Lingguizhugan Decoction (LGZG) demonstrates significant efficacy in treating various cardiovascular diseases clinically, yet its precise mechanism of action remains elusive. This study aimed to elucidate the potential mechanisms and effects of LGZG on isoproterenol (ISO) continuous stimulation-induced chronic heart failure (CHF) in mice, providing direct experimental evidence for further clinical applications. In vivo, continuous ISO infusion was administered to mice, and ventricular myocytes were utilized to explore LGZG?s potential mechanism of action on the ?1-adrenergic receptor (?1-AR)/Gs/G protein-coupled receptor kinases (GRKs)/?-arrestin signaling deflection system in the heart. The findings reveal that LGZG significantly reduced the messenger ribonucleic acid (mRNA) expression of hypertrophy-related biomarkers [atrial natriuretic peptide (ANP) and B-type natriuretic peptide (BNP)] and improved cardiac remodeling and left ventricular diastolic function in mice with ISO-induced CHF. Furthermore, LGZG inhibited the overactivation of Gs/cyclic adenosine monophosphate (cAMP)/protein kinase A (PKA) signaling and downregulated the downstream transcriptional activity of cAMP-response element binding protein (CREB) and the expression of the coactivator CBP/P300. Notably, LGZG downregulated the expression of ?-arrestin1 and GRK 2/3/5 while upregulating the expression of ?1-AR and ?-arrestin2. These results suggest that LGZG inhibits Gs/cAMP/PKA signaling and ?-arrestin/GRK-mediated desensitization and internalization of ?1-AR, potentially exerting cardioprotective effects through the synergistic regulation of the ?1-AR/Gs/GRKs/?-arrestin signaling deflection system via multiple pathways.
Animals ; Heart Failure/genetics* ; Signal Transduction/drug effects* ; Drugs, Chinese Herbal/pharmacology* ; Mice ; Male ; G-Protein-Coupled Receptor Kinases/genetics* ; Mice, Inbred C57BL ; Humans ; Isoproterenol ; Arrestins/genetics* ; Chronic Disease

Tumor metastasis is the leading cause of high mortality in most cancers, and numerous studies have demonstrated that the malignant crosstalk of multiple components in the tumor microenvironment (TME) together promotes tumor metastasis. Cancer-associated fibroblasts (CAFs) are the major stromal cells and crosstalk centers in the TME of various kinds of tumors, such as breast cancer, pancreatic cancer, and prostate cancer. Recently, the CAF-induced pro-tumor metastatic TME has gained wide attention, being considered as one of the effective targets for tumor therapy. With in-depth research, CAFs have been found to promote tumor metastasis through multiple mechanisms, such as inducing epithelial-mesenchymal transition in tumor cells, remodeling the extracellular matrix, protecting circulating tumor cells, and facilitating the formation of a pre-metastatic niche. To enhance the anti-tumor metastasis effect, therapeutic strategies designed by combining nano-drug delivery systems with CAF modulation are undoubtedly a desirable choice, as evidenced by the research over the past decades. Herein, we introduce the physiological properties of CAFs, detail the possible mechanisms whereby CAFs promote tumor metastasis, categorize CAFs-based nano-drug delivery strategies according to their anti-metastasis functions and discuss the current challenges, possible solutions, as well as the future directions in order to provide a theoretical basis and reference for the utilization of CAFs-based nano-drug delivery strategies to promote tumor metastasis therapy.

OBJECTIVE To observe the clinical efficacy of Yijinjing in the treatment of elderly sarcopenia and its effect on chro-nic inflammatory response in patients,and to explore the Yijinjing exercise prescription suitable for elderly patients with sarcopenia.METHODS A total of 120 elderly patients with sarcopenia admitted to the Department of Rehabilitation Medicine,Suzhou Hospital of Traditional Chinese Medicine from September 2022 to September 2024 were selected and randomly divided into a control group and a Yijinjing group,with 60 cases in each group.The control group received health education and dietary guidance,and the Yijinjing group received Yijinjing exercises on the basis of the intervention of the control group.The changes in skeletal muscle mass,upper and lower limb muscle strength,muscle thickness,muscle cross-sectional area,physical fitness and chronic inflammation level were observed in the two groups before and after the intervention.RESULTS After intervention,the skeletal muscle mass,grip strength,30 s sit-stand test times,rectus femoris thickness and cross-sectional area,vastus intermedius thickness,and physical fit-ness assessment of the patients in the Yijinjing group were significantly increased compared with those before treatment(P<0.05),and the indicators after intervention were higher than those in the control group(P<0.05);the serum TNF-α and IL-18 levels in the Yi-jinjing group were significantly decreased compared with those before treatment(P<0.05),and the indicators after intervention were lower than those in the control group(P<0.05);there was no statistically significant change in the biceps brachii thickness and serum IL-6 level in the Yijinjing group compared with those before treatment(P>0.05);there was no significant correlation between the bi-ceps brachii thickness and grip strength after Yijinjing intervention,r=0.139 8,P>0.05;there was a significant negative correlation between the TNF-α level and grip strength after Yijinjing intervention,r=-0.313 8,P<0.05.CONCLUSION Yijinjing exercises can improve muscle mass and strength in elderly patients with sarcopenia,and improve the physical fitness of patients,which may be related to improving the chronic inflammatory state of the body.

Objective:To investigate the clinical experience and efficacy of unrelated umbilical cord blood hematopoietic stem cell transplantation (HSCT) for the treatment of congenital amegakaryocytic thrombocytopenia (CAMT).Methods:A case summary was conducted.The clinical data of 2 children with CAMT who were finally cured by unrelated umbilical cord blood HSCT in the Department of Pediatric Medicine, the First Affiliated Hospital of Zhengzhou University from March 2020 to August 2023 were retrospectively analyzed.Related studies were retrieved from databases CNKI, Wanfang and PubMed using search terms including " congenital amegakaryocytic thrombocytopenia" and " hematopoietic stem cell transplantation" from the inception to July 2024.The clinical characteristics, diagnosis and treatment processes, and prognosis of CAMT patients treated by HSCT were then summarized.Results:Both cases exhibited scattered skin haemorrhages throughout the body and carried 2 compound heterozygous mutations with pathogenicity in the MPL gene.Both patients were finally diagnosed with CAMT.Case 1 was a girl aged 3 at the time of transplantation, and case 2 was also a girl, who aged 5 at the time of transplantation.Both of them received unrelated umbilical cord blood HSCT and hematopoietic reconstruction was achieved.The time of neutrophil and platelet implantation was 21 and 40 days after transplantation in case 1, and 20 and 31 days in case 2, respectively.The chimerism rate of neutrophil implantation in both children was complete chimerism of donor cells.Implantation syndrome was detected in case 1 following transplantation.Case 2 suffered implantation syndrome, hypertensive encephalopathy, and cytomegalovirus infection following transplantation.Both children showed no graft-versus-host disease (GVHD).Both children had hematopoietic and immune reconstruction after transplantation and their primary diseases were cured.Cases 1 and 2 were followed up for more than 14 and 17 months, respectively.Both of them achieved disease-free survival during the follow up.Literature review of 26 cases with CAMT treated by HSCT, including the above-mentioned 2 cases was conducted, with an overall disease-free survival rate of 92.3%(24/26).Of 12 cases with CAMT typing, 10 were type Ⅰ and 2 were type Ⅱ.Of the 26 cases treated by HSCT, 17 had bone marrow HSCT, with an overall survival rate of 88.2%(15/17), and 2 had peripheral blood HSCT.Seven cases had umbilical cord blood HSCT (6 cases receiving unrelated umbilical cord blood HSCT and 1 case receiving related umbilical cord blood HSCT), with an overall survival rate of 100%.Unlike bone marrow and peripheral blood HSCT, unrelated umbilical cord blood HSCT did not result in 3-4 grade GVHD. Conclusions:Unrelated umbilical cord blood HSCT can achieve good therapeutic effects in CAMT patients when there is no suitable donor.Myeloablative pretreatment is conducive to CAMT patients.

OBJECTIVE To observe the clinical efficacy of Yijinjing in the treatment of elderly sarcopenia and its effect on chro-nic inflammatory response in patients,and to explore the Yijinjing exercise prescription suitable for elderly patients with sarcopenia.METHODS A total of 120 elderly patients with sarcopenia admitted to the Department of Rehabilitation Medicine,Suzhou Hospital of Traditional Chinese Medicine from September 2022 to September 2024 were selected and randomly divided into a control group and a Yijinjing group,with 60 cases in each group.The control group received health education and dietary guidance,and the Yijinjing group received Yijinjing exercises on the basis of the intervention of the control group.The changes in skeletal muscle mass,upper and lower limb muscle strength,muscle thickness,muscle cross-sectional area,physical fitness and chronic inflammation level were observed in the two groups before and after the intervention.RESULTS After intervention,the skeletal muscle mass,grip strength,30 s sit-stand test times,rectus femoris thickness and cross-sectional area,vastus intermedius thickness,and physical fit-ness assessment of the patients in the Yijinjing group were significantly increased compared with those before treatment(P<0.05),and the indicators after intervention were higher than those in the control group(P<0.05);the serum TNF-α and IL-18 levels in the Yi-jinjing group were significantly decreased compared with those before treatment(P<0.05),and the indicators after intervention were lower than those in the control group(P<0.05);there was no statistically significant change in the biceps brachii thickness and serum IL-6 level in the Yijinjing group compared with those before treatment(P>0.05);there was no significant correlation between the bi-ceps brachii thickness and grip strength after Yijinjing intervention,r=0.139 8,P>0.05;there was a significant negative correlation between the TNF-α level and grip strength after Yijinjing intervention,r=-0.313 8,P<0.05.CONCLUSION Yijinjing exercises can improve muscle mass and strength in elderly patients with sarcopenia,and improve the physical fitness of patients,which may be related to improving the chronic inflammatory state of the body.

Objective:To investigate the clinical experience and efficacy of unrelated umbilical cord blood hematopoietic stem cell transplantation (HSCT) for the treatment of congenital amegakaryocytic thrombocytopenia (CAMT).Methods:A case summary was conducted.The clinical data of 2 children with CAMT who were finally cured by unrelated umbilical cord blood HSCT in the Department of Pediatric Medicine, the First Affiliated Hospital of Zhengzhou University from March 2020 to August 2023 were retrospectively analyzed.Related studies were retrieved from databases CNKI, Wanfang and PubMed using search terms including " congenital amegakaryocytic thrombocytopenia" and " hematopoietic stem cell transplantation" from the inception to July 2024.The clinical characteristics, diagnosis and treatment processes, and prognosis of CAMT patients treated by HSCT were then summarized.Results:Both cases exhibited scattered skin haemorrhages throughout the body and carried 2 compound heterozygous mutations with pathogenicity in the MPL gene.Both patients were finally diagnosed with CAMT.Case 1 was a girl aged 3 at the time of transplantation, and case 2 was also a girl, who aged 5 at the time of transplantation.Both of them received unrelated umbilical cord blood HSCT and hematopoietic reconstruction was achieved.The time of neutrophil and platelet implantation was 21 and 40 days after transplantation in case 1, and 20 and 31 days in case 2, respectively.The chimerism rate of neutrophil implantation in both children was complete chimerism of donor cells.Implantation syndrome was detected in case 1 following transplantation.Case 2 suffered implantation syndrome, hypertensive encephalopathy, and cytomegalovirus infection following transplantation.Both children showed no graft-versus-host disease (GVHD).Both children had hematopoietic and immune reconstruction after transplantation and their primary diseases were cured.Cases 1 and 2 were followed up for more than 14 and 17 months, respectively.Both of them achieved disease-free survival during the follow up.Literature review of 26 cases with CAMT treated by HSCT, including the above-mentioned 2 cases was conducted, with an overall disease-free survival rate of 92.3%(24/26).Of 12 cases with CAMT typing, 10 were type Ⅰ and 2 were type Ⅱ.Of the 26 cases treated by HSCT, 17 had bone marrow HSCT, with an overall survival rate of 88.2%(15/17), and 2 had peripheral blood HSCT.Seven cases had umbilical cord blood HSCT (6 cases receiving unrelated umbilical cord blood HSCT and 1 case receiving related umbilical cord blood HSCT), with an overall survival rate of 100%.Unlike bone marrow and peripheral blood HSCT, unrelated umbilical cord blood HSCT did not result in 3-4 grade GVHD. Conclusions:Unrelated umbilical cord blood HSCT can achieve good therapeutic effects in CAMT patients when there is no suitable donor.Myeloablative pretreatment is conducive to CAMT patients.

Objective:To analyze the effect of Iron deficiency anemia (IDA) and Black stain (BS) on the microbial community of dental plaque.Methods:A total of 136 preschool children aged 3 to 6 years old from 12 kindergartens in Shinan District and Shibei District of Qingdao City were investigated by using a cluster sampling method from April to May 2019. They were divided into two groups based on oral examination: the early childhood caries (ECC) group and the caries-free (CF) group. According to whether they had IDA and BS, they were further divided into four groups: the IDA with caries (IDA-ECC) group, the non-IDA with caries (NIDA-ECC) group, the BS without caries (BS-CF) group and the non-BS without caries (NBS-CF) group. The gingival plaque of the study subjects was collected. The 16S rRNA gene was sequenced by using Illumina MiSeq high-throughput sequencing technology. The composition, community structure and different bacteria genera of the microbial communities between the groups were compared and analyzed. Potential biomarkers within each group were further identified by linear discriminant analysis of effect size (LEfSe).Results:The 136 children were aged (5.11±0.87) years old, with 80 boys (58.82%). There were statistically significant differences in the microbial composition, structure and function of oral plaque between the ECC and CF groups ( P<0.05). There were statistically significant differences in the microbial richness and diversity of oral plaque between the IDA-ECC and NIDA-ECC groups ( P<0.05). There was no significant difference in microbial diversity index between the BS-CF and NBS-CF groups ( P>0.05). The LEfSe analysis results showed that 41, 31 and 9 taxa with different relative abundance were identified between the ECC and CF groups, IDA-ECC and NIDA-ECC groups, and BS-CF and NBS-CF groups, respectively. Conclusion:IDA and BS have an effect on the microecological diversity and microbial community function of oral plaque in young children with early childhood caries.

Objective To investigate preliminary clinical effects of three-dimensional(3D)printing combined with minimally invasive percutaneous plate osteosynthesis(MIPPO)in the treatment of anterior pelvic ring injuries.Methods Between December 2017 and July 2023,we treated 15 patients with anterior pelvic ring injuries by using 3D printing combined with MIPPO.Before surgery,a 3D model was printed to establish the actual structure,and a steel plate was pre-bent outside the body to simulate the surgery,as well as the design of number,direction,and length of screws.Then,the pre-bent internal fixation device was inserted through the bone membrane tunnel in the anterior pelvic ring,and the screws were fixed through both sides of the incision according to the preoperative planning.Results All the 15 patients underwent surgery successfully without complications such as nerve and vascular injury.The operation time was(162.9±63.1)min,the total length of incision was(13.5±2.2)cm,the number of fluoroscopic examinations during the surgery was(5.5±1.0)times,and the amount of blood loss was(456.7±272.5)ml.The fracture healing time was(17.5±1.8)weeks.The 15 patients were followed up for(15.2±3.9)months.The Majeed functional score increased significantly from(18.3±2.3)points before surgery to(86.3±6.0)points at 6 months postoperatively(t=-47.313,P=0.000).The fracture reduction according to the Matta standards showed excellent in 14 patients,fair in one patient,the excellent and good rate being 93.3％(14/15).Conclusion Combination of 3D printing and MIPPO treatment for anterior pelvic ring injuries can achieve good clinical effects.

Objective:To analyze the effect of Iron deficiency anemia (IDA) and Black stain (BS) on the microbial community of dental plaque.Methods:A total of 136 preschool children aged 3 to 6 years old from 12 kindergartens in Shinan District and Shibei District of Qingdao City were investigated by using a cluster sampling method from April to May 2019. They were divided into two groups based on oral examination: the early childhood caries (ECC) group and the caries-free (CF) group. According to whether they had IDA and BS, they were further divided into four groups: the IDA with caries (IDA-ECC) group, the non-IDA with caries (NIDA-ECC) group, the BS without caries (BS-CF) group and the non-BS without caries (NBS-CF) group. The gingival plaque of the study subjects was collected. The 16S rRNA gene was sequenced by using Illumina MiSeq high-throughput sequencing technology. The composition, community structure and different bacteria genera of the microbial communities between the groups were compared and analyzed. Potential biomarkers within each group were further identified by linear discriminant analysis of effect size (LEfSe).Results:The 136 children were aged (5.11±0.87) years old, with 80 boys (58.82%). There were statistically significant differences in the microbial composition, structure and function of oral plaque between the ECC and CF groups ( P<0.05). There were statistically significant differences in the microbial richness and diversity of oral plaque between the IDA-ECC and NIDA-ECC groups ( P<0.05). There was no significant difference in microbial diversity index between the BS-CF and NBS-CF groups ( P>0.05). The LEfSe analysis results showed that 41, 31 and 9 taxa with different relative abundance were identified between the ECC and CF groups, IDA-ECC and NIDA-ECC groups, and BS-CF and NBS-CF groups, respectively. Conclusion:IDA and BS have an effect on the microecological diversity and microbial community function of oral plaque in young children with early childhood caries.

Objective To investigate preliminary clinical effects of three-dimensional(3D)printing combined with minimally invasive percutaneous plate osteosynthesis(MIPPO)in the treatment of anterior pelvic ring injuries.Methods Between December 2017 and July 2023,we treated 15 patients with anterior pelvic ring injuries by using 3D printing combined with MIPPO.Before surgery,a 3D model was printed to establish the actual structure,and a steel plate was pre-bent outside the body to simulate the surgery,as well as the design of number,direction,and length of screws.Then,the pre-bent internal fixation device was inserted through the bone membrane tunnel in the anterior pelvic ring,and the screws were fixed through both sides of the incision according to the preoperative planning.Results All the 15 patients underwent surgery successfully without complications such as nerve and vascular injury.The operation time was(162.9±63.1)min,the total length of incision was(13.5±2.2)cm,the number of fluoroscopic examinations during the surgery was(5.5±1.0)times,and the amount of blood loss was(456.7±272.5)ml.The fracture healing time was(17.5±1.8)weeks.The 15 patients were followed up for(15.2±3.9)months.The Majeed functional score increased significantly from(18.3±2.3)points before surgery to(86.3±6.0)points at 6 months postoperatively(t=-47.313,P=0.000).The fracture reduction according to the Matta standards showed excellent in 14 patients,fair in one patient,the excellent and good rate being 93.3％(14/15).Conclusion Combination of 3D printing and MIPPO treatment for anterior pelvic ring injuries can achieve good clinical effects.