The neonatal mammalian heart has a remarkable regenerative capacity, while the adult heart has difficulty to regenerate. A metabolic reprogramming from glycolysis to fatty acid oxidation occurs along with the loss of cardiomyocyte proliferative capacity shortly after birth. In this study, we sought to determine if and how metabolic reprogramming regulates cardiomyocyte proliferation. Reversing metabolic reprogramming by carnitine palmitoyltransferase 1 (CPT1) inhibition, using cardiac-specific Cpt1a and Cpt1b knockout mice promoted cardiomyocyte proliferation and improved cardiac function post-myocardial infarction. The inhibition of CPT1 is of pharmacological significance because those protective effects were replicated by etomoxir, a CPT1 inhibitor. CPT1 inhibition, by decreasing poly(ADP-ribose) polymerase 1 expression, reduced ADP-ribosylation of dual-specificity phosphatase 1 in cardiomyocytes, leading to decreased p38 MAPK phosphorylation, and stimulation of cardiomyocyte proliferation. Our present study indicates that reversing metabolic reprogramming is an effective strategy to stimulate adult cardiomyocyte proliferation. CPT1 is a potential therapeutic target for promoting heart regeneration and myocardial infarction treatment.

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.

ObjectiveTo establish fingerprint profiles and a quantitative determination method for Lycii Cortex， providing a scientific basis for the formulation of quality standards for Lycii Cortex and its roasted products. MethodsHigh performance liquid chromatography（HPLC） was developed for the quantitative method for determining kukoamine B in Lycii Cortex and its roasted products on an Alphasil XD-C₁₈ CH column（4.6 mm×250 mm， 5 μm）. HPLC fingerprint profiles were established for 10 batches of Lycii Cortex and its roasted products， and ultra-performance liquid chromatography-quadrupole-time-of-flight mass spectrometry（UPLC-Q-TOF-MS） was used to identify the common peaks based on reference standards， literature and MS information. Quality evaluation indicators included yield of decoction pieces， appearance properties， content of kukoamine B， and fingerprint profiles. The temperature and time of the roasting process were investigated to select the optimal preparation process， which was then verified. Additionally， chemical pattern recognition was combined to assess the differences in the chemical composition of Lycii Cortex before and after roasting， as well as among samples from different origins. ResultsQuantitative analysis indicated that the contents of kukoamine B in Lycii Cortex and its roasted products were 0.35%-5.51% and 0.24%-4.15%， respectively. The transfer rate of kukoamine B was 58.6%-78.9% after roasting. The fingerprint profile analysis demonstrated that the method established in this study effectively separated kukoamine B from other components in the samples and distinctly differentiated it from its impurity peak， cis-N-caffeoylputrescine. The HPLC fingerprint profiles of Lycii Cortex and its roasted products showed high similarity（all above 0.95）， with 7 common peaks identified and five common components， including kukoamine B， cis-N-caffeoylputrescine， N-coumaroyl tyramine， feruloyltyramine， and glucosyringic acid， confirmed. Process optimization confirmed that baking at 110 ℃ for 20 min was a stable and feasible method for roasting Lycii Cortex. Principal component analysis and cluster analysis showed that there was little difference in the chemical composition between raw and roasted Lycii Cortex， but the quality of Lycii Cortex from different origins differed greatly. ConclusionThis study successfully established the fingerprint profiles and a quantitative method for the effective component kukoamine B in Lycii Cortex and roasted Lycii Cortex. The qualitative and quantitative analyses clarified that the impact of the roasting process on the chemical composition of Lycii Cortex was less significant than the variations due to its geographical origin. The findings of this study offer a reference for the development of quality evaluation methods and the establishment of quality standards for Lycii Cortex and its processed products.

The paper introduces Professor LIU Xing's clinical experience and characteristics of integrative acupuncture and medication in treatment of primary trigeminal neuralgia (PTN). It is believed that the essential pathogenesis of PTN is pathogenic wind, and qi and blood obstruction results from invasion of pathogenic wind. Hence, dispelling wind is the key principle of treatment. Palpation is done at first in the neck, face and buccal mucosal region to detect the masses in treatment. Acupotomy is operated at the masses distributed at Shangguan (GB3), Xiaguan (ST7) and the white line of buccal mucosa, so as to release masses. Additionally, five-wind points (Fengfu [GV16], bilateral Fengchi [GB20], Yifeng [TE17], Bingfeng [SI12] and Fengmen [BL12]), three-nape points (bilateral Naokong [GB19], Tianzhu [BL10] and Jianjing [GB21]) and three-governor-vessel points (Baihui [GV20], Zhiyang [GV9] and Yintang [GV24⁺]) are selected to dispel wind and stop pain. Besides, herbal decoction (wu feng tang) and blood-letting at ear apex are administered in combination. The integration of acupuncture and medication obtains a holistic effect on PTN by dispelling wind pathogen, and promoting qi and blood circulation.
Humans ; Trigeminal Neuralgia/drug therapy* ; Acupuncture Therapy ; Acupuncture Points ; Female ; Male ; Middle Aged ; Drugs, Chinese Herbal/administration & dosage* ; Combined Modality Therapy ; Adult ; Aged

Objective:To explore the efficacy and safety of olverembatinib in treatment of chronic myeloid leukemia (CML) progressed to acute lymphoblastic leukemia with D241E mutation.Methods:The diagnosis and treatment of a patient with D241E mutant CML progressed to acute lymphoblastic leukemia admitted to the Fourth People's Hospital of Jinan in December 2018 were retrospectively analyzed, and relevant literature was reviewed.Results:The patient was a 47-year-old female, and her blood test result was abnormal during physical examination. She was diagnosed as CML and received treatment with imatinib and dasatinib for 2 years. The disease progressed to philadelphia chromosome (Ph)-positive acute B-lymphoblastic leukemia with BCR-ABL mutation (a D241E mutation). After 3 courses of chemotherapy combined with a targeted drug (ponatinib), the patient achieved complete remission, while the minimal residual disease continued to be positive. The patient received 1 course of chemotherapy combined with olverembatinib from the 4th course of treatment. After olverembatinib monotherapy maintenance therapy for 36 months, the patient achieved molecular complete remission with minimal residual disease. The patient developed complications such as skin pigmentation and elevated lipid levels, but all complications were tolerable.Conclusions:The application of olverembatinib in D241E mutant CML progressed to acute lymphoblastic leukemia can help patients obtain sustained molecular biological remission and good safety.

Objective To investigate the effects of gut microbiota regulation combined with exercise rehabilitation on non-motor symptoms and neurological function in Parkinson's disease patients.Methods A total of 154 Parkinson's disease patients admitted to our hospital from January 2022 to January 2024 were selected as the subjects of the study.Using a random number table,these 154 patients were evenly divided into a control group and a treatment group,with 77 patients in each group.Both groups received standard treatments,but the control group also underwent exercise rehabilitation therapy,while the treatment group received probiotic supplementation and exercise rehabilitation therapy.The effectiveness of the two groups was then compared.Results Following the 12 weeks,24 weeks therapeutic regimen,The treatment group showed significantly better outcomes(P<0.05).Clinically meaningful reductions were observed in Hoehn-Yahr staging,alongside decreased scores on standardized instruments assessing psychiatric symptoms HAMA,HAMD,SCOPA-AUT,UPDRS Ⅰ-IV and PDSS(P<0.05).Concurrently,the study group exhibited enhanced MMSE(P<0.05).Fecal microbiome analyses revealed a favorable ecological shift characterized by increased colonization of beneficial genera Bifidobacterium and Lactobacillus,with concomitant suppression of pathobionts Enterococcus and Enterobacteriaceae.Gait analysis revealed increased step length,speed,and frequency in the treatment group(P<0.05).Conclusion Patients with Parkinson's disease who received probiotics combined with exercise rehabilitation treatment could effectively improve non-motor symptoms and neurological function,while promoting the balance of intestinal flora,and reduce clinical symptoms.

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 effects of gut microbiota regulation combined with exercise rehabilitation on non-motor symptoms and neurological function in Parkinson's disease patients.Methods A total of 154 Parkinson's disease patients admitted to our hospital from January 2022 to January 2024 were selected as the subjects of the study.Using a random number table,these 154 patients were evenly divided into a control group and a treatment group,with 77 patients in each group.Both groups received standard treatments,but the control group also underwent exercise rehabilitation therapy,while the treatment group received probiotic supplementation and exercise rehabilitation therapy.The effectiveness of the two groups was then compared.Results Following the 12 weeks,24 weeks therapeutic regimen,The treatment group showed significantly better outcomes(P<0.05).Clinically meaningful reductions were observed in Hoehn-Yahr staging,alongside decreased scores on standardized instruments assessing psychiatric symptoms HAMA,HAMD,SCOPA-AUT,UPDRS Ⅰ-IV and PDSS(P<0.05).Concurrently,the study group exhibited enhanced MMSE(P<0.05).Fecal microbiome analyses revealed a favorable ecological shift characterized by increased colonization of beneficial genera Bifidobacterium and Lactobacillus,with concomitant suppression of pathobionts Enterococcus and Enterobacteriaceae.Gait analysis revealed increased step length,speed,and frequency in the treatment group(P<0.05).Conclusion Patients with Parkinson's disease who received probiotics combined with exercise rehabilitation treatment could effectively improve non-motor symptoms and neurological function,while promoting the balance of intestinal flora,and reduce clinical symptoms.

To explore the immunomodulatory effects of a new vegetable oil adjuvant(named E515)containing vitamin E(VE)and ginsenosides(GS)on rabbit peripheral blood lymphocytes and Bordetella of rabbit inactivated vaccine.E515,Bordetella bronchiseptica(Bb)and LPS were co-cultured with rabbit peripheral blood lymphocytes in vitro,and the lymphocyte conversion rate was detected by CCK8 method,and the content of lymphocyte supernatant cytokines was detected by ELISA method.After rabbits were immunized with E515-Bb vaccine,the antibody level was detec-ted by indirect ELISA,the serum cytokine content was detected by ELISA,and the protective effect of E515-Bb vaccine on rabbits was observed by challenge test.In vitro cell experiments showed that E515 could significantly increase lymphocyte proliferation and TH1/TH2 cytokine se-cretion in rabbit peripheral blood.In vivo animal experiments showed that E515 adjuvant could sig-nificantly enhance the level of Bb specific antibody induced by Bordetella vaccine in rabbits.In-crease the secretion level of TH1/TH2 cytokines and decrease the secretion level of TNF-α;It can effectively protect rabbits against Bordetella infection with a protection rate of 91.67％.Therefore,E515 as a new vegetable oil adjuvant deserves further study.

To explore the immunomodulatory effects of a new vegetable oil adjuvant(named E515)containing vitamin E(VE)and ginsenosides(GS)on rabbit peripheral blood lymphocytes and Bordetella of rabbit inactivated vaccine.E515,Bordetella bronchiseptica(Bb)and LPS were co-cultured with rabbit peripheral blood lymphocytes in vitro,and the lymphocyte conversion rate was detected by CCK8 method,and the content of lymphocyte supernatant cytokines was detected by ELISA method.After rabbits were immunized with E515-Bb vaccine,the antibody level was detec-ted by indirect ELISA,the serum cytokine content was detected by ELISA,and the protective effect of E515-Bb vaccine on rabbits was observed by challenge test.In vitro cell experiments showed that E515 could significantly increase lymphocyte proliferation and TH1/TH2 cytokine se-cretion in rabbit peripheral blood.In vivo animal experiments showed that E515 adjuvant could sig-nificantly enhance the level of Bb specific antibody induced by Bordetella vaccine in rabbits.In-crease the secretion level of TH1/TH2 cytokines and decrease the secretion level of TNF-α;It can effectively protect rabbits against Bordetella infection with a protection rate of 91.67％.Therefore,E515 as a new vegetable oil adjuvant deserves further study.