Local focal adhesion kinase (FAK) is a non-receptor intracellular tyrosine kinase that plays an important role in tumor initiation, development, metastasis and invasion, and is considered to be an important target for the development of antineoplastic drugs. It has both kinase-dependent and non-kinase-dependent scaffolding functions. However, traditional small molecular inhibitors can only inhibit its kinase-dependent activity, so it is difficult to target the kinase-independent scaffolding function. Therefore, there is an urgent need for novel strategies to enhance FAK targeting to lay the foundation for determining the druggability and discovery of FAK inhibitors. Proteolysis targeting chimera (PROTAC) is a new drug development strategy that can recruit E3 ligase to specifically ubiquitinylate target proteins for degradation through the proteasome system. The unique mechanism of action of the PROTAC system could be used to target and degrade the FAK protein, thus eliminating the scaffolding function of FAK. In this review, FAK protein, the signaling pathway, and small molecule inhibitors are briefly described, and the latest research progress in targeting the degradation of FAK using PROTAC technology is summarized.

OBJECTIVETo test the effect of intramyocardial injection of autologous bone marrow mononuclear cells (MNCs) in improving the cardiac function and myocardial revascularization in miniswine models of myocardial infarction.

METHODSThe miniswine models of myocardial infarction established by ligation of the anterior descending coronary artery were divided into 3 groups including a control and two MNC injection groups. Autologous bone marrow MNCs were injected via the epicardium into the infarcted area in the latter two groups at 1 and 2 weeks after the infarction, respectively. The ventricular segmental wall motion was evaluated after the treatment, and the infarcted myocardium observed with immunohistochemistry on frozen sections.

RESULTSThe left ventricular segmental wall motion differed significantly between the control and the MNC injection groups at 1 and 2 months after the treatment. CM-DiI-positive cells were detected in the infarcted myocardium where MNCs were implanted.

CONCLUSIONIntramyocardial injection of autologous bone marrow MNCs improves the infarcted ventricular segmental wall motion, and significantly increases the number of blood vessels in the infracted area. The transplanted cells can be integrated into the vascular walls of the capillaries and arterioles and differentiate into cardiomyocytes.

Animals ; Bone Marrow Cells ; cytology ; Bone Marrow Transplantation ; methods ; Disease Models, Animal ; Leukocytes, Mononuclear ; transplantation ; Myocardial Infarction ; pathology ; surgery ; Swine ; Swine, Miniature ; Transplantation, Autologous

The aim of this study was to investigate the circulating levels of IL-11 in the patients with chronic idiopathic thrombocytopenic purpura (CITP), and its significance, and to evaluate the curative effect of rhIL-11 on CITP. The level of IL-11 in patients with CITP was determined by ELISA before and after treatment, respectively. 1.5 mg of rhIL-11 were injected subcutaneously, once a day, continuously for 14 days as one course, treatment time 1 - 2 courses as total. The results showed that the higher blood IL-11 level was found in CITP patients than that in controls (P < 0.01) and during the course of treatment the number of platelets in peripheral blood of patients with CITP parallelled to the level of IL-11. The platelet counts were obviously increased in all CITP patients after rhIL-11 treatment. It is concluded that the serum level of IL-11 in patients is correlated to the number of platelets in patients. rhIL-11 can be used as an effective treatment for CITP.
Adolescent ; Adult ; Aged ; Chronic Disease ; Female ; Humans ; Interleukin-11 ; blood ; therapeutic use ; Male ; Middle Aged ; Platelet Count ; Purpura, Thrombocytopenic, Idiopathic ; drug therapy ; Recombinant Proteins ; therapeutic use ; Treatment Outcome

OBJECTIVETo summarize the experience with surgical treatment of coronary artery disease with severe ischemic mitral valve regurgitation (IMR).

METHODSFrom January 2006 to December 2009, 45 patients (35 males, 10 females aged 32-74 years) with the diagnosis of coronary artery disease complicated by IMR underwent coronary artery bypass grafting (CABG) combined with mitral valve plasty (MVP, 24 cases) or mitral valve replacement (MVR, 21 cases).

RESULTSPerioperative deaths occurred in 2 cases due to multiple organ failure (MOF). Echocardiography showed a significant reduction of the mitral regurgitation area (from 11.80∓2.45 cm(2) to 2.83∓0.98 cm(2), t=22.80, P=0.00) after CABG combined with mitral valve surgery, with also significantly reduced postoperative left ventricular end diastolic diameter (LVEDD) (from 57.61∓10.06 mm to 51.84∓8.98 mm, t=2.85, P=0.005). No significant difference was detected in the left ventricular ejection fraction after the operation [(52.7∓15.4)% vs (53.2∓13.2)%, t=0.16, P=0.87)].

CONCLUSIONSCABG combined with mitral valve surgery can improve early postoperative left ventricular function in patients with ischemic coronary heart disease complicated by severe mitral regurgitation, but further follow-up study is still needed for evaluation of the long-term results.

Adult ; Aged ; Coronary Artery Bypass ; Coronary Disease ; complications ; surgery ; Female ; Humans ; Male ; Middle Aged ; Mitral Valve Insufficiency ; complications ; surgery ; Myocardial Ischemia ; complications ; surgery ; Treatment Outcome

OBJECTIVETo investigate the effects and the related mechanisms of the components of Dang-Gui-Bu-Xue decoction (DGBXD) on improving blood deficiency.

METHODThe effects of promoting hematopoietic function were observed with the blood difficient model mice, by giving components of DGBXD. RBC, WBC, reticulocytes and bone marrow nucleated cells (BMNC) were determined. The components of DGBXD on proliferation of BMNC and on clony forming unit (CFU) were also determined.

RESULTThe components of DGBXD remarkably increased the quantity of RBC, WBC, and BMNC. Some of the components promoted the proliferation of BMNC and increased the quantity of CFU-Mix. Among them, polysaccharide of angelica was most potent.

CONCLUSIONThe studies show that the extracts and some components of DGBXD can promote the hemopoietic function system of the model mice, and they exert the effects in a comprehensive way.

Angelica sinensis ; chemistry ; Animals ; Astragalus membranaceus ; chemistry ; Blood Cell Count ; Bone Marrow Cells ; drug effects ; Colony-Forming Units Assay ; Drug Combinations ; Drugs, Chinese Herbal ; pharmacology ; Female ; Hematopoietic Stem Cells ; drug effects ; Male ; Mice ; Mice, Inbred BALB C ; Mice, Inbred ICR ; Phytotherapy ; Plant Extracts ; pharmacology ; Plants, Medicinal ; chemistry ; Polysaccharides ; isolation & purification ; pharmacology

BACKGROUNDThe delayed diagnosis of pelvi-ureteric junction (PUJ) disruption in children following blunt abdominal trauma can result in loss of function of the involved kidney. We examined the potential for kidney preservation and the limits of diagnostic delays.

METHODSA retrospective review of 17 cases of PUJ disruption at Beijing Children's Hospital from 1993 to 2009 was done with respect to diagnosis, treatment and follow-up.

RESULTSThe interval from trauma to diagnosis of PUJ disruption was (52 ± 52) days. If one case with nephrectomy was excluded, the interval from trauma to diagnosis was (40 ± 20) days. The average time between injury and first treatment was (49 ± 25) days. Pelvi-ureteric reanastomosis and caliceal ureterostomy were performed separately in 11 and 4 patients, respectively. Ileal replacement for ureter injuries was finally performed in one patient. Hydronephrosis of the injured kidney was reduced and the function improved in 15 out of 17 patients (88%). Only one patient received nephrectomy and the nephrectomy rate was 5.9%.

CONCLUSIONDifferential renal function at the PUJ disruption side can be saved and the rate of nephrectomy reduced by appropriate surgery if the time to diagnosis and first treatment is limited to within two months.

Abdominal Injuries ; complications ; surgery ; Child ; Child, Preschool ; Female ; Humans ; Kidney ; injuries ; surgery ; Kidney Pelvis ; injuries ; surgery ; Male ; Retrospective Studies ; Ureter ; injuries ; surgery ; Ureteral Obstruction ; etiology ; surgery

OBJECTIVETo summarize the experience with surgical treatment of constrictive pericarditis.

METHODSA retrospective analysis of the post-operative clinical data was conducted in 128 surgical patients with chronic constrictive pericarditis.

RESULTSTwo early postoperative death occurred in this group due to severe low cardiac output syndrome, with the mortality rate of 1.57%. The postoperative complications included low cardiac output syndrome (13.2%), arrhythmia (7.02%), acute renal insufficiency (3.9%), respiratory insufficiency (3.1%), wound infection (2.3%), postoperative chest bleeding (1.6%) and cerebral infarction (0.78%). Relapse occurred in one case because of incomplete pericardial resection.

CONCLUSIONSConstrictive pericarditis should be confirmed as soon as possible with actively surgery, and the extent of pericardial resection should be decided according to the individual conditions. Complete untethering of the diseased pericardium should be performed with active prevention of postoperative complications.

Adolescent ; Adult ; Aged ; Child ; Child, Preschool ; China ; epidemiology ; Chronic Disease ; Female ; Humans ; Male ; Middle Aged ; Pericarditis, Constrictive ; surgery ; Postoperative Complications ; epidemiology ; Retrospective Studies ; Treatment Outcome ; Young Adult

OBJECTIVETo study the prevalence of different types of neural tube defects (NTDs) in Luliang Prefecture, Shanxi province, where the prevalence of NTDs is unusually high and the correlation between NTDs prevalence and patterns.

METHODSA surveillance population-based birth defects was performed in Luliang Prefecture, Shanxi province.

RESULTSThe results of our study showed that the prevalence of NTDs was 2-fold higher in Luliang Prefecture than in other areas of Shanxi province. Unusual patterns of NTDs were found, however, multiple NTDs were relatively common in Luliang Prefecture, accounting for over 13% of all NTDs cases in China.

CONCLUSIONThe prevalence of NTDs is associated with its patterns.

Child, Preschool ; China ; epidemiology ; Humans ; Infant ; Infant, Newborn ; Neural Tube Defects ; classification ; epidemiology ; Risk Factors

Objective To develop a time-resolved fluorescent immunoassay kit for the rapid,accurate and quantitative detection of S100B protein in serum and to evaluate its performance.Methods The test strip was prepared using time-resolved fluorescent microsphere-labeled anti-S100B polyclonal antibody and rabbit IgG antibody,labeling pads,sample pads,S100B nitrocellulose films and absorbent paper,and an S100B time-resolved fluorescence immunoassay kit was obtained by assembling the cartridge.The performance of the kit developed was evaluated by standard curve,accuracy,minimum detection limit,linear interval,specificity,reproducibility and stability.The reference intervals of 199 pieces of healthy human serum and plasma samples from a certain region were detected with the kit,and the clinical performance of the kit and Roche Elecsys S100 kit was tested by synchronous blind method to assess the consistency of the results of the two kits for 142 samples.Results The S100B time-resolved fluorescence immunoassay kit had the standard curve beingy=(1.133 02+1.752 24)/[1+(x/1.082 20)×(-0.603 52)]-1.752 24,R2=0.999 08 and the linear range being[0.05,30]ng/mL,which met the requirements of the relative deviation of the accuracy within±15％,the minimum detection limit not hgier than 0.05 ng/mL,the relative deviation of specificity within±15％and the coefficient of variation of intra-and inter-batch difference less than 15％.The stability test results indicated that the kit was valid for 12 months at 2-30 ℃ conditions.The reference intervals of serum and plasma samples measured by the kit were both lower than 0.3 ng/mL.Clinical trials showed that the results by the kit and Roche Elecsys S100 Assay Kit were in high agreement(Kappa=0.906 1＞0.80)and met the requirements.Conclusion The kit developed detects the concentration of S100B protein in serum quickly,accurately and quantitatively,and provides references for the diagnosis and treatment of neurological diseases,autoimmune diseases,cerebrovascular diseases and etc.[Chinese Medical Equipment Journal,2024,45(1):47-55]

In the outbreak of COVID-19,triage procedures based on epidemiology were implemented in a local hospital in Changsha to control the transmission of SARS-CoV-2 and avoid healthcare-associated infection.This re-trospective study analyzed the data collected during the triage period and found that COVID-19 patients were en-riched 7 folds into the Section A designated for patients with obvious epidemiological history.On the other side,nearly triple amounts of visits were received at the Section B for patients without obvious epidemiological history.8 COVID-19 cases were spotted out of 247 suspected patients.More than 50％of the suspected patients were submi-tted to multiple rounds of nucleic acid analysis for SARS-CoV-2 infection.Of the 239 patients who were diagnosed as negative of the virus infection,188 were successfully revisited and none was reported as COVID-19 case.Of the 8 COVID-19 patients,3 were confirmed only after multiple rounds of nucleic acid analysis.Besides comorbidities,delayed sharing of epidemiological history added complexity to the diagnosis in practice.The triaging experience and strategy will be helpful for the control of infectious diseases in the future.