摘要
To characterize human antibodies against low-calcium response V(LcrV)antigen of Yersinia pestis,the mono-clonal antibodies were screened and assayed.Antibody gene was derived from peripheral blood mononuclear cells of the vaccin-ees immunized by plague subunit vaccine in phase Ⅱb clinical trial.Human ScFv antibody library was constructed by phage dis-play.After panning library by using recombinant LcrV antigen,antibody variable genes were sequenced and converted into IgG1 format to evaluate its binding specificity and relevant parameters.An anti-plague human ScFv antibody library was estab-lished contained 7.54× 108 independent clones.After panning by LcrV antigen,3 human antibodies named as RV-B4,RV-D1 and RV-E8,respectively,were identified.Using indirect enzyme-linked immunosorbent assay(ELISA)and Western blot(WB),the specific bindings of the mAbs to LcrV antigen were confirmed.The dissociation constant(KD)of them to LcrV is 2.1 nmol/L,1.24 nmol/L and 42 nmol/L,respectively.Minor protective efficacy was found among 3 human antibodies in Y.pestis 141-infected mice.Three anti-LcrV monoclonal antibodies generated from immunized vaccinees were binding specific antibod-ies and could not block plague infection in mice.These antibodies are the potential candidate reagents for basic research of plague immunity and the application of plague diagnosis.
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Objective:To evaluate clinical prognosis and prognostic factors of patients with early stage (Ⅰ stage) and locally advanced (Ⅱ/Ⅲ stage) lung cancer treated with carbon ion radiotherapy (CIRT).Methods:Clinical data, treatment, adverse reactions, survival and so on of 54 lung cancer patients who received CIRT and follow-up in the Heavy Ion Center of Wuwei Cancer Hospital of Gansu Province from March 2020 to September 2022 were retrospectively analyzed. The survival curve was plotted using Kaplan-Meier method. Difference tests were performed using log-rank test. Logistic regression analysis was used to identify prognostic factors.Results:According to inclusion and exclusion criteria, 54 patients were enrolled in the study, including 10 patients with early stage lung cancer and 44 patients with locally advanced lung cancer. The median follow-up time for 10 patients with early stage lung cancer was 11.0 (6.75, 17.25) months, and the median dose of irradiation was 60 Gy [relative biological effect (RBE)]. Upon the last follow-up, 3 patients had complete response (CR) and 3 patients had partial response (PR). Four patients had stable disease (SD) and no progressive disease (PD). The 1-year and 2-year local control rates (LCR), progression-free survival (PFS) rates and overall survival (OS) rates were 100%. During treatment and follow-up, 2 patients developed grade 1 radiation pneumonia, 1 case of grade 2 radiation pneumonia, 1 case of chest wall injury (chest wall pain), and there were no adverse reactions greater than grade 2. The median follow-up time of 44 patients with locally advanced stage was 12.5 (4.25, 21.75) months, and the median irradiation dose was 72 Gy (RBE). Thirty-two (73%) patients received concurrent chemotherapy during treatment, 20 (45%) patients received sequential chemotherapy after treatment, 14 (32%) patients received immune maintenance therapy and 3 (7%) patients obtained PD and received targeted drugs. Upon the last follow-up, 3 (7%) patients had CR, 17 (39%) patients had PR, 19 (43%) patients obtained SD, and 5 (11%) patients had PD. The 1-year and 2-year LCR were 96.0% and 87.3%, 90.9% and 84.1% for the 1-year and 2-year PFS rates, and 93.2% and 86.4% for the 1-year and 2-year OS rates, respectively. The median OS and PFS of patients were not reached. Multivariate logistic regression analysis showed that maintenance therapy after radiotherapy ( P=0.027) and clinical target volume (CTV) irradiation volume ( P=0.028) were the factors affecting PFS. Simultaneous chemoradiotherapy ( P=0.042) and maintenance therapy after radiotherapy ( P=0.020) were the factors affecting OS. And gross tumor volume (GTV) ≥215 ml ( P=0.068) might be an independent risk factor for grade 2 and above radiation pneumonia. Conclusions:The domestic carbon ion system has definite clinical effect and controllable toxic and side effects in the treatment of early stage and locally advanced lung cancer. The combination of synchronous chemotherapy and further maintenance treatment can significantly improve clinical prognosis of patients without significantly increasing the risk of toxic and side effects.
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Objective: To explore the long-term clinical efficacy of transcatheter repair of mitral paravalvular leak (PVL) post surgical mitral valve replacement. Methods: This study is a retrospective study. Patients who completed transcatheter repair of paravalvular leak after surgical mitral valve replacement at Shanghai Chest Hospital, Shanghai Jiaotong University School of Medicine from March 2010 to December 2018 were included. Technical success was defined as the occluder being stably implanted in the paravalvular leak site without affecting the function of the mitral valve and surrounding tissues; and there were no intervention-related complications, such as new hemolysis or aggravated hemolysis, and echocardiography confirmed mitral paravalvular regurgitation reduced by more than 1 grade. Patients were followed up at 30 days, 1, and 3 years after the intervention. The main endpoints were all-cause death and re-surgery due to interventional failure or serious complications. The occurrence of occluder-mediated hemolysis and chronic renal insufficiency was recorded, and patients were monitored with echocardiography during follow up. Results: A total of 75 patients were included, aged (54.3±22.9) years old, and 38 patients were males. All patients had decreased cardiac function and/or hemolysis before intervention. Procedural success was achieved in 54 patients (72.0%). Incidence of device-mediated hemolysis was 18.7% (14/75). During the follow-up period, all-cause death occurred in 7 patients (9.3%), and 3 were cardiac deaths.The 3-year event-free survival rate was 81.3% (61/75). The need for cardiac surgery was 9.3% (7/75): 3 cases due to severe device-mediated hemolysis, 2 cases due to prosthetic valve failure and 2 cases due to moderate to severe residual regurgitation. The echocardiography follow-up results showed that the position of the occluder was stable, there was no impact on the artificial valve function and surrounding structures, and the residual regurgitation was stable without progressive increase in event-free patients. Compared with pre-intervention, the left ventricular end systolic diameter ((33.9±7.4)mm vs. (38.3±8.9) mm, P=0.036), end diastolic diameter ((53.7±8.3) mm vs. (58.4±9.1) mm, P=0.045) and left atrial diameter (59.3 (44.5, 90.7) mm vs. 64.3 (44.8, 96.6) mm, P=0.049) were significantly reduced, pulmonary artery systolic pressure was also significantly decreased ((36.5±15.8) mmHg vs. (46.3±14.9) mmHg, P=0.022, 1 mmHg=0.133 kPa). There was no significant difference between 3 years and 1 year after transcatheter repair of mitral paravalvular leak post surgical mitral valve replacement (all P>0.05). Conclusion: Transcatheter repair of mitral paravalvular leak post surgical mitral valve replacement is an effective treatment option in selective patients.
Subject(s)
Male , Humans , Adult , Middle Aged , Aged , Female , Mitral Valve/surgery , Heart Valve Prosthesis Implantation , Heart Valve Prosthesis , Retrospective Studies , Hemolysis , China , Mitral Valve Insufficiency/surgery , Treatment Outcome , Cardiac Catheterization , Prosthesis Failure摘要
Objective:To compare the adverse reactions, efficacy and survival rate of carbon ion beam irradiation in the elective lymph node (ENI) drainage area of locally advanced non-small cell lung cancer (LA-NSCLC) with relative biological effect (RBE) dose of 48 Gy using 16 and 12 fractions.Methods:A total of 72 patients with pathologically confirmed LA-NSCLC admitted to Wuwei Heavy Ion Center of Gansu Wuwei Tumor Hospital from June 2020 to December 2021 were enrolled and simple randomly divided into groups A and B, with 36 patients in each group. Patients in groups A and B were treated with carbon ion beam irradiation to the lymph node drainage area with 48 Gy (RBE) using 16 and 12 fractions. The acute and chronic adverse reactions, efficacy and survival rate were observed. The survival curve was drawn by Kaplan-Meier method. Difference test was conducted by log-rank test.Results:The median follow-up time was 13.9 (8.8-15.7) months in group A and 14.6 (6.3-15.9) months in group B. Sixteen (44.4%) patients were effectively treated in group A and 9 (25%) patients in group B. Thirty-four (94.4%) cases achieved disease control in group A and 30 (83.3%) cases in group B. Statistical analysis showed that the overall survival rate in group B was similar to that in group A ( χ2=1.192, P=0.275). Comparison of planning parameters between two groups showed CTV volume, D mean, V 5 Gy(RBE), V 20 Gy(RBE) and V 30 Gy(RBE) of the affected lung, cardiac V 20 Gy(RBE), V 30 Gy(RBE) and D mean, esophageal V 30 Gy(RBE), V 50 Gy(RBE), D max and D mean, D max of the trachea and spinal cord had no significant difference (all P>0.05). No grade 3 or 4 adverse reactions occurred in the enrolled patients during treatment and follow-up. No statistical differences were observed in the acute radiation skin reaction ( χ2=5.134, P=0.077), radiation esophagitis ( χ2=1.984, P=0.371), and advanced radiation pneumonia ( χ2=6.185, P=0.103) between two groups. Conclusions:The two dose fractionation modes of carbon ion therapy system are equally safe in the mediastinal lymphatic drainage area of LA-NSCLC, and the adverse reactions are controllable. The long-term efficacy still needs further observation.
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BACKGROUND@#Human umbilical cord mesenchymal stem cells (hUCMSCs) have emerged as promising therapy for immune and inflammatory diseases. However, how to maintain the activity and unique properties during cold storage and transportation is one of the key factors affecting the therapeutic efficiency of hUCMSCs. Schisandrin B (SchB) has many functions in cell protection as a natural medicine. In this study, we investigated the protective effects of SchB on the hypothermic preservation of hUCMSCs. @*METHODS@#hUCMSCs were isolated from Wharton’s jelly. Subsequently, hUCMSCs were exposed to cold storage (4 °C) and 24-h re-warming. After that, cells viability, surface markers, immunomodulatory effects, reactive oxygen species (ROS), mitochondrial integrity, apoptosis-related and antioxidant proteins expression level were evaluated. @*RESULTS@#SchB significantly alleviated the cells injury and maintained unique properties such as differentiation potential, level of surface markers and immunomodulatory effects of hUCMSCs. The protective effects of SchB on hUCMSCs after hypothermic storage seemed associated with its inhibition of apoptosis and the anti-oxidative stress effect mediated by nuclear factor erythroid 2–related factor 2 signaling. @*CONCLUSION@#These results demonstrate SchB could be used as an agent for hypothermic preservation of hUCMSCs.
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With the development and application of laparoscopic hepatectomy in major medical centers, domestic and foreign guidelines have summarized the indications, surgical techniques and operational procedures of the surgery. But in primary care facilities, where the surgical equipment are available, laparoscopic hepatectomy is performed only in a small number of cases and the progress of its application remains slow. The reasons possibly lie in the failure of a full understanding of the surgery, the lack of anatomical knowledge of laparoscopic hepatectomy, the lack of close multidisciplinary cooperation in the perioperative period and insufficient training of laparoscopic technology. In this review, we elaborate on three aspects of laparoscopic hepatectomy: preoperative planning, surgical techniques and postoperative management. Before the operation, the surgeons should fully understand the anatomical structure of the liver and select appropriate cases considering both the difficulty of operation and the surgical experience of the surgeons. During the operation, the position of the patient and the layout of the stamping card should be appropriate, and the central venous pressure needs to be well controlled in close cooperation with the anesthesiologist. The surgeons should be proficient at the techniques of liver suspension and pulling and at the use of ultrasonic knife, and select correct techniques for management of bleeding and the control of blood flow in and out of the liver. The patient should receive postoperative management with standard enhanced recovery after surgery (ERAS) protocols. These experiences may help to improve the practice of laparoscopic hepatectomy in local hospitals or primary care facilities.
Subject(s)
Humans , China , Hepatectomy , Laparoscopy/methods , Liver Neoplasms/surgery , Postoperative Period , Primary Health Care摘要
Objective: To evaluate the short-term efficacy and perioperative safety of catheter-based intervention in patients with pulmonary vein stenosis caused by fibrosing mediastinitis (FM). Methods: It was a case series study. Consecutive patients with pulmonary vein stenosis caused by FM, who underwent percutaneous pulmonary vein angioplasty in Gansu Provincial Hospital from January 2018 to June 2020, were retrospective enrolled. The baseline characteristics, comorbidities, exercise capacity and hemodynamic data before and after treatment were compared, and the procedural related complications were evaluated. Results: A total of 30 patients ((64.3±7.1) years, 15 males) were included. Sixty-three pulmonary vein stenosis were treated by 32 percutaneous pulmonary vein angioplasty procedures. Forty-four stents were implanted in 41 pulmonary veins after balloon angioplasty, and the diameter of implanted stents was (8.3±1.2)mm. Balloon angioplasty was performed on 22 pulmonary vein stenosis, the mean balloon diameter was (4.2±2.1)mm. The pulmonary vein diameter increased from (2.6±1.3) to (6.6±2.6) mm (P<0.001) and the pressure gradient across the pulmonary vein stenotic segment reduced from 19 (12, 29) to 2 (0, 4) mmHg (1 mmHg=0.133 kPa) (P<0.001) immediately post procedure. The pulmonary vein flow grade was significantly improved compared with baseline (P<0.001). The most common operation related complications were lung injury (44.0% (11/25)) and hemoptysis (18.8% (6/32)), which did not need special treatment. During the 2.0 (1.3, 3.2) months follow-up, the WHO functional class was significantly improved (P<0.05), the 6-minute walking distance increased from (254.8±114.5) m to (342.8±72.4)m (P<0.05), the mean pulmonary arterial pressure decreased from (40.9±8.3) mmHg to (35.4±7.7) mmHg (P<0.01), 17 out of 19 patients with refractory pleural effusion experienced total remission during the follow-up period (P<0.001). CT pulmonary venography was repeated in 17 patients. The incidence of in-stent restenosis of pulmonary vein was 24.0% (6/25). Conclusions: Percutaneous pulmonary vein angioplasty is effective for the treatment of pulmonary vein stenosis caused by fibrosing mediastinitis. However, it's not so safe, procedural related complication should be paid attention to and the rate of in-stent restenosis is relative high during the short-term follow-up.
Subject(s)
Humans , Male , Angioplasty, Balloon , Catheters , Mediastinitis , Retrospective Studies , Sclerosis , Stenosis, Pulmonary Vein , Stents , Treatment Outcome摘要
Takayasu′s arteritis (TAK) mainly involves the aorta and its major branches, which is characterized as a chronic, progressive and inflammatory disease. China belongs to one of the regions with a high prevalence of TAK referring to its global distribution. However, it is insufficient for the spread and update of standardized diagnosis and treatment of TAK. Based on the evidence and guidelines from China and other countries, Chinese Rheumatology Association developed the standardized diagnosis and treatment of TAK in China. The purpose is to standardize the methods for diagnosis of TAK, assessment of disease activity and disease severity, strategies of internal treatment and timing of surgical intervention, and further leading to protect the function of important organs and improve the disease prognosis.
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Objective:To evaluate the feasibility and safety of carbon ion radiotherapy (CIRT) in the treatment of muscle-invasive bladder cancer in phase Ⅰ/Ⅱ clinical trials.Methods:Clinical stage T 2-3 patients with muscle-invasive bladder cancer (without distant metastasis) were studied. A three-fraction treatment was applied, including the local irradiation with the dose from 12 Gy to 24 Gy and 11 fractions of whole-bladder irradiation with a dose of 44 Gy. The carbon ion irradiation dose is determined with relative biological effectiveness (RBE) of 3.0. The total dose for bladder tumor was 56-68 Gy in 14 fractions. The primary endpoints included tumor treatment-related side effects, dose-limiting toxicity (DLT) responses, and local control (LC) rate, and the secondary endpoints included progression-free survival (PFS). Results:Nine patients received CIRT of various doses in the clinical trials, with the dose gradually increasing to 68 Gy. The patients did not suffer from DLT response, acute adverse effects of radiation therapy of grade ≥3, and late radiation adverse reactions during follow-up. When the dose to the tumor reached 68 Gy, there were 2 cases of grade 2 acute urogenital tract reaction and 1 case of acute lower gastrointestinal tract symptom. For the group with a dose above 62 Gy, three cases of grade 1 late radiation bladder reaction were observed and their symptoms included urinary frequency and microscopic hematuria. At the end of treatment, hematuria disappeared, dysuria was relieved, and urine red blood cell value significantly decreased for all the patients. Three months and six months after treatment, the LC rates were 100% and 88.9%, respectively, and the objective response rates were both 88.9%. One patient developed local recurrence and was treated with salvage surgery six months after treatment.Conclusions:The preliminary efficacy observation of CIRT in the treatment of muscle-invasive bladder cancer showed significant short-term efficacy, obvious symptom relief, and good tolerability for patients, without DLT. Therefore, CIRT is safe and feasible.
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Vaccination is an effective way to reduce the morbidity and mortality of infectious diseases. As a needle-free transcutaneous immunization (NF-TCI) vaccination technology, microneedles (MNs), composed of multiple micro-needles orderly attached to a substrate, can overcome the problems of low immune efficiency, poor compliance and waste of resources that exists in the conventional vaccination by injection, thus becoming a research hotspot in biomedicine. The microneedle vaccine can directly break through the stratum corneum barrier of the skin without touching nerves and blood vessels in the dermis, and effectively delivers the vaccine to the immune cells in the skin tissue to initiate the immune response of the body, thus triggering strong humoral and cellular immune processes. Vaccine delivery via the MNs system possesses the advantages of high safety, satisfying immune effect and practical economy, and shows great prospect in the prevention and treatment of infectious diseases and antineoplastic therapy. This article reviews the development background of MNs in transcutaneous immunization, the types of vaccine delivery, the factors affecting the immune effect, the problems to be solved and development direction in the future.
摘要
Dry powder inhalers (DPIs) had been widely used in lung diseases on account of direct pulmonary delivery, good drug stability and satisfactory patient compliance. However, an indistinct understanding of pulmonary delivery processes (PDPs) hindered the development of DPIs. Most current evaluation methods explored the PDPs with over-simplified models, leading to uncompleted investigations of the whole or partial PDPs. In the present research, an innovative modular process analysis platform (MPAP) was applied to investigate the detailed mechanisms of each PDP of DPIs with different carrier particle sizes (CPS). The MPAP was composed of a laser particle size analyzer, an inhaler device, an artificial throat and a pre-separator, to investigate the fluidization and dispersion, transportation, detachment and deposition process of DPIs. The release profiles of drug, drug aggregation and carrier were monitored in real-time. The influence of CPS on PDPs and corresponding mechanisms were explored. The powder properties of the carriers were investigated by the optical profiler and Freeman Technology four powder rheometer. The next generation impactor was employed to explore the aerosolization performance of DPIs. The novel MPAP was successfully applied in exploring the comprehensive mechanism of PDPs, which had enormous potential to be used to investigate and develop DPIs.
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Objective:To investigate the influencing factors of headache degree in migraine patients with patent foramen ovale (PFO).Methods:The clinical data of 124 migraine patients with PFO from January 2013 to June 2019 in Dalian Central Hospital Affiliated to Dalian Medical University were retrospectively analyzed. The right-to-left shunt of PFO was assessed by contrast-enhanced transcranial Doppler (c-TCD); the diameter of PFO, length of PFO tunnel and the presence of atrial septal aneurysm (ASA) were detected by transesophageal echocardiography (TEE); the degree of migraine was assessed by headache impact test-6 (HIT-6) scale. The relations between right-to-left shunt volume of PFO, diameter of PFO and degree of migraine were analyzed by Goodman-Kruskal γ test; the relations between the length of PFO tunnel, ASA and degree of migraine were analyzed by Spearman rank correlation analysis.Results:Among the 124 migraine patients with PFO, the c-TCD test result showed that small shunt volume was in 20 cases, medium shunt volume in 31 cases, and large shunt volume in 73 cases. The TEE test result showed that small foramen ovale in 76 cases, medium foramen ovale in 47 cases, and large foramen ovale in 1 case; long tunnel in 57 cases, and short tunnel in 67 cases; without ASA in 91 cases, and with ASA in 33 cases. The HIT-6 score result showed that some influence in 9 cases, significantly influence in 22 cases, and serious influence in 93 cases. The Goodman-Kruskal γ test result showed that right-to-left shunt volume of PFO and diameter of PFO were positive correlation with degree of migraine ( γ = 0.66, P<0.01; γ = 0.38, P<0.05). The Spearman rank correlation analysis result showed that ASA was positive correlation with degree of migraine ( r = 0.18, P<0.05), while the length of PFO tunnel was negative correlation with degree of migraine ( r = -0.23, P<0.05). Conclusions:The right to left shunt amount of PFO, diameter of PFO and the presence of ASA are positive correlation with degree of migraine, while the length of PFO tunnel is negative correlation with degree of migraine.
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Objective:To explore the possible mechanism of exacerbation of anxiety-like behavior in db/db mice after distal middle cerebral artery occlusion (dMCAO).Methods:The db/db mice was used to establish a type 2 diabetes mellitus model. Meanwhile, heterozygous db/+ mice and C57 wild-type (WT) mice were chosen as double control groups. Then a permanent distal middle cerebral artery occlusion model was employed as an acute ischemic stroke model. The blood glucose levels before and post-dMCAO surgery on day1, day3, and day5 were detected. The brain tissue loss at 35 days after stroke was measured by immunofluorescent staining of MAP2. The open-field test was performed to estimate anxiety-like behavior and general motor and exploring ability of the animals. Axons and myelin were immunostained with non-phosphorylated neurofilaments (SMI32) and myelin basic protein (MBP), respectively, to evaluate differences in white matter integrity in WT, db/+ and db/db mice 35 days after stroke. The correlation between SMI32/MBP and open field test parameters (time in center and corner) was analyzed. Flow cytometry was employed to detect the amount of T cells and B cells, including regulatory T cells (Tregs) in the brain tissue.Results:Blood glucose levels in db/db mice were significantly higher than db/+ mice and WT mice in both sham and dMCAO groups ( P<0.01). There was no significant difference in brain tissue loss 35 days post-stroke among db/db mice, db/+ mice, and WT mice. In the open field test, there were significant differences in the total distance of db/db mice, db/+ and WT mice in the sham and dMCAO groups. Db/db mice shorter than db/+ mice ( P<0.05), WT mice ( P<0.01), and db/+ mice shorter than WT mice ( P<0.05). There were significant time differences in the center among db/db, db/+, and WT mice in sham and dMCAO groups. In both the sham and dMCAO groups, db/db mice spent less time in the center area of the open field than WT mice ( P<0.01). In the sham group, db/+ mice spent less time in the center area than WT mice ( P<0.05). In dMCAO group, db/db mice spent less time in the center area than db/+mice ( P<0.05), and db/+ mice spent less time in the center area than WT mice ( P<0.01). For the time in the corner, in both the sham and dMCAO groups, db/db mice and db/+ mice consumed more time than WT mice ( P<0.01 or <0.05). In the dMCAO group, db/db mice spent more time in the corner than db/+ mice ( P<0.05). Referring to white matter injury, an increased SMI32/MBP ratio in EC area and CTX area (data was not shown in this article) after dMCAO in db/db, db/+ and WT mice were detected. In EC area, db/db mice have a higher SMI32 ratio than db/+ mice and WT mice: 4.24 ± 0.37 vs. 1.96 ± 0.37, 1.80 ± 0.36, both have significant differences ( P<0.01). For db/db mice and WT mice, the SMI32/MBP ratio negatively correlates with time in center and positive correlation with time in the corner. Three days after dMCAO, the total cells of CD 3+ T cells, CD 8+ cells, Tregs, in db/db mice group have significantly decreased compared to WT group: 4 079 ± 1 345 vs. 70 055 ± 3 374, 141.30 ± 28.36 vs. 2 714.00 ± 463.20, 148.00 ± 61.15 vs. 3 007.00 ± 639.90 ( P<0.01), while B cell has no change between two groups. Conclusions:By comparing the severity of anxiety-like behavior of db/db mice, the severity of white matter injury, and the number of T cells and B cells in brain tissue after dMCAO, immune-mediated brain white matter injury may aggravate db/db mice′s post-dMCAO anxiety-like behavior. Due to the gene dose effect, db/+ mice are not suitable as a control group for db/db mice in animal experiments involving anxiety-like behavior assessment.
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Kallmann syndrome(KS) is a subtype of idiopathic hypogonadotropic hypogonadism(IHH), characterized by delayed puberty, undeveloped secondary sexual characters, accompanied by anosmia, or hyposmia. At present, more than 40 genes are related to the pathogenesis of IHH, and new gene loci have been found continuously. At the same time, digenic gene mutation or oligogenic mutation is considered to be an important pathogenic mechanism of IHH. The clinical phenotype of KS/IHH caused by different gene mutations is complex and diverse, and the response to treatment is also variable. This paper presents the clinical data and treatment of a case of KS caused by a compound double heterozygous mutation of WDR11 and PROKR2 genes. PROKR2 gene is a classic KS pathogenic gene, while the WDR11 gene is a relatively new type of KS pathogenic gene. Included with this case report is a literature review of characteristics of cases with WDR11 gene mutation.
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When nanoparticles were introduced into the biological media, the protein corona would be formed, which endowed the nanoparticles with new bio-identities. Thus, controlling protein corona formation is critical to
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Objective:To analyze the correlation factors between peripapillary duodenal diverticulum (PDD) and choledochectasia by CT scan.Methods:The clinical data of 220 patients with duodenal diverticulum detected by multi-slice spiral CT scan and confirmed by gastrointestinal angiography or endoscopic retrograde cholangiopancreatography (ERCP) in Dahua Hospital, Xuhui District of Shanghai City were retrospectively analyzed. The correlation of the PDD, the contact of common bile duct (CBD), length of contact and exudation with choledochectasia in patients with PDD were analyzed.Results:A total of 236 duodenal diverticulum were found in 220 patients. Among them, there were 152 PDD, 41 diverticulum located superior to the duodenal papilla, 28 diverticulum located inferior to the duodenal papilla, 3 diverticulum located lateral to the duodenal papilla, and 12 diverticulumlocated in the horizontal portion. The incidence of choledochectasia in patients with PDD contacted with CBD was significantly higher than that in patients with PDD not contacted with CBD: 59.35% (73/123) vs. 37.93% (11/29), and there was statistical difference ( P<0.05); the incidence of choledochectasia in patients with contact length of PDD and CBD ≥1.5 cm was significantly higher than that in patients without contact of PDD and CBD and patients with contact length of PDD and CBD <1.5 cm: 82.43% (61/74) vs. 24.49% (12/49) and 37.93% (11/29), and there was statistical difference ( P<0.05); the incidence of choledochectasia in PDD patients with exudation was significantly higher than that in PDD patients without exudation: 10/11 vs. 52.48% (74/141), and there was statistical difference ( P<0.05). Conclusions:The patients with contact length of PDD and CBD ≥1.5 cm and patients with PDD combined with exudation could be prone to choledochectasia.
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Objective:To investigate the influence of Covid-19 epidemic on the number of acute ischemic stroke patients with intravenous thrombolytic therapy in Dalian in 2020, the way to hospital, onset to door time (ODT), door to needle time(DNT), onset to needle time(ONT), and the National Institute of Health Stroke Scale (NIHSS) before and after intravenous thrombolytic therapy.Methods:This was a retrospective descriptive study on 13 map-participating hospitals in Dalian from August 2020 to December 2020. The number of acute ischemic stroke patients with intravenous thrombolytic therapy, ODT, DNT, ONT, modes of transport to hospital, the NIHSS score before and after intravenous thrombolytic therapy, etc were analyzed. Data were collected from August 1, 2020 to December 31, 2020, and compared with the baseline data from the same period in 2019.Results:SPSS 22.0 statistical software and Data Analysis ToolPak were used for statistical analysis of the obtained data, and T tests statistic was used for data analysis. In 2020,the number of acute ischemic stroke patients with intravenous thrombolytic therapy increased (681 cases vs 416 cases), and DNT increased [50 minutes vs 45 minutes P = 0.01]. In 2020, 83.55% of patients indicated self-visit as their main mode of transport to the hospital. In 2020, among the self-visit patients with NIHSS score<15 scores,the number of the patients with the NHISS score unchanged or decreased after intravenous thrombolytic therapy was more (562 scores vs. 535 scores, P<0.001), and the patients with NIHSS score ≥15 scores were more willing to call ambulances to hospital. Conclusions:During the Covid-19 epidemic period of 2020, the number of acute ischemic stroke patients receiving intravenous thrombolytic therapy increased, DNT increase; the patients withNIHSS score<15 scores are more willing to choose to visit the hospital using their own transportation and benefit from intravenous thrombolytic therapy. The patients with NIHSS ≥15 scores prefer to call ambulances to hospital.
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Proteins and peptides have become a significant therapeutic modality for various diseases because of their high potency and specificity. However, the inherent properties of these drugs, such as large molecular weight, poor stability, and conformational flexibility, make them difficult to be formulated and delivered. Injection is the primary route for clinical administration of protein and peptide drugs, which usually leads to poor patient's compliance. As a portable, minimally invasive device, microneedles (MNs) can overcome the skin barrier and generate reversible microchannels for effective macromolecule permeation. In this review, we highlighted the recent advances in MNs-mediated transdermal delivery of protein and peptide drugs. Emphasis was given to the latest development in representative MNs design and fabrication. We also summarize the current application status of MNs-mediated transdermal protein and peptide delivery, especially in the field of infectious disease, diabetes, cancer, and other disease therapy. Finally, the current status of clinical translation and a perspective on future development are also provided.
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Membrane-disruptive peptides/peptidomimetics (MDPs) are antimicrobials or anticarcinogens that present a general killing mechanism through the physical disruption of cell membranes, in contrast to conventional chemotherapeutic drugs, which act on precise targets such as DNA or specific enzymes. Owing to their rapid action, broad-spectrum activity, and mechanisms of action that potentially hinder the development of resistance, MDPs have been increasingly considered as future therapeutics in the drug-resistant era. Recently, growing experimental evidence has demonstrated that MDPs can also be utilized as adjuvants to enhance the therapeutic effects of other agents. In this review, we evaluate the literature around the broad-spectrum antimicrobial properties and anticancer activity of MDPs, and summarize the current development and mechanisms of MDPs alone or in combination with other agents. Notably, this review highlights recent advances in the design of various MDP-based drug delivery systems that can improve the therapeutic effect of MDPs, minimize side effects, and promote the co-delivery of multiple chemotherapeutics, for more efficient antimicrobial and anticancer therapy.
摘要
Nanoparticles (NPs) have shown potential in cancer therapy, while a single administration conferring a satisfactory outcome is still unavailable. To address this issue, the dissolving microneedles (DMNs) were developed to locally deliver functionalized NPs with combined chemotherapy and photothermal therapy (PTT).