Objective:To analyze the fail mode of neoadjuvant therapy combined with surgery for locally advanced esophageal squamous cell carcinoma (ESCC) after long-term follow-up.Methods:Clinical data of consecutive 238 patients with locally advanced resectable ESCC who underwent neoadjuvant therapy combined with surgery in Zhejiang Cancer Hospital from September 2012 to October 2019 were retrospectively analyzed. The failure mode in the whole cohort was analyzed after long-term follow-up. The overall survival (OS) and disease free survival (DFS) rates were analyzed by Kaplan-Meier method. Survival differences were determined by log-rank test.Results:The pathological complete response (pCR) rate was 42.0% in 238 patients. After a median follow-up of 46.1 months, tumor progression occurred in 96 patients (40.3%), including 25 patients (10.5%) with local recurrence, 61 patients (25.6%) with distant metastases, and 10 patients (4.2%) with simultaneous local recurrence and distant metastases. The median OS and DFS were 64.7 months and 49.9 months. And the 3-, 5-, and 7-year OS and DFS rates were 70.0%, 52.8%, 36.4% and 63.5%, 42.5%, and 30.0%, respectively. The 3-, 5-, and 7-year locoregional recurrence-free survival rates and distant metastasis-free survival rates were 86.0%, 71.4%, 61.2% and 70.6%, 55.9%, 43.0%. Compared with non-pCR patients, the overall progression rate and distant metastasis rate of pCR patients were lower (26.0% vs. 50.7%, 16.0% vs. 32.6%, both P<0.05). And the 3-, 5-, and 7-year OS (83.0% vs. 60.2%, 69.7% vs. 41.7%, 50.4% vs. 27.7%, all P<0.001) and DFS rates (80.4% vs. 51.4%, 63.9% vs. 31.2%, 45.9% vs. 20.3%, all P<0.001) were significantly better in pCR patients. Conclusions:Distant metastasis is the main failure mode of patients with locally advanced ESCC after neoadjuvant therapy. Patients with postoperative pCR can achieve better long-term survival.

OBJECTIVE: To automatically construct lips symmetry reference plane (SRP) based on posed smile, and to evaluate its advantages over conventional digital aesthetic design. METHODS: Eighteen subjects' three-dimensional facial and dentition data were gathered in this study. The lips SRP of experimental groups were used with the standard weighted Procrustes analysis (WPA) algorithm and iterative closest point (ICP), respectively. A reference plane defined by experts based on regional ICP algorithm, served as the truth plane. The angle error values between the lips SRP of WPA algorithm in the experimental groups and the truth plane were evaluated in this study, and the lips SRP of ICP algorithm of the experimental groups was calculated in the same way. The lips SRP based on posed smile as a reference for aesthetic design and evaluate preliminary clinical application. RESULTS: The average angle error between the lips SRP of WPA algorithm and the truth plane was 1.78°±1.24°, which was smaller than that between the lips SRP of ICP and the truth plane 7.41°±4.31°. There were significant differences in the angle errors among the groups (P < 0.05). In the aesthetic design of anterior teeth, automatically constructing the lips SRP of WPA algorithm based on posed smile and the original symmetry plane by re-ference compared with the prosthetic design, the subjects' scores on the lips SRP of WPA algorithm based on posed smile (8.48±0.57) were higher than those on the original symmetry plane (5.20±1.31). CONCLUSION Automatically constructing the lips SRP of WPA algorithm based on posed smile was more accurate than ICP algorithm, which was consistent with the truth plane. Moreover, it can provide an important reference for oral aesthetic diagnosis and aesthetic analysis of the restoration effect. In the aesthetic design of anterior teeth, automatically constructing the lips SRP of WPA algorithm based on posed smile can improve the patients' satisfaction in esthetic rehabilitation.
Esthetics, Dental ; Humans ; Lip ; Smiling ; Tooth ; Workflow

BACKGROUND: Bendamustine was approved in China on May 26th, 2019 by the National Medical Product Administration for the treatment of indolent B-cell non-Hodgkin lymphoma (NHL). The current study was the registration trial and the first reported evaluation of the efficacy, safety, and pharmacokinetics of bendamustine in Chinese adult patients with indolent B-cell NHL following relapse after chemotherapy and rituximab treatment. METHODS: This was a prospective, multicenter, open-label, single-arm, phase 3 study (NCT01596621; C18083/3076) with a 2-year follow-up period. Eligible patients received bendamustine hydrochloride 120 mg/m2 infused intravenously on days 1 and 2 of each 21-day treatment cycle for at least six planned cycles (and up to eight cycles). The primary endpoint was the overall response rate (ORR); and secondary endpoints were duration of response (DoR), progression-free survival (PFS), safety, and pharmacokinetics. Patients were classified according to their best overall response after initiation of therapy. Proportions of patients in each response category (complete response [CR], partial response [PR], stable disease, or progressive disease) were summarized along with a two-sided binomial exact 95% confidence intervals (CIs) for the ORR. RESULTS: A total of 102 patients were enrolled from 20 centers between August 6th, 2012, and June 18th, 2015. At the time of the primary analysis, the ORR was 73% (95% CI: 63%-81%) per Independent Review Committee (IRC) including 19% CR and 54% PR. With the follow-up period, the median DoR was 16.2 months by IRC and 13.4 months by investigator assessment; the median PFS was 18.6 months and 15.3 months, respectively. The most common non-hematologic adverse events (AEs) were gastrointestinal toxicity, pyrexia, and rash. Grade 3/4 neutropenia was reported in 76% of patients. Serious AEs were reported in 29 patients and five patients died during the study. Pharmacokinetic analysis indicated that the characteristics of bendamustine and its metabolites M3 and M4 were generally consistent with those reported for other ethnicities. CONCLUSION: Bendamustine is an active and effective therapy in Chinese patients with relapsed, indolent B-cell NHL, with a comparable risk/benefit relationship to that reported in North American patients. CLINICAL TRIAL REGISTRATION ClinicalTrials.gov, No. NCT01596621; https://clinicaltrials.gov/ct2/show/NCT01596621.
Adult ; Antineoplastic Combined Chemotherapy Protocols ; Bendamustine Hydrochloride/therapeutic use* ; China ; Humans ; Lymphoma, Non-Hodgkin/drug therapy* ; Neoplasm Recurrence, Local/drug therapy* ; Prospective Studies ; Rituximab/therapeutic use*

Objective To explore the theories, content and approaches of integrating physical activity in children's eye health service system in the context of health services. Methods From the perspectives of six building blocks of WHO health system, namely, leadership and governance, financing, human resources for health, service delivery, medical technology, and health information system, we analyzed the policy framework and key contents related to school-based eye health and physical activity, and explored how to promote the implementation of physical activity into the school-based eye health service system, and the integration of physical activity into the eye health continuum: prevention, intervention, rehabilitation, and health promotion. Results In perspective of health system, the integration of physical activity into school-based eye health services should be in accordance with the five principles of cross-cutting health services, namely, universal accessibility and equity, human rights, evidence-based, life-span, and empowerment. According to the World Vision Report, WHO advocates to build a person-centered eye health service system, and person-centeredness is the core concept of the new model of school-based eye health services and physical activity integration. WHO advocates a school-based approach to education and physical activity in health-promoting schools to promote student health, physical activity as a preventive, interventional, rehabilitation and health promotive measure related to children's eye health, and vigorously train professionals within schools who have knowledge and skills related to physical activity and eye health, build an information system on physical activity and children's eye health, and promote the integration of physical activity into the school-based eye health service system. Conclusion Physical activity is an important measure to promote children's eye health and an important component to achieve a person-centered eye health service system. Based on the six building blocks of the WHO health service system, a school-based eye health service that integrates a theoretical and methodological system of physical activity is constructed, requiring the provision of health promotion methods such as education and physical activity in the school setting, to enhance leadership and governance of eye health services based on educational and physical activity approaches in the school setting, establish new funding mechanisms, provide financial security, develop human resources related to physical activity for eye health, improve related service delivery systems, develop high-quality physical activity intervention eye health techniques and equipment, and integrate information on children's physical activity and eye health into school health information systems to achieve children's eye health and promote their physical and mental development.

Lysophosphatidic acid(LPA)is a small bioactive phospholipid that mediates various cellular processes such as proliferation, survival, and migration. In particular, LPA signaling has been shown to affect the development of diverse tissues. Our previous work demonstrated that LPA could promote primary neonatal rat cardiomyocytes proliferation. However, the role of LPA and its receptor in postnatal heart de-velopment is unknown. By using databases for biological information and RT-qPCR, we analyzed the ex-pression of six LPA receptors (LPA

The current epidemic situation of corona virus disease-19 (COVID-19) still remained severe. As the National Clinical Research Center for Infectious Diseases, the First Affiliated Hospital of Zhejiang University School of Medicine is the primary medical care center for COVID-19 inZhejiang Province. Based on the present expert consensus carried out by National Health Commission and National Administration of Traditional Chinese Medicine, our team summarized and established an effective treatment strategy centered on "Four-Anti and Two-Balance" for clinical practice. The "Four-Anti and Two-Balance"strategy included antivirus, anti-shock, anti-hyoxemia, anti-secondary infection, and maintaining of water, electrolyte and acid base balance and microecological balance. Meanwhile, integrated multidisciplinarypersonalized treatment was recommended to improve therapeutic effect. The importance of early viralogical detection, dynamic monitoring of inflammatory indexes and chest radiograph was emphasized in clinical decision-making. Sputum was observed with the highest positive rate of RT-PCR results. Viral nucleic acids could be detected in10% patients'blood samples at acute periodand 50% of patients had positive RT-PCR results in their feces. We also isolated alive viral strains from feces, indicating potential infectiousness of feces.Dynamic cytokine detection was necessary to timely identifyingcytokine storms and application of artificial liver blood purification system. The "Four-Anti and Two-Balance"strategyeffectively increased cure rate and reduced mortality. Early antiviral treatment could alleviate disease severity and prevent illness progression, and we found lopinavir/ritonavir combined with abidol showed antiviraleffects in COVID-19. Shock and hypoxemia were usually caused by cytokine storms. The artificial liver blood purification system could rapidly remove inflammatory mediators and block cytokine storm.Moreover, it also favoredthe balance of fluid, electrolyte and acid-base and thus improved treatment efficacy in critical illness. For cases of severe illness, early and also short periods of moderate glucocorticoid was supported. Patients with oxygenation index below 200 mmHg should be transferred to intensive medical center. Conservative oxygen therapy was preferred and noninvasive ventilation was not recommended. Patients with mechanical ventilation should be strictly supervised with cluster ventilator-associated pneumonia prevention strategies. Antimicrobial prophylaxis should be prescribed rationally and was not recommended except for patients with long course of disease, repeated fever and elevated procalcitonin (PCT), meanwhile secondary fungal infection should be concerned.Some patients with COVID-19 showed intestinal microbialdysbiosis with decreasedprobiotics such as and . Nutritional and gastrointestinal function should be assessed for all patients.Nutritional support and application of prebiotics or probiotics were suggested to regulate the balance of intestinal microbiota and reduce the risk of secondary infection due to bacterial translocation. Anxiety and fear were common in patients with COVID-19. Therefore, we established dynamic assessment and warning for psychological crisis. We also integrated Chinese medicine in treatment to promote disease rehabilitation through classification methods of traditional Chinese medicine. We optimized nursing process for severe patients to promote their rehabilitation. It remained unclear about viral clearance pattern after the SARS-CoV-2 infection. Therefore, two weeks' quarantine for discharged patients was required and a regular following up was also needed.The Zhejiang experience above and suggestions have been implemented in our center and achieved good results. However, since COVID-19 was a newly emerging disease, more work was warranted to improve strategies of prevention, diagnosis and treatment for COVID-19.

Objective:To explore the effect of closed skills physical activity with additional dynamic visual task on dynamic visual acuity and static visual acuity for pupils with myopia at grade four at primary school. Methods:In September, 2019, 37 pupils with myopia at grade four in Daicheng Experimental Primary School, Suzhou City were selected. In light of mechanism of refractive system, the intervention of closed-skilled physical activity with dynamic visual task was developed. They were intervened for 16 weeks. The dynamic visual acuity and static visual acuity were measured before intervention, and eight and 16 weeks after intervention. Results:Both dynamic visual acuity and static visual acuity improved significantly in all the pupils with myopia after 16 weeks of intervention (F > 15.933, P < 0.001), both pupils with mild and moderate myopia (|t| > 3.353, P < 0.05). The static visual acuity was better in pupils with moderate myopic than with mild myopia (t = -2.830, P < 0.01). Conclusion:Closed skills physical activity with dynamic visual task could improve the visual acuity of puplis with myopia at grade four at primary school.

The current epidemic situation of coronavirus disease 2019 (COVID-19) still remained severe. As the National Clinical Research Center for Infectious Diseases, the First Affiliated Hospital of Zhejiang University School of Medicine is the primary medical care center for COVID-19 in Zhejiang province. Based on the present expert consensus carried out by National Health Commission and National Administration of Traditional Chinese Medicine, our team summarized and established an effective treatment strategy centered on "Four-Anti and Two-Balance" for clinical practice. The "Four-Anti and Two-Balance" strategy included antivirus, anti-shock, anti-hyoxemia, anti-secondary infection, and maintaining of water, electrolyte and acid base balance and microecological balance. Meanwhile, integrated multidisciplinary personalized treatment was recommended to improve therapeutic effect. The importance of early viralogical detection, dynamic monitoring of inflammatory indexes and chest radiograph was emphasized in clinical decision-making. Sputum was observed with the highest positive rate of RT-PCR results. Viral nucleic acids could be detected in 10%patients' blood samples at acute period and 50%of patients had positive RT-PCR results in their feces. We also isolated alive viral strains from feces, indicating potential infectiousness of feces.Dynamic cytokine detection was necessary to timely identifying cytokine storms and application of artificial liver blood purification system. The "Four-Anti and Two-Balance" strategy effectively increased cure rate and reduced mortality. Early antiviral treatment could alleviate disease severity and prevent illness progression, and we found lopinavir/ritonavir combined with abidol showed antiviral effects in COVID-19. Shock and hypoxemia were usually caused by cytokine storms. The artificial liver blood purification system could rapidly remove inflammatory mediators and block cytokine storm.Moreover, it also favored the balance of fluid, electrolyte and acid-base and thus improved treatment efficacy in critical illness. For cases of severe illness, early and also short period of moderate glucocorticoid was supported. Patients with oxygenation index below 200 mmHg should be transferred to intensive medical center. Conservative oxygen therapy was preferred and noninvasive ventilation was not recommended. Patients with mechanical ventilation should be strictly supervised with cluster ventilator-associated pneumonia prevention strategies. Antimicrobial prophylaxis was not recommended except for patients with long course of disease, repeated fever and elevated procalcitonin (PCT), meanwhile secondary fungal infection should be concerned.Some patients with COVID-19 showed intestinal microbial dysbiosis with decreased probiotics such as and , so nutritional and gastrointestinal function should be assessed for all patients.Nutritional support and application of prebiotics or probiotics were suggested to regulate the balance of intestinal microbiota and reduce the risk of secondary infection due to bacterial translocation. Anxiety and fear were common in patients with COVID-19. Therefore,we established dynamic assessment and warning for psychological crisis. We also integrated Chinese medicine in treatment to promote disease rehabilitation through classification methods of traditional Chinese medicine. We optimized nursing process for severe patients to promote their rehabilitation. It remained unclear about viral clearance pattern after the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Therefore, two weeks' quarantine for discharged patients was required and a regular following up was also needed.The Zhejiang experience and suggestions have been implemented in our center and achieved good results. However, since COVID-19 was a newly emerging disease, more work was warranted to improve strategies of prevention, diagnosis and treatment for COVID-19.
Betacoronavirus ; isolation & purification ; China ; epidemiology ; Coronavirus Infections ; diagnosis ; epidemiology ; therapy ; virology ; Disease Management ; Early Diagnosis ; Feces ; virology ; Humans ; Pandemics ; Pneumonia, Viral ; diagnosis ; epidemiology ; therapy ; virology ; Sputum ; virology

Methyl-CpG binding protein 2 (MeCP2) is a basic nuclear protein involved in the regulation of gene expression and microRNA processing. Duplication of MECP2-containing genomic segments causes MECP2 duplication syndrome, a severe neurodevelopmental disorder characterized by intellectual disability, motor dysfunction, heightened anxiety, epilepsy, autistic phenotypes, and early death. Reversal of the abnormal phenotypes in adult mice with MECP2 duplication (MECP2-TG) by normalizing the MeCP2 levels across the whole brain has been demonstrated. However, whether different brain areas or neural circuits contribute to different aspects of the behavioral deficits is still unknown. Here, we found that MECP2-TG mice showed a significant social recognition deficit, and were prone to display aversive-like behaviors, including heightened anxiety-like behaviors and a fear generalization phenotype. In addition, reduced locomotor activity was observed in MECP2-TG mice. However, appetitive behaviors and learning and memory were comparable in MECP2-TG and wild-type mice. Functional magnetic resonance imaging illustrated that the differences between MECP2-TG and wild-type mice were mainly concentrated in brain areas regulating emotion and social behaviors. We used the CRISPR-Cas9 method to restore normal MeCP2 levels in the medial prefrontal cortex (mPFC) and bed nuclei of the stria terminalis (BST) of adult MECP2-TG mice, and found that normalization of MeCP2 levels in the mPFC but not in the BST reversed the social recognition deficit. These data indicate that the mPFC is responsible for the social recognition deficit in the transgenic mice, and provide new insight into potential therapies for MECP2 duplication syndrome.

Objective::To finding the main research contents, research frontier, author and institutional cooperation of traditional Chinese medicine(TCM) for treating henoch-schonlein purpura(HSP). Providing reference for the research and development of TCM for treating the disease. Method::Using Citespace to analyze 2 878 TCM articles related to HSP retrieved from CNKI, cluster analysis and burst analysis of literature keywords, co-occurring authors and institutional cooperation analysis. Result::Since 1995, the number of related literature was growing rapidly and had been stable at more than 100 per year after 2005.Cluster analysis showed 32 clusters, consisting of 396 nodes and 638 lines. The main clustering results include Children with allergic purpura, blood-activating and stasis-resolving drug, Henoch-Schonlein purpura nephritis, blood-cooling drugs, clinical observation, etc. Break analysis yielded 52 emergent words. It can be seen that TCM treatment of HSP is mainly based on cooling blood, followed by activating blood to eliminate stagnation and clearing heat. Commonly used drugs are Moutan Cortex, Paeoniae Radix Rubra, and Rehmanniae Radix, etc. Clinically, it pays more attention to the experience of famous doctors, research on Children with allergic purpura, etc.The author's cooperation network has obtained the maps of the three main cooperation teams with DING Ying, SUN Yi-qiu and HE Ping as the core. The Density of institutional cooperation network is 0.007 1. Conclusion::The main research contents of TCM for treating HSP include Children with allergic purpura, blood-activating and stasis-resolving drug, HSP nephritis, blood-cooling drugs, clinical observation, etc. Children with allergic purpura, experience from famous doctor, HSP nephritis and clinical efficacy is the foremost current research hotspot. A number of research teams have been formed that are relatively stable, but the institutional cooperation is scattered.