Objective:To investigate the clinical features and therapeutic efficacy of patients with hereditary leiomyomatosis and renal cell carcinoma(RCC) syndrome-associated RCC (HLRCC-RCC) in China.Methods:The clinical data of 119 HLRCC-RCC patients with fumarate hydratase (FH) germline mutation confirmed by genetic diagnosis from 15 medical centers nationwide from January 2008 to December 2021 were retrospectively analyzed. Among them, 73 were male and 46 were female. The median age was 38(13, 74) years. The median tumor diameter was 6.5 (1.0, 20.5) cm. There were 38 cases (31.9%) in stage Ⅰ-Ⅱand 81 cases (68.1%) in stage Ⅲ-Ⅳ. In this group, only 11 of 119 HLRCC-RCC patients presented with skin smooth muscle tumors, and 44 of 46 female HLRCC-RCC patients had a history of uterine fibroids. The pathological characteristics, treatment methods, prognosis and survival of the patients were summarized.Results:A total of 86 patients underwent surgical treatment, including 70 cases of radical nephrectomy, 5 cases of partial nephrectomy, and 11 cases of reductive nephrectomy. The other 33 patients with newly diagnosed metastasis underwent renal puncture biopsy. The results of genetic testing showed that 94 patients had FH gene point mutation, 18 had FH gene insertion/deletion mutation, 4 had FH gene splicing mutation, 2 had FH gene large fragment deletion and 1 had FH gene copy number mutation. Immunohistochemical staining showed strong 2-succinocysteine (2-SC) positive and FH negative in 113 patients. A total of 102 patients received systematic treatment, including 44 newly diagnosed patients with metastasis and 58 patients with postoperative metastasis. Among them, 33 patients were treated with tyrosine kinase inhibitor (TKI) combined with immune checkpoint inhibitor (ICI), 8 patients were treated with bevacizumab combined with erlotinib, and 61 patients were treated with TKI monotherapy. Survival analysis showed that the median progression-free survival (PFS) of TKI combined with ICI was 18 (5, 38) months, and the median overall survival (OS) was not reached. The median PFS and OS were 12 (5, 14) months and 30 (10, 32) months in the bevacizumab combined with erlotinib treatment group, respectively. The median PFS and OS were 10 (3, 64) months and 44 (10, 74) months in the TKI monotherapy group, respectively. PFS ( P=0.009) and OS ( P=0.006) in TKI combined with ICI group were better than those in bevacizumab combined with erlotinib group. The median PFS ( P=0.003) and median OS ( P=0.028) in TKI combined with ICI group were better than those in TKI monotherapy group. Conclusions:HLRCC-RCC is rare but has a high degree of malignancy, poor prognosis and familial genetic characteristics. Immunohistochemical staining with strong positive 2-SC and negative FH can provide an important basis for clinical diagnosis. Genetic detection of FH gene germ line mutation can confirm the diagnosis. The preliminary study results confirmed that TKI combined with ICI had a good clinical effect, but it needs to be confirmed by the results of a large sample multi-center randomized controlled clinical study.

Objective:The purpose of quantitatively evaluating policies related to clinical specialties and exploring existing policy problems and paths to optimization is to provide a reference basis for the formulation and improvement of the policies.Methods:Text mining was conducted on the policies related to clinical specialties issued by the national and some provincial governments since the new medical reform in 2009.The PMC index model was used to construct a comprehensive evaluation system of policies containing 9 primary variables and 35 secondary variables.22 clinical specialty policies were selected for quantitative analysis.Results:Among the 22 clinical specialty policies,6 policies were good-type policies,14 were acceptable-type policies,2 were bad-type policies,and there were no excellent-type policies.The overall design of the policies related to clinical specialties is reasonable,but there is still room for improvement.Conclusion:The quality of China's clinical specialty policy text needs to be improved,and it is necessary to strengthen the top-level design,optimise the content of the objectives,focus on the balanced and sustainable development of the speciality,give full play to the role of demand-based policy tools,and enrich the incentives and constraints,in order to mobilise multi-principal participation in the construction of the clinical speciality enthusiasm.

OBJECTIVE: To compare clinical efficacy between anatomical locking plate (ALP) and ordinary steel plate (OSP) in treating closed calcaneal fractures with SandersⅡ and Ⅲ. METHODS: From May 2016 to May 2018, 68 patients with closed Sanders typeⅡ and Ⅲ calcaneal fractures were retrospectively analyzed, and were divided into anatomical locking plate group (ALP group) and ordinary steel plate group (OSP group) according to two kinds of plate fixation, and 34 patients in each group. In ALP group, there were 21 males and 13 females aged from 20 to 63 years old with average of (35.16±8.45) years old; 14 patients were typeⅡand 20 patients were type Ⅲaccording to Sanders classification;treated with ALP. In OSP group, there were 20 males and 14 females aged from 19 to 63 years old with average of (35.05±8.39) years old;19 patients were typeⅡand 15 patients were type Ⅲ according to Sanders classification;treated with OSP. Operative time, intraoperative blood loss and complications between two groups were observed and compared;preoperative and postoperative Böhler angle and gissane angle were also compared;American Orthopaedic Foot & Ankle Society (AOFAS) ankle and hind foot scores, foot and ankle disability index (FADI) scores were applied to evaluate clinical effect. RESULTS: All patients were followed up from 11 to 14 months with an average of (12.06±0.81) months. There were no statistical differences in opertive time, intraoperative blood loss, incision infection and refracture rate in complications between two groups ( CONCLUSION Compared with OSP, ALP in treating SandersⅡ and Ⅲ calcaneal fractures could achieve better therapeutic effect, avoid screw loosening, reduce complications, and improve limb function in further.
Adult ; Ankle Joint ; Calcaneus/surgery* ; Case-Control Studies ; Female ; Fracture Fixation, Internal ; Fractures, Bone/surgery* ; Humans ; Lower Extremity ; Male ; Middle Aged ; Retrospective Studies ; Steel ; Treatment Outcome ; Young Adult

BACKGROUND: Innovative coronavirus disease 2019 (COVID-19) vaccines, with elevated global manufacturing capacity, enhanced safety and efficacy, simplified dosing regimens, and distribution that is less cold chain-dependent, are still global imperatives for tackling the ongoing pandemic. A previous phase I trial indicated that the recombinant COVID-19 vaccine (V-01), which contains a fusion protein (IFN-PADRE-RBD-Fc dimer) as its antigen, is safe and well tolerated, capable of inducing rapid and robust immune responses, and warranted further testing in additional clinical trials. Herein, we aimed to assess the immunogenicity and safety of V-01, providing rationales of appropriate dose regimen for further efficacy study. METHODS: A randomized, double-blind, placebo-controlled phase II clinical trial was initiated at the Gaozhou Municipal Centre for Disease Control and Prevention (Guangdong, China) in March 2021. Both younger (n = 440; 18-59 years of age) and older (n = 440; ≥60 years of age) adult participants in this trial were sequentially recruited into two distinct groups: two-dose regimen group in which participants were randomized either to follow a 10 or 25 μg of V-01 or placebo given intramuscularly 21 days apart (allocation ratio, 3:3:1, n = 120, 120, 40 for each regimen, respectively), or one-dose regimen groups in which participants were randomized either to receive a single injection of 50 μg of V-01 or placebo (allocation ratio, 3:1, n = 120, 40, respectively). The primary immunogenicity endpoints were the geometric mean titers of neutralizing antibodies against live severe acute respiratory syndrome coronavirus 2, and specific binding antibodies to the receptor binding domain (RBD). The primary safety endpoint evaluation was the frequencies and percentages of overall adverse events (AEs) within 30 days after full immunization. RESULTS: V-01 provoked substantial immune responses in the two-dose group, achieving encouragingly high titers of neutralizing antibody and anti-RBD immunoglobulin, which peaked at day 35 (161.9 [95% confidence interval [CI]: 133.3-196.7] and 149.3 [95%CI: 123.9-179.9] in 10 and 25 μg V-01 group of younger adults, respectively; 111.6 [95%CI: 89.6-139.1] and 111.1 [95%CI: 89.2-138.4] in 10 and 25 μg V-01 group of older adults, respectively), and remained high at day 49 after a day-21 second dose; these levels significantly exceed those in convalescent serum from symptomatic COVID-19 patients (53.6, 95%CI: 31.3-91.7). Our preliminary data show that V-01 is safe and well tolerated, with reactogenicity predominantly being absent or mild in severity and only one vaccine-related grade 3 or worse AE being observed within 30 days. The older adult participants demonstrated a more favorable safety profile compared with those in the younger adult group: with AEs percentages of 19.2%, 25.8%, 17.5% in older adults vs. 34.2%, 23.3%, 26.7% in younger adults at the 10, 25 μg V-01 two-dose group, and 50 μg V-01 one-dose group, respectively. CONCLUSIONS: The vaccine candidate V-01 appears to be safe and immunogenic. The preliminary findings support the advancement of the two-dose, 10 μg V-01 regimen to a phase III trial for a large-scale population-based evaluation of safety and efficacy. TRIAL REGISTRATION http://www.chictr.org.cn/index.aspx (No. ChiCTR2100045107, http://www.chictr.org.cn/showproj.aspx?proj=124702).
Aged ; Antibodies, Viral ; COVID-19/therapy* ; COVID-19 Vaccines ; Double-Blind Method ; Humans ; Immunization, Passive ; Recombinant Fusion Proteins ; SARS-CoV-2

We report in this study the identification of a natural product-like antagonist () of Vps34 as a potent autophagy modulator structure-based virtual screening. Aurone derivative strongly inhibited Vps34 activity in cell-free and cell-based assays. Significantly, prevents autophagy in human cells induced either by starvation or by an mTOR inhibitor. modeling and kinetic data revealed that could function as an ATP-competitive inhibitor of Vps34. Moreover, it suppressed autophagy and without inducing heart or liver damage in mice. could be utilized as a new motif for more selective and efficacious antagonists of Vps34 for the potential treatment of autophagy-related human diseases.

OBJECTIVETo analyze the complications of percutaneous kyphoplasty except bone leakge for the treatment of osteoporotic thoracolumbar vertebral compression fractures.

METHODSFrom October 2008 to October 2012,178 patients with 224 osteoporotic vertebral compression fractures were treated with percutaneous kyphoplasty under local anethsia. There were 72 males and 106 females,ranging in age from 58 to 92 years old,with an average of 75.3 years,including 93 thoracic vertebrae and 131 lumbar vertebrae. The complications except bone cement leakage were analyzed during operation and after operation.

RESULTSAll operations were successful and all patients were followed up from 12 to 60 months with an average of 26.2 months. No death was found. Bone cement leakage occurred in 27 cases, about 15.1% in 178 cases; and complications except bone cement leakage occurred in 15 cases. There was 1 case with cardiac arrest,was completely recovery by cardiopulmonary resuscitation (CPR) immediately; and 1 case with temporary absence of breathing,was recovery after treatment. There were 3 cases with fall of blood pressure and slower of heart rate; 1 case with intestinal obstruction; 2 cases with local hematoma and 1 case with intercostal neuralgia. Vertebral body fractures of 2 cases were split by bone cement and the fractures of adjacent body occurred in 4 cases.

CONCLUSIONIt's uncommon complication except bone cement leakge in treatment of osteoporotic thoracolumbar vertebral compression fractures with percutaneous kyphoplasty. The complication of cardiopulmonary system is a high risk in surgery; and cytotoxicity of bone cement,nervous reflex,fat embolism and alteration of intravertebral pressure may be main reasons.

Aged ; Aged, 80 and over ; Female ; Fractures, Compression ; surgery ; Humans ; Kyphoplasty ; adverse effects ; Lumbar Vertebrae ; injuries ; surgery ; Male ; Middle Aged ; Osteoporotic Fractures ; surgery ; Postoperative Complications ; etiology ; Spinal Fractures ; surgery ; Thoracic Vertebrae ; injuries ; surgery

OBJECTIVETo evaluate the clinical outcomes of percutaneous kyphoplasty (PKP) in treating senile osteoporotic vertebral compression fractures under local anesthesia.

METHODSFrom May 2007 to May 2010,129 patients with osteoporotic vertebral compression fractures were treated with PKP under local anesthesia. There were 47 males and 82 females, ranging in age from 61 to 92 years old,with an average of 73.7 years old,including 88 segments of thoracic vertebrae and 101 segments of lumbar vertebrae. Visual analogue scale (VAS),height of vertebral body,Cobb's angle were evaluated before and after operation.

RESULTSOperations were performed successfully in all patients and these patients were followed up from 24 to 60 months with an average of 34.2 months. Preoperative,postoperative two weeks and at final follow-up,VAS score was 7.9+/-2.5,2.8+/-1.8,3.0+/-2.2,respectively;Cobb angle was (28.3+/-13.7)degree, (16.2+/-9.8)degree, (19.1+/-10.3)degree, respectively. There was significant difference between postoperative and preoperative, and between at final follow up and preoperative (P<0.05). The height of vertebral body obtained partial recovery. Bone cement leakage occurred in 23 vertebrae (with proportion of 17.8%) during operation,among one patient with temporary clinical symptom of radiculalgia. All lumbago obtained obviously anesis after operation, 1 case complicated with respiratory depression and recovered after resuscitation; 1 case complicated with intestinal obstruction and improved after treatment, 1 case complicated with fracture separation of vertebral body by bone cement, and 4 cases complicated with fracture of adjacent vertebral body.

CONCLUSIONPercutaneous vertebral kyphoplasty is an effective method for treatment of senile osteoporotic vertebral compression fractures,which can expeditiously relieve pain and effectively recovery height of vertebral body and Cobb angle,it has advantages of minimal invasive. The results of short and mid-term follow-up were satisfactory, long-term follow-up is still needed. Correctly choosing the operative indication and improving surgical technique may avoid complications, especially bone cement leakage which is the most frequent complication.

Aged ; Aged, 80 and over ; Anesthesia, Local ; methods ; Female ; Follow-Up Studies ; Fractures, Compression ; surgery ; Humans ; Kyphoplasty ; adverse effects ; methods ; Male ; Middle Aged ; Osteoporotic Fractures ; surgery ; Spinal Fractures ; surgery

BACKGROUNDDetection of coronary microembolization is of clinical importance for patient management and prediction of long-term outcome. However, there are few studies of the changes of magnetic resonance imaging after coronary microembolization. This study was designed to investigate the imaging of the left ventricle using delayed contrast enhanced magnetic resonance imaging as well as the left ventricular ejection fraction after coronary microembolization in animal models.

METHODSEight miniswine, of either sex (body weight 21-25 kg), were used to make the coronary microembolization model. After coronary angiography, a 2.8F infusion catheter was placed in the left anterior descending artery with the tip located between the second and third diagonal branches. Microspheres with the diameter of 42 microm and mean dosage of 1.2 x 10(5) were selectively infused into the left anterior descending artery. First pass and stressed first pass perfusion scan were performed after cine images were acquired. Then a second bolus of 0.15 mmol/kg gadolinium DTPA was given at a rate of 2 ml/s. Ten minutes later, delayed contrast enhanced magnetic resonance images of the left ventricular wall were evaluated. Serum changes of tumor necrosis factor alpha (TNF-alpha) were evaluated by enzyme-linked immunosorbent assay (ELISA).

RESULTSHypoenhancement was not observed at first pass perfusion at the anterior wall of the left ventricle. Hyperenhancements of the anterior-septal and anterior wall of the left ventricle was in evidence on delayed enhancement images 6 hours after microembolization and disappeared one week later. The characteristic change of coronary microembolization on delayed contrast enhanced magnetic imaging was non-enhanced regions within the hyperenhancement zone. Left ventricular ejection fraction measured by magnetic resonance imaging decreased significantly from 0.451 +/- 0.063 at baseline to 0.362 +/- 0.070 at the sixth hour (P < 0.01), and recovered to 0.431 +/- 0.053 one week later (P < 0.01 vs 6th hour). Compared with baseline values, the left ventricular end systolic volume enlarged significantly at 6th hour and at one week after microembolization (P < 0.05 and P < 0.01 respectively). Serum TNF-alpha increased significantly at 6th hour (22.62 +/- 6.96) pg/ml compared with baseline (16.83 +/- 3.45) pg/ml (P < 0.05) and it further increased to (27.44 +/- 3.97) pg/ml at one week after coronary microembolization and was significantly higher than that at baseline (P < 0.01).

CONCLUSIONSOn delayed contrast enhanced magnetic resonance imaging, hyperenhancement of the anterior-septal and anterior wall of the left ventricle show at 6th hour but not at one week after coronary microembolization. This might represent the characteristic imaging after coronary microembolization. The left ventricular ejection fraction decreased at 6th hour and recovered one week later after coronary microembolization. Although impairment of left ventricular function could be recovered at 1 week after coronary microembolization, the left ventricular remodeling process still continued in concert with continuously elevation of serum TNF-alpha.

Animals ; Contrast Media ; Coronary Angiography ; Embolization, Therapeutic ; methods ; Female ; Hemodynamics ; Image Enhancement ; methods ; Magnetic Resonance Imaging ; methods ; Male ; Swine ; Ventricular Function, Left

OBJECTIVETo explore the feasibility of magnetic resonance imaging (MR) on detecting transplanted nanometer small superparamagnetic iron oxides (SPIO) labeled mesenchymal stem cells (MSCs) in swine model with acute myocardial infarction (MI).

METHODSMSCs isolated from swine were incubated with nanometer SPIO for 24 hours and the third-passage MSCs were labeled with DNA dye 4'-6-diamidino-2-phenylindole (DAPI) and aliphatic red fluorescent dye PKH(26)-GL. Presence of small particles of SPIO in MSCs was assessed by Prussian Blue staining and electron microscopy. Three animals in each group received SPIO-labeled MSCs (5 x 10(5); 1 x 10(6); 2 x 10(6)) and MSCs without SPIO (1 x 10(6)) injections into the infarcted myocardium approximately 1 hour following left anterior descending coronary artery. MRI (1.5-T) was performed 20 to 24 hours post infarction in all animals and the animals were subsequently sacrificed for histology 1 hour post MRI.

RESULTSIn vitro Prussian Blue staining and electron microscopy examination revealed numerous iron particles in the cytoplasm of MSCs. Low signal intensity spots with the scanning T(2)(*)WI-Flash 2d sequence were detected in all SPIO-MSCs but not in SPIO-negative-MSCs injected myocardial sites in vivo with the clinical 1.5 T scanner. Prussian blue, DAPI and PKH(26) positive cells were detected histologically in sections corresponding to low signal intensity spots area shown on MRI.

CONCLUSIONMagnetically labeled MSCs transplanted in myocardial ischemia area of swine can be visualized in vivo with a clinical 1.5-T MRI and could be used for tracking SPIO-MSCs clinically.

Animals ; Biomarkers ; Disease Models, Animal ; Ferrosoferric Oxide ; Magnetic Resonance Imaging ; methods ; Mesenchymal Stem Cell Transplantation ; Mesenchymal Stromal Cells ; cytology ; Myocardial Infarction ; pathology ; surgery ; Myocytes, Cardiac ; Nanoparticles ; Swine

0.05). In the HBsAg stimulus group,the proliferation activity of CD4+ CD25- T cells from HBV transgenic mice was significantly lower than that in normal mice (P0.05). In all the 2 groups,the proliferation activity of CD4+ CD25- T cells alone from HBV transgenic mice or normal mice was significantly higher than that mixed culturing (P