Ischemic stroke (IS) is a globally life-threatening disease. Presently, few therapeutic medicines are available for treating IS, and rt-PA is the only drug approved by the US Food and Drug Administration (FDA) in the US. In fact, many agents showing excellent neuroprotection but no blood flow-improving activity in animals have not achieved ideal clinical efficacy, while thrombolytic drugs only improving blood flow without neuroprotection have limited their wider application. To address these challenges and meet the huge unmet clinical need, we have designed and identified a novel compound AAPB with dual effects of neuroprotection and cerebral blood flow improvement. AAPB significantly reduced cerebral infarction and neural function deficit in tMCAO rats, pMCAO rats, and IS rhesus monkeys, as well as displayed exceptional safety profiles and excellent pharmacokinetic properties in rats and dogs. AAPB has now entered phase I of clinical trials fighting IS in China.

The prevalence of Class III malocclusion varies among different countries and regions. The populations from Southeast Asian countries (Chinese and Malaysian) showed the highest prevalence rate of 15.8%, which can seriously affect oral function, facial appearance, and mental health. As anterior crossbite tends to worsen with growth, early orthodontic treatment can harness growth potential to normalize maxillofacial development or reduce skeletal malformation severity, thereby reducing the difficulty and shortening the treatment cycle of later-stage treatment. This is beneficial for the physical and mental growth of children. Therefore, early orthodontic treatment for Class III malocclusion is particularly important. Determining the optimal timing for early orthodontic treatment requires a comprehensive assessment of clinical manifestations, dental age, and skeletal age, and can lead to better results with less effort. Currently, standardized treatment guidelines for early orthodontic treatment of Class III malocclusion are lacking. This review provides a comprehensive summary of the etiology, clinical manifestations, classification, and early orthodontic techniques for Class III malocclusion, along with systematic discussions on selecting early treatment plans. The purpose of this expert consensus is to standardize clinical practices and improve the treatment outcomes of Class III malocclusion through early orthodontic treatment.
Humans ; Malocclusion, Angle Class III/classification* ; Orthodontics, Corrective/methods* ; Consensus ; Child

【Objective】 To perform quantitative analysis on the sample provincial laws and regulations for voluntary blood donation, and provide reference for further revision of laws and regulations. 【Methods】 31 study samples were current provincial laws and regulations for voluntary blood donation that can be collected from open sources. The issue date and the revision date of each sample were recorded. With "The Blood Donation Law of the People’s Republic of China" as reference, 5 categories were formed and additional clauses in samples were coded and rated following content analysis procedures. Sample provinces were divided into two groups based on donation rate and their differences in evaluation scores of categories were examined using rank sum test. 【Results】 Until December, 2021, 31 sample provinces had issued and implemented provincial laws and regulation for voluntary blood donation, and 14 of which had been revised. Many detailed clauses (total score 9.32±3.09) were added in sample provincial laws and regulations, more clauses were added in the categories of 'related government agencies and their responsibilities’, 'management of clinical blood use’ and 'rewards and punishment’. Sample provinces were divided into two groups according to the donation rate per 1 000 people recommended by World Health Organization(10‰). Compared to lower donation rate group, the total score and sub score in the categories of 'basic principles’, 'management of blood collection and supply’ were significantly higher in higher donation rate group. 【Conclusion】 In revision and improvement of provincial laws and regulations, 'basic principles’ and 'management of blood collection and supply’ could be considered. This assay mainly tries to provide a new research perspective and perform quantitative analysis on content of sample provincial laws and regulation for voluntary blood donation, the actual effect of the results in this study need longer time to be examined, and we will keep following its new advances.

Objective:To investigate the influence of effects of transarterial chemoembo-lization (TACE) before liver transplantation on the prognosis of hepatocellular carcinoma.Methods:The retrospective cohort study was conducted. The clinicopathological data of 311 hepatocellular carcinoma patients undergoing TACE before liver transplantation who were admitted to the Third Medical Center of Chinese PLA General Hospital from January 2005 to December 2012 were collec-ted. There were 276 males and 35 females, aged from 47 to 59 years, with a median age of 52 years. All the 311 patients underwent TACE before liver transplantation. Observation indicators: (1) effects of hepatocellular carcinoma patients undergoing TACE and its relationship with clinicopathological factors; (2) follow-up; (3) influencing factors for prognosis of hepatocellular carcinoma patients after liver transplantation. Follow-up was conducted using outpatient examination or telephone interview to detect recurrence and metastasis of tumor and survival and graft loss of patients up to December 2017. The patients were followed up every 2 to 4 weeks within 3 months after liver transplantation, and once every 1 to 3 months thereafter. Measurement data with normal distri-bution were represented as Mean± SD, and comparison between groups was analyzed using the t test. Measurement data with skewed distribution were represented as M(range) or M( Q1, Q3), and comparison between groups was analyzed using the Mann-Whitney U test. Count data were described as absolute numbers or percentages, and comparison between groups was analyzed using the chi-square test. Comparison of ordinal data was analyzed using the nonparametric rank sum test. The COX regression model was used for univariate and multivariate analyses. The Kaplan-Meier method was used to draw survival curves and calculate survival rates, and the Log-rank test was used for survival analysis. Results:(1) Effects of hepatocellular carcinoma patients undergoing TACE and its relationship with clinicopathological factors. Of the 311 patients undergoing TACE, 57 cases had pathologic complete response (pCR) and 254 cases had pathologic partial response (pPR), respectively. Cases with alpha fetoprotein (AFP) <20 μg/L,20?400 μg/L, >400 μg/L, cases with microvascular invasion, cases with tumor number as single nodule, cases with tumor distribution at right lobe of liver, cases with tumor caliber of feeding artery (CFA) >1 mm were 26, 26, 5, 51, 6, 43, 46 in patients with pCR, versus 87, 64, 103, 158, 59, 125, 159 in patients with pPR, showing significant differences in the above indicators ( Z=3.35, χ2=4.54, 15.71, 12.89, 6.79, P<0.05). (2) Follow-up. All the 311 patients were followed up for 47.0 to 59.0 months, with a median follow-up time of 44.6 months. There were 11 cases undergoing tumor recurrence and 11 cases undergoing tumor metastasis in the 57 patients with pCR, and there were 96 cases undergoing tumor recurrence and 66 cases under-going tumor metastasis in the 254 patients with pPR. The 1-, 3-, 5-year tumor recurrence free rates were 98.2%, 91.1%, 80.3% in the 311 patients, respectively. The 1-, 3-, 5-year tumor recurrence free rates were 100.0%, 91.1%, 80.3% in the 57 patients with pCR, versus 82.0%, 68.4%, 59.4% in the 254 patients with pPR, showing significant differences in the above indicators ( χ2=13.47, P<0.05). Cases with graft loss were 11 and 96 in the 57 patients with pCR and the 254 patients with pPR, respectively, showing a significant difference ( χ2=7.06, P<0.05). (3) Influen-cing factors for prognosis of hepatocellular carci-noma patients after liver transplantation. Results of univariate analysis showed that gender, basic diseases as viral hepatitis C, AFP (20?400 μg/L, >400 μg/L), Milan criteria, microvascular invasion, tumor number, tumor distribution, tumor CFA, times of TACE, effects of TACE were related factors influencing prognosis of hepatocellular carcinoma patients after liver transplantation ( hazard ratio=0.49, 3.97, 1.78, 1.84, 2.41, 1.96, 3.00, 1.76, 0.19, 2.01, 3.07, 95% confidence interval as 0.30?0.81, 2.23?7.05, 1.03?3.06, 1.18?2.85, 1.63?3.56, 1.28?3.01, 2.04?4.40, 1.20?2.59, 0.13?0.28, 1.28?3.14, 1.63?5.76, P<0.05). Results of multi-variate analysis showed that AFP >400 μg/L, exceeding Milan criteria, tumor number as multiple nodule,effects of TACE as pPR were independent risk factors influencing prognosis of hepatocellular carcinoma patients after liver transplantation ( hazard ratio=1.59, 2.06, 1.99, 2.05, 95% confidence interval as 1.22?2.07, 1.35?3.13, 1.29?3.07, 1.02?4.10, P<0.05) and tumor CFA >1 mm was an independent protective factor influencing prognosis of hepatocellular carcinoma patients after liver transplantation ( hazard ratio=0.10, 95% confidence interval as 0.05?0.19, P<0.05). Conclusions:The effects of TACE are related to AFP, microvascular invasion, tumor number, tumor distribution and tumor CFA. AFP >400 μg/L, exceeding Milan criteria, tumor number as multiple nodule,effects of TACE as pPR are independent risk factors influencing prognosis of hepatocellular carcinoma patients after liver transplantation and tumor CFA >1 mm is an independent protective factor influencing prognosis of hepatocellular carcinoma patients after liver transplantation.

Bone regeneration remains a great clinical challenge. Low intensity near-infrared (NIR) light showed strong potential to promote tissue regeneration, offering a promising strategy for bone defect regeneration. However, the effect and underlying mechanism of NIR on bone regeneration remain unclear. We demonstrated that bone regeneration in the rat skull defect model was significantly accelerated with low-intensity NIR stimulation. In vitro studies showed that NIR stimulation could promote the osteoblast differentiation in bone mesenchymal stem cells (BMSCs) and MC3T3-E1 cells, which was associated with increased ubiquitination of the core circadian clock protein Cryptochrome 1 (CRY1) in the nucleus. We found that the reduction of CRY1 induced by NIR light activated the bone morphogenetic protein (BMP) signaling pathways, promoting SMAD1/5/9 phosphorylation and increasing the expression levels of Runx2 and Osterix. NIR light treatment may act through sodium voltage-gated channel Scn4a, which may be a potential responder of NIR light to accelerate bone regeneration. Together, these findings suggest that low-intensity NIR light may promote in situ bone regeneration in a CRY1-dependent manner, providing a novel, efficient and non-invasive strategy to promote bone regeneration for clinical bone defects.
Animals ; Rats ; Bone Morphogenetic Protein 2/metabolism* ; Bone Regeneration ; Cell Differentiation ; Circadian Clocks ; Cryptochromes/metabolism* ; Osteoblasts/metabolism* ; Osteogenesis ; Transcription Factors/metabolism*

Objective To investigate the improvement of symptoms of the patients after treatment in patients with Rome Ⅳ or non-Rome Ⅳ irritable bowel syndrome (IBS),and to explore the influence of IBS diagnosed by different criteria on the patients.Methods From June 2nd to 8th in 2016,at Outpatients Department of Gastroenterology,Union Hospital Affiliated to Tongji Medical College,Huazhong Uiversity of Science and Technology in Wuhan,1 500 outpatients aged over 18 years old and with intestinal symptom were selected for questionnaire.After treatment for six months,IBS patients,non-IBS patients,patients with Rome Ⅳ IBS and patients with non-Rome Ⅳ IBS were followed up by phone calls.After treatment,the improvement of symptoms of the patients was evaluated by irritable bowel syndrome symptom severity scale (IBS-SSS).The degree of influence of IBS diagnosed with different criteria on patients was evaluated by the patient's daily work whether to choose colonoscopy examination,whether to choose medication,and the efficacy of medicine.Student's t test,Mann-Whitney U test and chi-square test were performed for statistical analysis.Results A total of 352 patients with intestinal symptoms were followed-up,including 175 patients with IBS (84 patients with Rome Ⅳ IBS and 91 patients with non-Rome Ⅳ IBS) and 177 non-IBS patients,and 142 patients responded.There were no statistically significant differences in response rate between non-IBS patients and IBS patients (37.3％,66/177 vs.43.4％,76/175),and between patients with Rome Ⅳ IBS and patients with non-Rome Ⅳ IBS (40.5％,34/84 vs.46.2％,42/91) (x2 =1.379 and 0.573,P =0.240 and 0.449).Compared with the non-IBS patients,the degree of satisfaction of medicine was lower in IBS patients (71.4％,30/42 vs.47.5％,19/40).Compared with non-Rome Ⅳ IBS patients,Rome type Ⅳ IBS patients were more likely to receive colonoscopy (35.7％,15/42 vs.58.8％,20/34),and the differences were statistically significant (x2 =4.878 and 4.039,P =0.027 and 0.044).After six months of treatment,symptoms improved in both Rome Ⅳ IBS patients and non-Rome Ⅳ IBS patients (both P ＜ 0.05),however,the symptoms improved more significantly in Rome Ⅳ IBS patients and the total score of IBS-SSS was lower than that of non-Rome Ⅳ IBS patients (-130,-185 to 60 vs.-70,-100 to 28),and the difference was statistically significant (Z =-3.065,P =0.002).The difference was mainly showed the symptom of abdominal pain,and the IBS-SSS abdominal pain score of Rome Ⅳ IBS patients was lower than that of non-Rome Ⅳ IBS patients (-80,-100 to-40 vs.0,-40 to 0),and the difference was statistically significant (Z =-4.631,P ＜ 0.01).Conclusions IBS symptoms influence a lot on the satisfaction degree of treatment in outpatients.Even with similar good therapeutic effects,the Rome Ⅳ IBS symptoms have a more severe impact on patients than non-Rome Ⅳ IBS symptoms.

To analyze and research the number and size of public hospitals of our country at the present stage, and explore the regional health planning of public hospitals under the background of China's new medical reform, provide the scientific basis for our further layout of regional health planning for public hospitals of our country. Methods Mainly use the method of the document analysis, by collecting and analyzing the literature related to the regional health planning of public hospitals under the new health reform. And relevant data on China Health Statistics Yearbook 2011 were analyzed. Results The irrational regional health planning and layout design of public hospitals not only seriously affect the efficiency of health care resources, but also exacerbate the difficulty and high cost of people getting medical service. Conclusion Under the new health care reform, the definition of public hospitals and the positioning and functionality of public hospitals need to be re-examined. The following three aspects will solve the problem of regional health planning of public hospitals. First, to moderately reduce the number and size of public hospitals; second, to determine and adjust the number of public hospitals at all levels; Third, to reasonably lay out urban and rural public hospital.

Breast Neoplasms ; diagnosis ; Female ; Humans ; Image Processing, Computer-Assisted ; Immunohistochemistry ; Spectrum Analysis

BACKGROUND:Pain is the extremely common disease in clinic. At present, acupuncture provides good therapeutic effect on it. But, there are many methods in acupuncture with various advantages individually.To understand the differences in therapeutic effects on pain with various needling techniques is significant in clinic. In 1999, the relevant observation was carried on in the demand of Ecuadorian Medical Pain Association.OBJECTIVE: To observe the differences in therapeutic effects on pain with various needling techniques.DESIGN: Randomized controlled observation was designed.SETTING: Department of Pain, Hospital General de las FF. AA. Quito, Ecuador, Department of Traditional Chinese Medicine and 1st Department of Surgery, General Hospital of Chengdu MilitaryArea Command of Chinese PLA.PARTICIPANTS: Totally 360 cases of lumber strain and hyperplastic spondylitis were selected in Department of Pain, Clinic of Ecuadorian 3rd Military General Hospital from May 1999 to November 2000, in which,179 cases were lumber strain and 181 cases were hyperplastic spondylitis.The groups were randomized in two kinds of diseases, named for lumber strain, dermal-needling group (88 cases) and body-acupuncture group (91cases); for hyperplastic spondylitis, dermal-needling group (92 cases) and body-acupuncture group (89 cases).METHODS: Dermal needling and body acupuncture were used to treat the diseases respectively and the symptom changes were observed before and after treatment simultaneously. The treatment was given once every two days. 5 treatments made one basic course for lumber strain and 7 treatments for hyperplastic spondylitis. The treating results were evaluated according to Budzynski grading criteria on pain. MEPS statistical software was used for statistical management of data.MAIN OUTCOME MEASURES: Pain relieving before and after treatment with dermal needling and body acupuncture for lumber strain and hyperplastic spondylitis was evaluated. Correlative analysis on therapeutic effects and course of treatment for different diseases with same therapy and on same disease with different therapies were carried on.RFSULTS: Altogether 366 cases were observed and 6 of them were excluded. Totally, 360 cases finished the experiment. ① The severity was alleviated in pain grading after treatment with dermal needling and body acupuncture compared with that before the treatment (P ＜ 0.01). ② In treatment of lumber strain and hyperplastic spondylitis with dermal needling, the therapeutic effects on lumber strain were more remarkable (P ＜ 0.01). The therapeutic effects of dermal needling on lumber strain were superior to that of body acupuncture (P ＞ 0.05). ③ The therapeutic effects of body acupuncture group on pain of Ⅰ grade in hyperplastic spondylitis were remarkably better than that of dermal needling group,but the significant difference in the total therapeutic effects of two techniques did not present (P ＞ 0.05). ④ When pain grading was reduced by 1 level in two groups, the average times of treatment in dermal needling group were less than that in body-acupuncture group (P ＜ 0.05).CONCLUSION: Good therapeutic effects of dermal needling and body acupuncture are achieved for both hyperplastic spondylitis and lumber strain,in which, the therapeutic effects of dermal needling are remarkable on injury of soft tissue and achieved swiftly; body acupuncture improves pain in hyperplastic spondylitis more radically compared with dermal needling.