The distribution of the ACTH_(1-39)-immunoreactive neurons in the hypotha- lamus of 4 human adults was examined with ABC immunocytochemical method. The results showed that in addition to ACTH_(1-39)-immunoreactive neurons found in the infundibular nucleus of the hypothalamus which were identical with the previous reports, negafivt ACTH_(1-39)immunoreactive neurons were also found in paraventricular and supraoptic nuclei. These cell bodies were round or elliptic in shape. More negative ACTH_(1-39)immunoreactive fibers were seen in the periventricular layer, paraventricular nucleus and dorsal area of supraoptic nucleus.

Object To observe the effect of total flavones isolated from Metasequoia glyptostroboides Hu et Cheng (FMG) on platelet aggregation, 5 HT of release, content of NO in plasma and hemorrheological parameters in rats. Methods Platelet aggregation was quantified by turbidimetry, release of 5 HT was assayed by fluorescence technique, and content of NO in plasma was determined by spectrophotometry. Results Inhibition of platelet aggregation and release of 5 HT, increase of NO content in plasma, as well as decrease of whole blood viscosity, plasma viscosity, red cell electrophoresis time, red cell specific volume, red cell count and K value in ESR equation were observed in the acute blood stasis rat, thereby the rat's hemorrheological properties were improved. Conclusion FMG is able to inhibit the platelet aggregation and improve the hemorrheological parameters in acute blood stasis rat. The inhibition of release of 5 HT, increase of NO content in plasma and antagonistic action of Ca 2+ may be the mechanism of its actions.

Objective To explore the clinical application value of coronary angiography (CAG) combined with fractional flow re-serve(FFR) in percutaneous coronary intervention treatment of coronary artery disease (CAD) .Methods 82 cases of CAD(147 le-sions) with single hemadostenosis at least 70% -90% were randomized into the observation group and the control group .The ob-servation group(40 cases ,72 lesions) was performed the myocardial FFR detection by the pressure guide wire and the drug-eluting stents(DES) were placed in the lesions only if FFR ≤0 .80 .The patients with postoperative FFR ≤0 .80 were given the in-stent post-balloon dilatation .The control group(42 cases ,75 lesions) underwent the percutaneous coronary intervention(PCI) for conduc-ting the routine DES implantation .The general condition ,risk factors(hypertension ,diabetese ,hyperlipidemia ,smoking ,etc .) ,num-ber of lesions ,implanted stents ,hospitalization cost ,occurrence rate of major adverse cardiac events (MACE) after postoperative 6 months and the angina recurrence rate were compared between the two groups .Results The number of used stents per patient and the hospitalization cost in the observation group were significantly lower than those in the control group [(0 .88 ± 0 .88) vs .(1 .81 ± 0 .83) ,(47 200 ± 2 3000)Yuan vs .(60 000 ± 2 4100)Yuan P< 0 .05] .The two groups had no all-cause death in postoperative 6-months .The recurrent myocardial infarction rate ,revascularization rate and recurrent angina in the two groups were 2 .50% vs .0 , 2 .50% vs .2 .38% and 5 .00% vs .7 .14% respectively ,the differences had no statistical significance(P>0 .05) .Conclusion CAG combined with FFR detection can significantly reduce the number of stents and the hospitalization cost without increasing the occur-rence rates of MACE and angina within postoperative 6 months in CAD patients .

Objective:To explore the association between location of lower extremity deep venous thrombosis and incidence of pulmonary embolism in patients with lower extremity fracture during hospitalization.Methods:A retrospective study was conducted of the 1,620 patients who had been treated for lower extremity fracture and deep vein thrombosis from October 2014 to November 2019 at Department of Orthopaedic Trauma, Honghui Hospital. They were 726 males and 894 females, aged from 18 to 98 years (average, 64.0 years). By the anatomical location of thrombosis, they were divided into a proximal thrombosis group and a distal thrombosis group; by the laterality of thrombosis, they were divided into a bilateral thrombosis group and a unilateral thrombosis group which was further divided into a left thrombosis subgroup and a right thrombosis subgroup. The incidences of pulmonary embolism were compared between 2 corresponding groups and subgroups.Results:Pulmonary embolism occurred in 13 of the 1,400 patients with distal thrombosis and in 12 of the 220 patients with proximal thrombosis; the incidence of pulmonary embolism in the proximal thrombosis group (5.45%, 12/220) was significantly higher than that in the distal thrombosis group (0.93%, 13/1,400) ( P<0.001). Pulmonary embolism occurred in 10 of the 337 patients with bilateral thrombosis and in 15 of the 1,283 patients with unilateral thrombosis; the incidence of pulmonary embolism in the bilateral thrombosis subgroup (2.97%, 10/337) was significantly higher than that in the unilateral thrombosis group (1.17%, 15/1,283) ( P=0.017). Pulmonary embolism occurred in 5 of the 677 patients with left thrombosis and in 10 of the 606 patients with right thrombosis; the incidence of pulmonary embolism in the right thrombosis subgroup (1.65%, 10/606) was insignificantly higher than that in the left thrombosis subgroup (0.74%, 5/677) ( P=0.129). Conclusions:In patients with lower extremity fracture, those with proximal or bilateral thrombosis are more prone to pulmonary embolism than those with distal or unilateral thrombosis, but the possibility of pulmonary embolism cannot be ignored clinically in those with distal or unilateral thrombosis.

Objective:To analyze and study the difficulties and countermeasures in the implementation of the Qualified Person(QP) system for stem cell clinical research, and share the experience of QP management practice in our hospital in order to promote and improve the construction of the QP management system in medical institutions.Methods:Comprehensive investigations were conducted to summarize and analyze the shortage of talents, unclear qualifications, unclear responsibilities, and lack of assessment standards in the QP system of medical institutions.Results:In view of the difficulties in the implementation of the current QP system, it is suggested to consider a combination of improving the system of laws and regulations, strengthening the top-level design of stem cell research institutions, clarifying the qualification threshold, refining QP responsibilities, continuing training and assessment system, establishing QP support system, etc.Conclusions:Medical institutions are responsible for stem cell clinical research, and the improvement of the QP system can promote the development of the cell industry in China.

Objective:The study aims to analyze the problems faced in the clinical research and management of stem cells, explore the construction of the entire process of stem cells clinical research, and promote the healthy and orderly development of the clinical research of stem cells.Methods:By consulting the literature and retrieval of relevant policies and regulations, this study analyzed the problems faced by the supervision and management department, medical institutions and researchers, this study and discussed the countermeasures for strengthening the management of the entire process of clinical research of stem cells in medical institutions.Results:There were imperfect internal system and poor management process, insufficient quality control of cell products, low quality of project management, and insufficient clinical research consciousness of stem cell clinical research management in medical institutions.Conclusions:Combined with the current management measures, guidance principles and medical institutions, we should improve the internal system of medical institutions, promote the centralized management and informatization construction of projects, strengthen cell quality control in the hospital, cultivate talent echelons and improve academic and ethical review capabilities, actively explore the management model that is suitable for the entire process of stem cell clinical research for medical institutions in China.

BACKGROUND:Scaffold materials serve as platforms that provide space and structure,playing a crucial role in the regeneration of cartilage tissue.Scholars from around the world are exploring different approaches to fabricate more ideal scaffold materials. OBJECTIVE:To review the design principles and preparation methods of cartilage scaffolds,and to further explore the advantages and limitations of various preparation methods. METHODS:Literature searches were conducted on the databases of CNKI,WanFang Data,PubMed,and FMRS from 1998 to 2023.The search terms were"cartilage repair,cartilage tissue engineering,cartilage scaffold materials,preparation"in Chinese and English.A total of 57 articles were ultimately reviewed. RESULTS AND CONCLUSION:(1)The articular cartilage has a unique structure and limited self-repair capacity after injury.Even if self-repair occurs,the newly formed cartilage is typically fibrocartilage,which is far inferior to normal articular cartilage in terms of structure and mechanical properties.It is difficult to maintain normal function and often leads to degenerative changes.Currently,the design and fabrication of scaffold materials for cartilage repair need to consider the following aspects:biocompatibility and biodegradability,suitable pore structure and porosity,appropriate mechanical properties,and bioactivity.(2)Research on the preparation of cartilage scaffolds has made significant progress,continuously introducing new preparation methods and optimization strategies.These methods have their advantages and disadvantages,providing more possibilities for customized preparation and functional design of cartilage scaffolds according to specific requirements.

BACKGROUND:Bone formation is the process by which osteoblasts synthesize and secrete osteoid and promote its mineralization,which generally involves mechanical signal transduction.Osteoblasts are primarily regulated by mechanical factors such as gravity,compressive stress,tensile stress,fluid shear stress,and hydrostatic pressure in vivo,and different mechanical stimuli modulate the proliferation,differentiation,and apoptosis of osteoblasts through various mechanisms,including hormones,cytoskeletal proteins,and microRNAs.By clarifying the effects of biomechanical forces on osteoblasts,it provides ideas and a reference basis for the treatment of osteometabolic diseases involving osteoblasts. OBJECTIVE:To review the effects of different biomechanical forces on the biological characteristics of osteoblasts. METHODS:We conducted a literature search using PubMed,Web of Science,FMRS,CNKI,and WanFang databases for relevant publications published from 2000 to 2023,covering basic research and tissue engineering studies related to the effects of biomechanical forces on osteoblasts.Ultimately,a total of 70 articles were reviewed. RESULTS AND CONCLUSION:Different biomechanical forces have an impact on the biological characteristics of osteoblasts,including proliferation,differentiation,and apoptosis,and these effects are dependent on the intensity and duration of the applied force.Specifically,the effects are as follows:(1)Under microgravity conditions,osteoblast proliferation and differentiation are inhibited,resulting in a decrease in bone density and the development of osteoporosis.(2)Compared to microgravity,hypergravity has a promoting effect on osteoblast proliferation.(3)The effects of compressive stress on osteoblasts are dependent on the loading intensity and time.Appropriate compressive stress can promote osteoblast proliferation and differentiation,which is beneficial for bone tissue formation and repair,while excessive compressive stress can cause osteoblast apoptosis and bone tissue destruction.(4)The biological effects of different types of tensile stress on osteoblasts differ.Studies have shown that a strain rate within the range of 0-12%has a promoting effect on osteoblast proliferation.(5)Fluid shear stress can promote osteoblast proliferation and differentiation and enhance the bone-inducing effect of biomaterials.(6)Static hydrostatic pressure can affect the biological behavior of osteoblasts,including proliferation,differentiation,and apoptosis,and these effects are closely related to the time and intensity of the pressure.Understanding the effects of different biomechanical forces on osteoblasts is of great significance for a deeper understanding of bone growth and maintenance mechanisms.

Objective To explore the effect of let?7 miRNA silencing on Kaposi′s sarcoma? associated herpesvirus ( KSHV) lytic replication and the underling mechanism. Methods The pEGFP?C2?let?7 sponge vector was transfected into BCBL?1 and 293T cells with Lipofectamine 2000 to silence the expression of let?7 miRNAs. Quantitative real?time PCR ( qRT?PCR) was used to quantify the expression of let?7 miRNAs, the transcriptional levels of mitogen?activated protein kinase kinase kinase kinase 4 ( MAP4K4) , cyclooxygenase?2 ( COX?2) and matrix metalloproteinase 13 ( MMP?13) , and the DNA copy numbers of KSHV open reading frame 50 ( ORF50) and open reading frame 72 ( ORF72) . Western blot was used to detect the total and phosphorylated protein levels of MAP4K4, COX?2, extracellular regulated protein kinases (ERK1/2), c?Jun N?terminal kinase (JNK) and p38 MAPK. Results The expression of let?7 miRNAs was dramatically decreased in the let?7 sponge transfected BCBL?1 and 293T cells compared with that in the vector?transfected cells ( P<0.05 for all) . The gene copy number and mRNA transcriptional level of KSHV ORF50 were significantly increased in the let?7 sponge transfected BCBL?1 cells compared with that in the vector?transfected cells ( 1. 00 ± 0. 10 vs. 2. 33 ± 0. 18 and 1. 08 ± 0. 48 vs 3. 22 ± 0. 27, respectively, P<0.001 for both) . The gene copy number and mRNA transcriptional level of KSHV ORF72 were also significantly increased in let?7 sponge transfected BCBL?1 cells compared with those in the vector?transfected cells(1.07±0.49 vs 1.67±0.45 and 1.01±0.19 vs 1.54±0.11, respectively, P<0.05 for both). Furthermore, the mRNA transcriptional levels of MAP4K4, COX?2 and MMP?13 were significantly increased in the let?7 sponge transfected BCBL?1 cells compared with those in the vector?transfected cells (1.00±0.05 vs 5.73±0.96, 1.00±0.05 vs 2.68±0.19, 1.00±0.02 vs 2.69±0.25, respectively, P<0.001 for all). Let?7 miRNAs silencing also increased the protein expression levels of MAP4K4, COX?2 and phospho?ERK1/2, while the phospho?JNK and phospho?p38 were not changed in the BCBL?1 and 293T cells. Conclusions Let?7 silencing may activate the replication of KSHV, possibly through up?regulating MAP4K4 and its downstream molecules COX?2, MMP?13, and phosphorylation of ERK1/2, finally results in the progression of Kaposi sarcoma.

Objective To explore the effect of let?7 miRNA silencing on Kaposi′s sarcoma? associated herpesvirus ( KSHV) lytic replication and the underling mechanism. Methods The pEGFP?C2?let?7 sponge vector was transfected into BCBL?1 and 293T cells with Lipofectamine 2000 to silence the expression of let?7 miRNAs. Quantitative real?time PCR ( qRT?PCR) was used to quantify the expression of let?7 miRNAs, the transcriptional levels of mitogen?activated protein kinase kinase kinase kinase 4 ( MAP4K4) , cyclooxygenase?2 ( COX?2) and matrix metalloproteinase 13 ( MMP?13) , and the DNA copy numbers of KSHV open reading frame 50 ( ORF50) and open reading frame 72 ( ORF72) . Western blot was used to detect the total and phosphorylated protein levels of MAP4K4, COX?2, extracellular regulated protein kinases (ERK1/2), c?Jun N?terminal kinase (JNK) and p38 MAPK. Results The expression of let?7 miRNAs was dramatically decreased in the let?7 sponge transfected BCBL?1 and 293T cells compared with that in the vector?transfected cells ( P<0.05 for all) . The gene copy number and mRNA transcriptional level of KSHV ORF50 were significantly increased in the let?7 sponge transfected BCBL?1 cells compared with that in the vector?transfected cells ( 1. 00 ± 0. 10 vs. 2. 33 ± 0. 18 and 1. 08 ± 0. 48 vs 3. 22 ± 0. 27, respectively, P<0.001 for both) . The gene copy number and mRNA transcriptional level of KSHV ORF72 were also significantly increased in let?7 sponge transfected BCBL?1 cells compared with those in the vector?transfected cells(1.07±0.49 vs 1.67±0.45 and 1.01±0.19 vs 1.54±0.11, respectively, P<0.05 for both). Furthermore, the mRNA transcriptional levels of MAP4K4, COX?2 and MMP?13 were significantly increased in the let?7 sponge transfected BCBL?1 cells compared with those in the vector?transfected cells (1.00±0.05 vs 5.73±0.96, 1.00±0.05 vs 2.68±0.19, 1.00±0.02 vs 2.69±0.25, respectively, P<0.001 for all). Let?7 miRNAs silencing also increased the protein expression levels of MAP4K4, COX?2 and phospho?ERK1/2, while the phospho?JNK and phospho?p38 were not changed in the BCBL?1 and 293T cells. Conclusions Let?7 silencing may activate the replication of KSHV, possibly through up?regulating MAP4K4 and its downstream molecules COX?2, MMP?13, and phosphorylation of ERK1/2, finally results in the progression of Kaposi sarcoma.