OBJECTIVE To analyze the research status， hotspots and trends in the research of intravenous thrombolytic drugs in the treatment of acute ischemic stroke. METHODS The original studies related to intravenous thrombolytic drugs for acute ischemic stroke were collected by searching the Web of Science core database； the authors， countries/regions， institutions and keywords of the literature were visualized and analyzed using CiteSpace 6.1.R6 software. RESULTS A total of 1 810 articles were included， and the number of articles published showed an increasing trend year by year， with the United States （556 articles） having the largest number of articles， and China ranking the second （339 articles， with centrality of 0）. The most published author was Ahmed of Sweden （32 articles）， and the most published institution was the University of Calgary in Canada （80 articles）. The current research status and hotspots were mainly the application and therapeutic exploration of new thrombolytic drugs， and the frontier and development trend were the adverse prognosis of neurological deterioration and hemorrhagic transformation accompanied by intravenous thrombolytic drug treatment. CONCLUSIONS The research hotspots and frontier about intravenous thrombolytic drugs for acute ischemic stroke are mainly the third generation of intravenous tissue plasminogen activator， and the exploration of new intravenous thrombolytic drugs and their safety and effectiveness will be the future research hotspots. Chinese scholars and research teams should strengthen cooperation and exchanges with other countries， which can be strengthened by carrying out multi-center clinical trials.

Gastric cancer(GC)is one of the most common and high mortality tumors in the world,and the clinical staging during diagnosis is closely related to the prognosis of patients.Therefore,finding sensitive diagnostic biomarkers to improve the early diagnosis rate has become an urgent issue.Exosomes are nanoscale extracellular vesicles secreted by various cells,which play an important role in cellular communication by transporting bioactive substances in tumor microenvironment(TME).CircRNA is a type of non-coding RNA with a specific structure.Because it is difficulty in degradation,it can be enriched in extracellular vesicles and participate in various pathophysiological processes mediated by it.Exo-circRNA can affect the proliferation,invasion,drug resistance and tissue metastasis of tumor cells,and has more significant diagnostic specificity than conventional diagnostic biomarkers in clinical practice.It may become a supplement to biomarker for the diagnosis and prognosis of GC.This article briefly introduces the characteristics,formation mechanism and role of extracellular vesicles and circRNA in GC.It discusses in detail the role of exo-circRNA in the occurrence and development of GC,and discusses their potential clinical application value and challenges in GC.

Kashin-Beck disease (KBD) is an endemic and degenerative osteoarthropathy that can cause damage to the endochondral ossification of the limbs during development. The etiology is still unclear. In recent years, scholars at home and abroad have studied the mechanism of T-2 toxin and its metabolites causing KBD cartilage damage from the perspectives of immunotoxicity, oxidative stress, inflammatory response, cell apoptosis, etc., mainly including transforming growth factor-β receptor (TGF-βRs) signaling pathway, immune regulatory factor, inflammatory factor IL-1β and apoptosis enzyme activating factor 1 (APAF1), which promote the progression of KBD by inducing human chondrocyte injury, inhibiting matrix synthesis and accelerating cellular catabolism. This article reviews the research progress on the immunotoxicity of T-2 toxin and its toxic effects on KBD cartilage injury at the molecular level, in order to provide a scientific basis for prevention and treatment of KBD.

Objective:To analyze the impact of global budget on the medical flow treatment and fund allocation in a non-compact medical community based on the symbiosis theory, so as to provide references for relevant authorities to formulate policies for the medical community.Methods:Data on outpatient and emergency visits, discharges, and medical insurance fund usage of the leading hospital and primary medical and health institutions in a non-compact medical community were collected from the health information system of a certain city. The time range of the data spanned from January 2017 to December 2019. The total budget was implemented in April 2018. The symbiotic system of the non-compact medical community was analyzed based on the theory of symbiosis. Descriptive analysis and intermittent time series segmented regression model were used to analyze the changes in indexes related to the flow of medical treatment and fund allocation between the leading hospital and primary institutions under the global budget.Results:The non-compact medical community′s symbiotic system had developed a continuous symbiotic model in organization and an asymmetric reciprocal symbiotic model in behavior. From the perspective of medical treatment flow, the number of outpatient and emergency visits of leading hospital and primary institutions in the medical community showed an upward trend, with little change in the number of discharged patients from 2017 to 2019; The number of patients transferred by the leading hospital increased from 32 in 2017 to 87 in 2019. According to the analysis of the intermittent time series segmented regression model, after the implementation of global budget, the proportion of outpatient and emergency visits in leading hospital was decreased ( β3=-0.43, P<0.05), the proportion of outpatient and emergency visits in primary institutions was on the rise ( β3= 0.02, P<0.05). In terms of fund allocation, the share of health insurance fund of the leading hospital increased from 45.98% in 2017 to 46.51% in 2019, and the primary medical and health institutions decreased from 23.44% to 18.06%, as well as the ratio of per capita income of primary medical and health institutions to that of leading hospitals was decreased from 72.62% to 60.79%. Conclusions:Under the global budget, the outpatient and emergency medical treatment flow in a non-compact medical community had been optimized. However, there was an uneven distribution of funds among medical institutions at all levels. Thus it was recommended to continue to give full play to the positive incentive effect of the global budget, establish a scientific mechanism for distributing benefits, and strengthen supervision and management.

Objective:To explore the effect of three-dimensional(3D) design and printing in the reoperation of asymmetric deformity after orthognathic surgery.Methods:Patients of facial asymmetry after orthognathic surgery were included in the Department of Stomatology, Shenzhen University General Hospital and Department of Oral & Maxillofacial Surgery, Shenzhen Stomatology Hospital Affiliated to Shenzhen University from January 2016 to August 2020. Surgical plans and guide plates (positioning guide plate, bone cutting guide plate, reset guide plate) were made by 3D design and printing. During the operations, guide plates were used to guide osteotomy. The facial shape satisfaction of clinicians/patients/third-party were recorded and analyzed at preoperation and 6-12 months postoperation. These patients’ CT scan data was imported to the digital surgery software. Then the distance of chin-midpoint to mid-sagittal plane and the difference of bilateral protuberant point of mandible body to mid-sagittal plane were measured at preoperation and 6-12 months postoperation to determine whether the asymmetry were corrected and postoperative distance were the same as the preoperative design. Data analysis was conducted using SPSS 17.0 statistical software, and measurement data were expressed as Mean±SD. The preoperative and postoperative satisfaction of patients/clinicians/third-party, digital data of preoperation/postoperation and digital data of design-operations/postoperation were analyzed by paired t-test. Analysis of variance and dunnett- t test were used to compare the satisfaction of the surgeon, the third party and patients before and after operation. Results:There were 16 cases of facial asymmetry after orthognathic surgery, including 3 males and 13 females, aged from 18 to 35 years. In 9 cases, genioplasty were used to correct chin deviation. In the other 4 cases, unilateral buccal cortical bone resection were used to correct mandibular body deviation. In the last 3 cases, genioplasty and unilateral buccal cortical bone resection were both applied. All 16 patients successfully received the operation according to the preoperative digital designed plate. Postoperative follow-up ranged 6 months to 1 year. In the 12 cases of genioplasty, the distance of chin-midpoint to mid-sagittal plane reduced from(4.99±0.83) mm preoperatively to (1.63±0.80) mm postoperatively and the difference significant ( t=9.09, P<0.001). There was no significant difference between the distance of preoperative design [(1.50±0.43) mm] and the postoperative one ( t=-0.83, P=0.423). In the 7 cases of unilateral buccal cortical bone resection, the difference of bilateral protuberant point of mandible body to mid-sagitta plane reduced from (7.26±1.20) mm preoperatively to (2.44±0.56) mm postoperatively and the difference was statistically significant ( t=10.26, P<0.001). There was no significant difference was observed between the distance of preoperative design [(2.39±0.16) mm] and the postoperative one ( t=-0.29, P=0.779). The preoperative satisfaction of patients, clinicians and third-party were 65.94±8.21, 79.69±5.91, 79.38±7.50. The postoperative satisfaction of patients, clinicians and third-party were 90.00±5.48, 90.63±2.50, 90.00±4.08. The postoperative satisfaction of patients, chief surgeon and third party was higher than that preoperative satisfaction and the difference was statistically significant( t=-9.15, P<0.001; t=-7.50, P<0.001; t=-6.04, P<0.001). The difference of preoperation satisfaction was statistically significant( F=18.66, P<0.001). The difference of satisfaction of the clinicians and the patients was statistically significant ( P<0.001). The difference of satisfaction of the third-party and the patients was statistically significant ( P<0.001). The difference of postoperation satisfaction was not statistically significant( F=0.12, P=0.889). Conclusions:3D design and printing can 3D analyze comprehensively, simulate surgery accurately, visualize proposed result and guide 3D printing digital guiding plate to perform surgery accurately. In addition, it can improve postoperative satisfaction. So 3D design and printing had obvious advantages in the secondary surgery of asymmetric deformity correction after orthognathic surgery.

Objective:To explore the effect of three-dimensional(3D) design and printing in the reoperation of asymmetric deformity after orthognathic surgery.Methods:Patients of facial asymmetry after orthognathic surgery were included in the Department of Stomatology, Shenzhen University General Hospital and Department of Oral & Maxillofacial Surgery, Shenzhen Stomatology Hospital Affiliated to Shenzhen University from January 2016 to August 2020. Surgical plans and guide plates (positioning guide plate, bone cutting guide plate, reset guide plate) were made by 3D design and printing. During the operations, guide plates were used to guide osteotomy. The facial shape satisfaction of clinicians/patients/third-party were recorded and analyzed at preoperation and 6-12 months postoperation. These patients’ CT scan data was imported to the digital surgery software. Then the distance of chin-midpoint to mid-sagittal plane and the difference of bilateral protuberant point of mandible body to mid-sagittal plane were measured at preoperation and 6-12 months postoperation to determine whether the asymmetry were corrected and postoperative distance were the same as the preoperative design. Data analysis was conducted using SPSS 17.0 statistical software, and measurement data were expressed as Mean±SD. The preoperative and postoperative satisfaction of patients/clinicians/third-party, digital data of preoperation/postoperation and digital data of design-operations/postoperation were analyzed by paired t-test. Analysis of variance and dunnett- t test were used to compare the satisfaction of the surgeon, the third party and patients before and after operation. Results:There were 16 cases of facial asymmetry after orthognathic surgery, including 3 males and 13 females, aged from 18 to 35 years. In 9 cases, genioplasty were used to correct chin deviation. In the other 4 cases, unilateral buccal cortical bone resection were used to correct mandibular body deviation. In the last 3 cases, genioplasty and unilateral buccal cortical bone resection were both applied. All 16 patients successfully received the operation according to the preoperative digital designed plate. Postoperative follow-up ranged 6 months to 1 year. In the 12 cases of genioplasty, the distance of chin-midpoint to mid-sagittal plane reduced from(4.99±0.83) mm preoperatively to (1.63±0.80) mm postoperatively and the difference significant ( t=9.09, P<0.001). There was no significant difference between the distance of preoperative design [(1.50±0.43) mm] and the postoperative one ( t=-0.83, P=0.423). In the 7 cases of unilateral buccal cortical bone resection, the difference of bilateral protuberant point of mandible body to mid-sagitta plane reduced from (7.26±1.20) mm preoperatively to (2.44±0.56) mm postoperatively and the difference was statistically significant ( t=10.26, P<0.001). There was no significant difference was observed between the distance of preoperative design [(2.39±0.16) mm] and the postoperative one ( t=-0.29, P=0.779). The preoperative satisfaction of patients, clinicians and third-party were 65.94±8.21, 79.69±5.91, 79.38±7.50. The postoperative satisfaction of patients, clinicians and third-party were 90.00±5.48, 90.63±2.50, 90.00±4.08. The postoperative satisfaction of patients, chief surgeon and third party was higher than that preoperative satisfaction and the difference was statistically significant( t=-9.15, P<0.001; t=-7.50, P<0.001; t=-6.04, P<0.001). The difference of preoperation satisfaction was statistically significant( F=18.66, P<0.001). The difference of satisfaction of the clinicians and the patients was statistically significant ( P<0.001). The difference of satisfaction of the third-party and the patients was statistically significant ( P<0.001). The difference of postoperation satisfaction was not statistically significant( F=0.12, P=0.889). Conclusions:3D design and printing can 3D analyze comprehensively, simulate surgery accurately, visualize proposed result and guide 3D printing digital guiding plate to perform surgery accurately. In addition, it can improve postoperative satisfaction. So 3D design and printing had obvious advantages in the secondary surgery of asymmetric deformity correction after orthognathic surgery.

Objective:To report 3 cases of rare subtypes of hereditary epidermolysis bullosa.Methods:Clinical data were collected from the probands and their relatives, whole-exome sequencing was performed to screen disease-causing mutations in the probands, and Sanger sequencing or qPCR was conducted to verify the mutations in patients and their relatives.Results:Case 1 mainly presented with linear red scars on the back, and the proband, her mother with similar clinical manifestations and her asymptomatic daughter all carried a mutation c.4573G>A (p.Gly1525Arg) in the COL7A1 gene. Case 2 presented with generalized reticular pigmentation all over the body and occasional blisters restricted to the hand and foot, and carried a de novo mutation c.74C>T (p.Pro25Leu) in the KRT5 gene. Case 3 presented with pigmentation abnormalities mainly located at the sun-exposed sites and incomplete syndactyly of the left hand, and carried homozygous deletion mutations in exons 2-6 of the FERMT1 gene, which were inherited from her asymptomatic parents. Case 1 was diagnosed with dominant dystrophic epidermolysis bullosa pruriginosa, case 2 was diagnosed with epidermolysis bullosa simplex with mottled pigmentation, and case 3 was diagnosed with Kindler epidermolysis bullosa. Conclusion:The clinical manifestations of epidermolysis bullosa vary greatly, and gene detection is very important for confirmation of diagnosis of its rare types.

Objective:To explore the willingness and main influencing factors of using mobile health management APP in patients after percutaneous coronary intervention (PCI) based on integrated information technology acceptance and use model.Methods:From July to November 2021, a total of 308 patients after PCI in Department of Cardiovascular Medicine of two ClassⅢ Grade A hospitals in Anhui Province were selected as the research objects by the convenient sampling method. The general information questionnaire and the questionnaire on patients' willingness to use mobile health management APP were used to investigate the patients after PCI. Structural equation model was used to analyze the influencing factors and path relationship of patients' willingness to use after PCI.Results:Contributing factors, effort expectation and social influence had positive effects on patients' willingness to use PCI ( P< 0.05) , and the effect values were 0.554, 0.247 and 0.138, respectively. Perceived risk and effort expectation had effects on performance expectation of patients after PCI ( P<0.05) . Conclusions:Enhancing technical support in various ways, giving play to the publicity role of medical staff, important relatives and friends and new media and improving the ease of use of products can help improve the willingness of patients to use mHealth APP after PCI.

Objective:To explore the willingness and main influencing factors of using mobile health management APP in patients after percutaneous coronary intervention (PCI) based on integrated information technology acceptance and use model.Methods:From July to November 2021, a total of 308 patients after PCI in Department of Cardiovascular Medicine of two ClassⅢ Grade A hospitals in Anhui Province were selected as the research objects by the convenient sampling method. The general information questionnaire and the questionnaire on patients' willingness to use mobile health management APP were used to investigate the patients after PCI. Structural equation model was used to analyze the influencing factors and path relationship of patients' willingness to use after PCI.Results:Contributing factors, effort expectation and social influence had positive effects on patients' willingness to use PCI ( P< 0.05) , and the effect values were 0.554, 0.247 and 0.138, respectively. Perceived risk and effort expectation had effects on performance expectation of patients after PCI ( P<0.05) . Conclusions:Enhancing technical support in various ways, giving play to the publicity role of medical staff, important relatives and friends and new media and improving the ease of use of products can help improve the willingness of patients to use mHealth APP after PCI.

Objective:To investigate the influence of indoxyl sulfate(IS), a typical protein-bound uremic toxin, on left atrial (LA) functional strains using three-dimensional speckle tracking echocardiography (3DSTE).Methods:From May 2019 to January 2020, 128 individuals were consecutively enrolled, including 37 healthy controls and 91 patients, who received maintenance hemodialysis (MHD) in the blood purification center of Zhongshan Hospital affiliated to Fudan University. Conventional echocardiographic parameters and 3DSTE datas of LA were obtained on interdialytic days.LA reservoir, conduit and contraction strains (LASr, LAScd and LASct) were calculated and compared. IS concentration in plasma was assessed by high-performance liquid chromatography tandem mass spectrometry in the MHD cohort.According to the IS concentration, the MHD group was divided into high and low IS (HI and LI) groups. The LA data were also compared between the two groups and linear regression analysis was used to identify independent impact factors of LA strains.Results:Compared to the control group, MHD group had markedly enlarged LA volumes( P<0.05). With regard to the LA phasic strains, both of LASr and LAScd were decreased( P<0.05), while LASct remained unchanged( P>0.05). Compared to the LI group, LASr, LAScd and LASct of the HI group were significantly decreased(all P<0.05). Correlation analysis showed IS concentration correlated well with LASr( rs=-0.674, P<0.001), LAScd( rs=0.454, P<0.001) and LASct( rs=0.376, P<0.001). After adjustment of age, systolic blood pressure, left ventricular mass index(LVMI), and pulmonary systolic pressure, IS concentration remained independently associated with LASr (β=-0.206, 95% CI=-0.353--0.059, P=0.007). Conclusions:In MHD patients, LA is enlarged, and its reservoir function and conduit function are impaired.LA strains derived from 3DSTE are independently related to the IS concentration in plasma, which can be used for the monitoring and evaluation of IS induced cardiac injury.