underlying mechanism of TMJ-OA pain, an abnormal joint loading model was used to induce TMJ-OA pain. We found that during the development of TMJ-OA, the increased innervation of sympathetic nerve of subchondral bone precedes that of sensory nerves. Furthermore, these two types of nerves are spatially closely associated. Additionally, it was discovered that activation of sympathetic neural signals promotes osteoarthritic pain in mice, whereas blocking these signals effectively alleviates pain. In vitro experiments also confirmed that norepinephrine released by sympathetic neurons promotes the activation and axonal growth of sensory neurons. Moreover, we also discovered that through releasing norepinephrine, regional sympathetic nerves of subchondral bone were found to regulate growth and activation of local sensory nerves synergistically with other pain regulators. This study identified the role of regional sympathetic nerves in mediating pain in TMJ-OA. It sheds light on a new mechanism of abnormal innervation at the osteochondral junction and the regional crosstalk between peripheral nerves, providing a potential target for treating TMJ-OA pain.
Animals ; Osteoarthritis/physiopathology* ; Mice ; Sympathetic Nervous System/physiopathology* ; Temporomandibular Joint Disorders/physiopathology* ; Arthralgia ; Sensory Receptor Cells ; Disease Models, Animal ; Norepinephrine ; Male ; Temporomandibular Joint/physiopathology* ; Pain Measurement

Objective To compare differences in the pharmacological activities of Angelica sinensis and its components on hematopoietic and laxative effects.Methods Kunming mice were randomly divided into eight groups,with 12 mice in each group consisting of equal numbers of males and females.These groups included a normal group,a model group,a positive group,a Angelica sinensis(AS)group,an Angelica sinensis water-soluble(AW)group,an Ethanol extract of Angelicae sinensis(AE)group,and an Angelica sinensis essential oil(AO)group.Except for the normal group,all other groups were established as blood deficiency constipation mouse models through subcutaneous injection of N-acetylphenylhydrazine combined with oral administration of loperamide hydrochloride.On the 7th day of modeling,each group received oral administration of the respective test substance once daily for three consecutive days.General condition and body weight changes of the mice were observed,peripheral blood cells were counted,stool morphology and fecal output were recorded,fecal moisture content and colonic tissue moisture content were determined,small intestine propulsion rate was assessed by a charcoal meal method,and serum levels of β-endorphin(β-EP),cholecystokinin octapeptide(CCK-8),substance P(SP),and vasoactive intestinal peptide(VIP)were determined by ELISA.Differences in the pharmacological activities of Angelica sinensis and its components on hematopoietic and laxative effects were analyzed.Results Compared with the normal group,model group mice showed significantly reduced white blood cell(WBC),red blood cell(RBC),hemoglobin(HGB),hematocrit(HCT),and platelet(PLT)counts,and body weight(P＜0.05 or P＜0.01).Additionally,fecal moisture content,colon moisture content,and small intestine propulsion rate were decreased(P＜0.05 or P＜0.01)and serum CCK-8 and SP levels were also lower(P＜0.01),while serum β-EP and VIP levels increased(P＜0.05).Compared with the model group,AS and AW groups had higher WBC,RBC,HGB,HCT,and PLT counts,defecation volume,fecal moisture content,and colon moisture content(P＜0.05 or P＜0.01).The AE group showed increased WBC,RBC,HGB,HCT,and PLT counts,and colon moisture content(P＜0.05 or P＜0.01),but defecation volume and fecal moisture content were not significantly altered.The AO group exhibited increased fecal moisture content,colon moisture content,and defecation volume(P＜0.05 or P＜0.01),but no significant changes in WBC,RBC,HGB,HCT,and PLT counts.The AE group showed no significant changes in defecation volume,fecal moisture content,and colon moisture content.The AS and AO groups had increased small intestine propulsion rates(P＜0.01),while there was no significant difference in small intestine propulsion rate between the AW and AE groups.The AS group had elevated serum CCK-8 and SP levels(P＜0.01)and decreased serum β-EP and VIP levels(P＜0.01).The AO group had increased serum CCK-8 and SP levels(P＜0.05),but no significant change in serum β-EP and VIP levels.The AW group had decreased serum VIP levels(P＜0.05),but no statistically significant difference in serum CCK-8 and SP levels.Compared with the AS group,the AW group had higher WBC,RBC,HGB,HCT,and PLT counts,while the AO and AE groups had lower levels of these parameters(P＜0.05).Both AW and AO groups had increased fecal moisture content(P＜0.05),and both AW and AE groups had increased colon moisture content(P＜0.05).AO,AE,and AW groups had elevated serum CCK-8 and SP levels and decreased serum β-EP and VIP levels(P＜0.05).In summary,the groups were ordered as follows:AE＞AO＞AS＞AW in terms of blood replenishment,AO＞AS＞AW＞AE in terms of promoting bowel movements,and AO＞AS＞AE＞AW in terms of intestinal motility.Conclusions Angelica sinensis and its components have varying degrees of blood replenishing and bowel-promoting activities.The AE component has strong blood replenishing activity,while the AO component has strong bowel-promoting and defecation-stimulating activity.These findings provide a reference for the development of traditional Chinese medicines based on Angelica sinensis components.

Objective : To establish a method for measuring major organic acids in the tricarboxylic acid cycle using a high-performance liquid chromatography-tandem mass spectrometry(HPLC-MS/MS) system, and to investigate the changes in six tricarboxylic acid cycle organic acids(fumaric acid, malic acid, succinic acid, α-ketoglutaric acid, cis-aconitic acid, and citric acid) in the serum, liver, and placenta of mice exposed to di(2-ethylhexyl) phthalate(DEHP) during pregnancy. Methods : The serum, liver and placental samples from pregnant mice were processed and eluted through a Waters ACQUITY UPLC BEH Amide Column(130 Å, 1.7 μm, 2.1 mm × 150 mm) using a gradient elution program. Mobile phase A comprised an aqueous solution of 10 mmol/L ammonium acetate and 5 μmol/L methanephosphonic acid, while mobile phase B consisted of a 90% acetonitrile aqueous solution containing 10 mmol/L ammonium acetate and 5 μmol/L methanephosphonic acid, with a flow rate maintained at 0.35 ml/min. The mass spectrometry detection system utilized an electrospray ionization technique with negative ion mode for multiple reaction monitoring. Results : The correlation coefficients of the standard curves for the six tricarboxylic acid cycle organic acid metabolites were all above 0.996 within the quantitative range. The method's accuracy ranged from 97.14% to 108.26%, with inter-day and intra-day precision relative standard deviation between 1.35% and 6.73%. The matrix effect was between 93.29% and 107.47%, and the extraction recovery rate ranged from 94.82% to 112.57%. Analysis of six tricarboxylic acid cycle organic acids in the liver, serum, and placenta of DEHP-exposed mice during pregnancy showed significant reductions in fumaric acid, malic acid, α-ketoglutaric acid, cis-aconitic acid, and citric acid compared to the control group(P<0.05). Conclusion The HPLC-MS/MS method established in this study for detecting six tricarboxylic acid cycle organic acids in the serum, liver, and placenta of DEHP-exposed pregnant mice is stable, highly sensitive and selective. Prenatal DEHP exposure induced alterations in the levels of tricarboxylic acid(TCA) cycle organic acid metabolites in the liver, serum, and placenta of mice, suggesting that DEHP exposure during pregnancy may interfere with mitochondrial TCA cycle processes. These findings indicate potential value in the diagnosis and treatment of diseases associated with prenatal DEHP exposure.

Objective:To investigate the association between peak growth hormone(GH) levels and body fat mass as well as body fat percentage in children with short stature.Methods:This retrospective study included 477 children diagnosed with short stature at the Affiliated Hospital of Jining Medical University between January 2021 and November 2024, based on data from the Growth and Development Disease Follow-up Cohort Study(GDDSD) in Shandong Province. Clinical data including anthropometric measurements, laboratory tests, and body composition were collected. The relationship between GH peak and body fat mass and percentage were analyzed using smooth curve fitting and multiple piecewise linear regression models.Results:In univariate linear regression analysis, both body fat mass and body fat percentage were positively correlated with age, height, weight, body mass index, triglycerides, low density lipoprotein-cholesterol, fasting blood glucose, total body water, protein, and skeletal muscle mass(all P<0.05), and negatively correlated with GH peak and high density lipoprotein-cholesterol. After adjusting for potential confounding factors, a nonlinear relationship was observed between GH peak and both body fat mass and body fat percentage, with inflection points at 6.80 ng/mL and 7.75 ng/mL, respectively. When GH peak was below the inflection point, it was significantly negatively correlated with body fat mass and percentage( P<0.001). However, when GH peak exceeded the inflection point, the associations were no longer statistically significant( P>0.05). Conclusions:This study demonstrates a nonlinear relationship between peak GH levels and body fat percentage in children with short stature. At lower GH peaks, both body fat mass and body fat percentage increase significantly, which may contribute to an elevated future risk of cardiovascular disease.

Objective:To systematically retrieve and summarize the best available evidence on aerobic exercise combined with resistance training in stroke patients.Methods:Using a structured computer-assisted search strategy based on the "6S" model, literature was retrieved top-down from clinical decision support systems, guideline databases, professional society websites, evidence-based databases, and comprehensive databases. The search included literature related to aerobic and resistance training in stroke patients, including clinical decision tools, guidelines, recommended practices, evidence summaries, systematic reviews, expert consensus documents, and randomized controlled trials (RCT) . The search was performed from the inception of each database to February 28, 2025. Two researchers independently screened the literature, assessed quality, and extracted and synthesized the evidence.Results:A total of 21 publications were included: nine guidelines, three systematic reviews, one expert consensus, and eight RCTs. A total of 32 best evidence statements were summarized across 12 dimensions: timing of training initiation, training methods, training modes, intensity formulation strategies, training dosage, rest intervals, progression principles, progression strategies, training effects, individualized modifications, safety, and adherence management.Conclusions:This study systematically identified and summarized best-practice evidence for aerobic and resistance training in stroke patients. The findings provide strong evidence-based support for developing tailored and effective exercise interventions in stroke rehabilitation.

Objective:To investigate the association between peak growth hormone(GH) levels and body fat mass as well as body fat percentage in children with short stature.Methods:This retrospective study included 477 children diagnosed with short stature at the Affiliated Hospital of Jining Medical University between January 2021 and November 2024, based on data from the Growth and Development Disease Follow-up Cohort Study(GDDSD) in Shandong Province. Clinical data including anthropometric measurements, laboratory tests, and body composition were collected. The relationship between GH peak and body fat mass and percentage were analyzed using smooth curve fitting and multiple piecewise linear regression models.Results:In univariate linear regression analysis, both body fat mass and body fat percentage were positively correlated with age, height, weight, body mass index, triglycerides, low density lipoprotein-cholesterol, fasting blood glucose, total body water, protein, and skeletal muscle mass(all P<0.05), and negatively correlated with GH peak and high density lipoprotein-cholesterol. After adjusting for potential confounding factors, a nonlinear relationship was observed between GH peak and both body fat mass and body fat percentage, with inflection points at 6.80 ng/mL and 7.75 ng/mL, respectively. When GH peak was below the inflection point, it was significantly negatively correlated with body fat mass and percentage( P<0.001). However, when GH peak exceeded the inflection point, the associations were no longer statistically significant( P>0.05). Conclusions:This study demonstrates a nonlinear relationship between peak GH levels and body fat percentage in children with short stature. At lower GH peaks, both body fat mass and body fat percentage increase significantly, which may contribute to an elevated future risk of cardiovascular disease.