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Objectives:To compare the effects of 3D-printed personalized guiding template and robot-assisted pedicle screw placements in orthopedic surgery for adult degenerative scoliosis(ADS).Methods:Retrospective analysis was conducted on 18 ADS patients hospitalized and treated with corrective surgery in the department between January 2020 and December 2022.There were 3 males and 15 females,aged 46-73(63.2±8.2)years old.A total of 236 pedicle screws were placed,and the patients were divided into two groups according to the auxiliary screw placement methods:the 3D-printed personalized guiding template group(3D-printed group,1 1 cases,142 pedicle screws were placed)and robot-assisted screw placement group(Robot group,7 cases,94 pedicle screws were placed).The patients were followed up for 6 months and more.The vertex rotation angle and scoliosis Cobb angle were measured and compared between groups before operation.All pedicle screws were classified by Gertzbein-Robbins classification standard at 1 week after operation,and the accuracy and satisfaction of screw placement in the two groups were compared;And the operative time and incidence of complications were also analyzed and compared between the two groups.Re-sults:The 3D-printed group was not statistically different from the robot group in terms of age(63.6±9.0 years vs.62.6±7.3 years),gender ratio(male/female:2/9 vs.1/6),number of screws placed(12.91±3.83 vs.13.43± 3.60),Cobb angle(40.36°±1 1.82° vs.38.14°±12.84°),and vertex rotation angle(30.27°±7.25° vs.29.86°±9.65°),respectively(P>0.05).The robot group was longer in operative time than that of 3D-printed group(354.29± 53.73min vs.282.27±73.87min,P<0.05).Of the total 142 pedicle screws placed in the 3D-printed group,128 screws were of class A,10 were of class B,and 4 were of class C;Of the total 94 pedicle screws placed in the robot group,86 screws were of class A,5 were of class B,and 3 were of class C;No class D or E screws in the two groups.The accuracy rate of screw placement(90.14%)and satisfaction rate(97.18%)of the 3D-printed group were not statistically different from the accuracy rate(91.49%)and satisfaction rate(96.81%)of the robot group,respectively(P>0.05).The incidence of complications in the 3D-printed group(36.36%)was not significantly different from that in the robot group(57.14%,P>0.05).Conclusions:Both auxiliary screw placement methods can assist spinal surgeons to accurately place screws in ADS patients,but 3D-printed personalized guiding template needs less time in screw placement.
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Mechanical signal transduction are crucial for chondrocyte in response to mechanical cues during the growth, development and osteoarthritis (OA) of articular cartilage. Extracellular matrix (ECM) turnover regulates the matrix mechanical microenvironment of chondrocytes. Thus, understanding the mechanotransduction mechanisms during chondrocyte sensing the matrix mechanical microenvironment can develop effective targeted therapy for OA. In recent decades, growing evidences are rapidly advancing our understanding of the mechanical force-dependent cartilage remodeling and injury responses mediated by TRPV4 and PIEZOs. In this review, we highlighted the mechanosensing mechanism mediated by TRPV4 and PIEZOs during chondrocytes sensing mechanical microenvironment of the ECM. Additionally, the latest progress in the regulation of OA by inflammatory signals mediated by TRPV4 and PIEZOs was also introduced. These recent insights provide the potential mechanotheraputic strategies to target these channels and prevent cartilage degeneration associated with OA. This review will shed light on the pathogenesis of articular cartilage, searching clinical targeted therapies, and designing cell-induced biomaterials.
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Condrócitos , Canais de Cátion TRPV , Mecanotransdução Celular , Materiais Biocompatíveis , Cartilagem ArticularRESUMO
Objective:To summarize the experience of ambulance medical support in the 19th Hangzhou Asian Games, and provide reference for the ambulance medical support work of large-scale sports events in the future.Methods:According to the actual situation of the Asian Games, the objectives of the medical support were determined according to the principles of highlighting the key points and overall consideration. All kinds of ambulances were allocated according to the principles of combining dynamic and static and regional linkage. The ambulance support was divided into the event side and the city side,with the regional security vehicle as the supplement of the event side and the guarantee of the city side, the implementation of "one pavilion one policy", "one game one policy", "one place one policy" and "one vehicle one plan", and the interconnection of medical points (rooms), designated hospitals, management and command personnel and ambulances were realized through the Asian Games Intelligent Emergency Medical Support Syetem (EMSS).Results:Between September 16, 2023, 08:00, and October 9, 2023, 08:00, a total of 207 ambulances were deployed during the 19th Hangzhou Asian Games. Of these, 88 (42.5%) were at competition venues, 11 (5.3%) at training venues, 30 (14.5%) at non-competition venues, and 78 (37.7%) were regional support vehicles. Among them, 20 venue ambulances participated in regional support tasks during idle times. Ambulances transported patients from event sites 345 times, with the highest number of transports occurring at competition venues (187 times) and the fewest in the assisting city of Huzhou (6 times). The highest ambulance utilization rate was 70.5% at competition venues, while training venues, non-competition venues, and regional support ambulances had utilization rates of 45.5%, 53.3%, and 42.3%, respectively. The median age of transported individuals was 26 (21, 36), with a majority being male (59.1%). Athletes comprised 52.5% of transports, while staff and spectators accounted for 39.7% and 7.8%, respectively. Joint injuries were the most common condition among transported individuals, totaling 58 cases (16.8%). Regional support ambulances participated in 75 transfers and replacements, with 17 (22.7%) transfers and 58 (77.3%) replacements.Conclusions:This study confirms the feasibility and efficiency of the Asian Games' ambulance support plan, highlighting the crucial role of EMSS. The study suggests the need to strengthen medical support for staff, in addition to athletes.
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Objective:To understand the in vitro antimicrobial resistance and resistance phenotypes profile of Streptococcus suis strains isolated from human in Zhejiang Province. Methods:The strains of sporadic Streptococcus suis infections were isolated during 2005 to 2021 in Zhejiang Province, and were subjected to antimicrobial resistance analysis using agar dilution method. Polymerase chain reaction (PCR) technology was also used to detect 70 resistance genes including tetracyclines, macrolides and aminoglycosides. Results:The results of antimicrobial resistance analysis showed that these strains were sensitive to eleven kinds of antimicrobial agents with a sensitivity rate ≥96.8%, including cefepime, cefotaxime, ceftriaxone, chloramphenicol, daptomycin, ertapenem, levofloxacin, linezolid, meropenem, penicillin and vancomycin. These strains were mainly resistant to tetracycline, clindamycin, azithromycin and erythromycin, especially resistant to tetracycline with a rate of 93.5%(29/31). Fourteen strains (45.2%) exhibited multidrug resistant patterns. The PCR analysis of 70 drug resistance genes showed that 14(20.0%) different resistance genes were detected. The highest detection rate of resistant genes came from tetracycline, including tet ( O) gene (58.1%, 18/31), tet ( M) gene (48.4%, 15/31), tet ( 40) gene (35.5%, 11/31), followed by ermB gene (41.9%, 13/31) in the class of macrolide. Fourteen strains (45.2%) with more than three drug resistance genes were detected, of which eight strains (25.8%) detected 10 drug resistance genes. The analysis of antibiotic resistance and resistance phenotypes profile showed that tet ( M)+ ST7 accounted for 35.5%(11/31), tet( O)+ tet( 40)+ ermB+ mef( A)+ mef( A/ E)+ msrD+ Ant( 6)- Ⅰb+ aph( 3′)- Ⅲa+ aadB+ sat4+ ST7 accounted for 25.8%(8/31). Conclusions:The antimicrobial resistance and resistance phenotypes profile of sporadic Streptococcus suis strains isolated from human in Zhejiang Province are endemic, with mainly two types of characteristic genetic cloning of drug resistance genes.
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Ischemic stroke (IS) is a severe cerebrovascular disease with a high incidence, mortality, and disability rate. The first-line treatment for IS is the use of recombinant tissue plasminogen activator (r-tPA). Regrettably, numerous patients encounter delays in treatment due to the narrow therapeutic window and the associated risk of hemorrhage. Traditional Chinese medicine (TCM) has exhibited distinct advantages in preventing and treating IS. TCM enhances cerebral microcirculation, alleviates neurological disorders, regulates energy metabolism, mitigates inflammation, reduces oxidative stress injuries, and inhibits apoptosis, thereby mitigating brain damage and preventing IS recurrence. This article summarizes the etiology, pathogenesis, therapeutic strategies, and relationship with modern biology of IS from the perspective of TCM, describes the advantages of TCM in the treatment of IS, and further reviews the pharmacodynamic characteristics and advantages of TCM in the acute and recovery phases of IS as well as in post-stroke complications. Additionally, it offers valuable insights and references for the clinical application of TCM in IS prevention and treatment, as well as for the development of novel drugs.
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Modern medicine has made remarkable achievements in safeguarding people's life and health, however, it is increasingly found that in the face of complex diseases, selective targeting of single target is often difficult to produce a comprehensive rehabilitation effect, and is prone to induce drug resistance, toxic side effects. Traditional Chinese medicine (TCM) has a long history of clinical application, and its clinical value in the treatment of complex diseases such as cardiovascular and cerebrovascular diseases, digestive diseases, skin diseases, rheumatism and immunity diseases, and adjuvant treatment of tumors has been proven to have obvious advantages. However, its modern research is relatively lagging behind, and in the face of the aging society and the characteristics of the modern disease spectrum, the traditional knowledge-driven research paradigm seems to be stuck in a bottleneck and difficult to make greater breakthroughs. Focusing on the key issues of TCM development in the new era, the clinical value-oriented strategy becomes to be a new research paradigm of TCM inheritance and innovation development, and dominant diseases would be the focus of the TCM inheritance and innovation development, which has been highly valued in recent years by the TCM academia and the relevant national management departments. Based on the clinical value, a series of policies are formulated for the selection and evaluation of the TCM dominant diseases (TCMDD), and exploratory researches about the clinical efficacy characteristics, the modern scientific connotation interpretation were carried out. The clinical value-oriented research paradigm of TCMDD inheritance and innovation development has been initially formed, which is characterized by strong policy support as the guarantee, systematic and standardized selection and evaluation methods as the driving force, scientific and effective research on internal mechanisms as the expansion, and effective clinical guidelines and principles as the transformation, which is of great value in promoting the high-quality development of the industries and undertaking of TCM. In this paper, the main policy support, selection and evaluation methods, therapeutic effect characterization, and modern scientific connotation research strategies of TCMDD in recent years have been comprehensively sorted out, with a view to providing the healthy and benign development of the research on TCMDD.
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OBJECTIVE To study the effects of Dianxianqing granules on the tau protein in P301S mice by regulating mitophagy. METHODS Totally 36 P301S mice were randomly divided into model group, Dianxianqing granule group (12.48 g/kg), donepezil hydrochloride group (positive control, 1.3 mg/kg), with 12 mice in each group; another 10 C57BL6 mice were selected as control group. Administration groups were given relevant drug solutions intragastrically, and control group and model group were given constant volume of water intragastrically. The gavage volume was 20 mL/kg, once a day, for consecutive 5 months. During the experiment, the general condition of mice was observed in each group. After the last medication, the learning and memory ability was determined by Y maze test and Morris water maze test; HE staining was used to observe the morphological changes in brain tissue, and Nissl staining was used to observe the structure of neural cells and the number of Nissl bodies in cerebral tissue. Immunohistochemistry was used to detect the expressions of phospho-tau serine 202/threonine 205 (abbreviated as AT8) in brain tissue. Western blot assay was used to determine the expressions of mitophagy-associated proteins [PTEN-induced putative kinase-1 (PINK1), Parkin, microtubule-associated protein 1 light chain 3B (LC3B), p62], synaptic-associated proteins [postsynaptic density protein-95 (PSD-95), synaptophysin (SYP), and growth-associated protein-43 (GAP-43)] and the phosphorylation of tau protein [expressed by the phosphorylation levels of serine 199 (Ser199) and Ser202] in brain tissue. RESULTS The mice in E-mail:lnzyxyqy2003@163.com model group showed symptoms such as white hair, decreased body mass, and lower limb paralysis, with incomplete hippocampal structures in their brain tissue, as well as incomplete cell membrane edges and cell structures; the spontaneous alternating response rate, the times of crossing platform, the number of Nissl bodies, the protein expressions of PINK1, Parkin, LC3B, SYP, GAP-43, and PSD-95 were decreased significantly, compared with control group; swimming latency (fourth and fifth day), the protein expressions of AT8 and p62,the phosphorylation levels of Ser199 and Ser202 were increased or lengthened significantly, compared with control group (P<0.05 or P<0.01). Compared with model group, the above symptoms and indexes of mice were improved significantly in administration groups (P<0.05 or P<0.01). CONCLUSIONS Dianxianqing granules can effectively improve cognitive impairment in P301S mice,the mechanism of which may be associated with inducing mitochondrial autophagy, reducing the hyperphosphorylation of tau protein, up-regulating the expression of synaptic-associated proteins in brain tissue,and repairing damaged neural cells.
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Objective@#To investigate the seroprevalence and influencing factors of serum neutralizing antibodies among SARS-CoV-2 infected individuals, so as to provide the evidence for developing the health management and COVID-19 vaccination strategy among SARS-CoV-2 infected individuals.@*Methods@#Recovered SARS-CoV-2 infected individuals from January 1st, 2020 to February 10th, 2021 in Zhejiang Province were recruited in March 2021. Participants' demographics, underlying diseases, date of definitive diagnosis and severity of clinical symptoms were collected using questionnaire surveys, and serum neutralizing antibody against SARS-CoV-2 was detected using a fluorescent immunoassay. In addition, factors affecting the seropositivity of neutralizing antibody against SARS-CoV-2 were identified using a multivariable logistic regression model. @*Results@#A total of 559 SARS-CoV-2 infected individuals were enrolled, including 480 confirmed cases and 79 asymptomatic carriers, with an median (interquartile range) age of 47.00 (22.00) years, and all participants had never received COVID-19 vaccination. The median (interquartile range) duration from diagnosis to serum sampling was 387.00 (11.00) days, and the seroprevalence of neutralizing antibody against SARS-CoV-2 was 83.90%. The serum neutralizing antibody against SARS-CoV-2 was all positive 9 months after diagnosis, and the seroprevalence of neutralizing antibody against SARS-CoV-2 appeared no tendency towards a decline with time within 14 months after diagnosis (P>0.05). Multivariable logistic regression analysis showed that women were 1.892 times (95%CI: 1.169-3.064) more likely to produce serum neutralizing antibodies against SARS-CoV-2 than men, and mild, common and severe/critically ill SARS-CoV-2 infected cases were 2.438 (95%CI: 1.305-4.557), 4.481 (95%CI: 2.318-8.663), and 23.525 (95%CI: 2.990-185.068) times more likely to produce serum neutralizing antibodies against SARS-CoV-2 than asymptomatic carrier, respectively.@*Conclusions@#The seroprevalence of neutralizing antibody was 100.00% among SARS-CoV-2 infected individuals within 9 months after diagnosis. Individuals' gender and severity of clinical symptoms correlate with the seroprevalence of neutralizing antibody against SARS-CoV-2.
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Cell cycle plays a crucial role in cell development. Cell cycle progression is mainly regulated by cyclin dependent kinase (CDK), cyclin and endogenous CDK inhibitor (CKI). Among these, CDK is the main cell cycle regulator, binding to cyclin to form the cyclin-CDK complex, which phosphorylates hundreds of substrates and regulates interphase and mitotic progression. Abnormal activity of various cell cycle proteins can cause uncontrolled proliferation of cancer cells, which leads to cancer development. Therefore, understanding the changes in CDK activity, cyclin-CDK assembly and the role of CDK inhibitors will help to understand the underlying regulatory processes in cell cycle progression, as well as provide a basis for the treatment of cancer and disease and the development of CDK inhibitor-based therapeutic agents. This review focuses on the key events of CDK activation or inactivation, and summarizes the regulatory processes of cyclin-CDK at specific times and locations, as well as the progress of research on relevant CDK inhibitor therapeutics in cancer and disease. The review concludes with a brief description of the current challenges of the cell cycle process, with the aim to provide scientific references and new ideas for further research on cell cycle process.
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Quinases Ciclina-Dependentes/metabolismo , Ciclinas/metabolismo , Proteínas Serina-Treonina Quinases , Proteínas de Ciclo Celular/metabolismo , Ciclo Celular/fisiologia , Quinase 2 Dependente de CiclinaRESUMO
Cognitive dysfunction is one of the common central nervous systems (CNS) complications of diabetes mellitus, which seriously affects the quality of life of patients and results in a huge economic burden. The glymphatic system dysfunction mediated by aquaporin-4 (AQP4) loss or redistribution in perivascular astrocyte endfeet plays a crucial role in diabetes-induced cognitive impairment (DCI). However, the mechanism of AQP4 loss or redistribution in the diabetic states remains unclear. Accumulating evidence suggests that peripheral insulin resistance target tissues and CNS communication affect brain homeostasis and that exosomal miRNAs are key mediators. Glucose and lipid metabolism disorder is an important pathological feature of diabetes mellitus, and skeletal muscle, liver and adipose tissue are the key target insulin resistance organs. In this review, the changes in exosomal miRNAs induced by peripheral metabolism disorders in diabetes mellitus were systematically reviewed. We focused on exosomal miRNAs that could induce low AQP4 expression and redistribution in perivascular astrocyte endfeet, which could provide an interorgan communication pathway to illustrate the pathogenesis of DCI. Furthermore, the mechanisms of exosome secretion from peripheral insulin resistance target tissue and absorption to the CNS were summarized, which will be beneficial for proposing novel and feasible strategies to optimize DCI prevention and/or treatment in diabetic patients.
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SARS-CoV-2 spike protein (S) is structurally dynamic and has been observed by cryo-EM to adopt a variety of prefusion conformations that can be categorized as locked, closed and open. The locked conformations feature tightly packed trimers with structural elements incompatible with RBD in "up" position. For SARS-CoV-2 S, it has been shown that the locked conformations are transient under neutral pH. Probably due to their transience, locked conformations remain largely uncharacterized for SARS-CoV-1 S. Intriguingly, locked conformations were the only conformations captured for S proteins of bat and pangolin origin SARS-related coronaviruses. In this study, we introduced x1, x2, and x3 disulfides into SARS-CoV-1 S. Some of these disulfides have been shown to preserve rare locked conformations when introduced to SARS-CoV-2 S. Introduction of these disulfides allowed us to image a variety of locked and other rare conformations for SARS-CoV-1 S by cryo-EM. We identified bound cofactors and structural features that are associated with SARS-CoV-1 S locked conformations. We compare newly determined structures to other available spike structures of Sarbecoviruses to identify conserved features and discuss their possible functions.
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Objective To establish a local human brain 18F-fluorodeoxyglucose positron emission tomography (PET) database with NeuroQ software, and to test its practical value. Methods With NeuroQ software, the PET images of 93 selected subjects were analyzed, and the results were used to create a local normal human database. The metabolism characteristics of the local population were obtained by comparing the original data of the local database with those of the built-in software database, and the difference in case analysis was compared between the two databases. Results Compared with the built-in database, the local database showed the region with high metabolic rate concentrated in the frontal lobe (right superior frontal gyrus: 4.61%, right middle frontal gyrus: 4.49%, left superior frontal gyrus: 3.77%, and left middle frontal gyrus: 3.11%), right posterior cingulate gyrus (6.28%), right inferior parietal lobule (2.46%), left inferior parietal lobule (2.66%), the region with reduced metabolism mainly in the right cerebellum (−3.57%), left cerebellum (−5.27%), and pons (−3.59%). For case analysis, the local database generated results were better consistent with the clinical assessment results of cases. Conclusion Establishment of a local database would eliminate the differences in regions and acquisition conditions, which is of great value to improve the accuracy of diagnosis.
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Objective:To evaluate the role of ecto-5′-nucleotidase (CD73) in endogenous protective mechanism of hepatic ischemia-reperfusion (I/R) injury in mice and the relationship with transforming growth factor beta1 (TGF-β 1)/Smad3 signaling pathway. Methods:Twenty-four SPF healthy male C57BL/6 mice, aged 8-10 weeks, weighing 20-23 g, were divided into 3 groups ( n=8 each) by the random number table method: sham operation group (S group), hepatic I/R group (IR group) and hepatic I/R plus CD73 specific inhibitor group (APCP group). The hepatic hilum was only exposed but not occluded in group S. The hepatic portal was occluded for 30 min followed by reperfusion to develop the model of hepatic I/R in anesthetized animals in group IR.CD73-specific inhibitor APCP 40 mg/kg was intraperitoneally injected, and 10 min later hepatic I/R was performed.Orbital venous blood samples were collected at 6 h of reperfusion for determination of serum alanine transaminase (ALT) and aspartate transaminase (AST) concentrations.Then the mice were sacrificed, and liver tissues were obtained for determination of the expression of CD73, TGF-β 1 and phosphorylated Smad3 (p-Smad3) (by Western blot), contents of interleukin-1β (IL-1β) and tumor necrosis factor-alpha (TNF-α) (by enzyme-linked immunosorbent assay), and content of malondialdehyde (MDA) and activity of superoxide dismutase (SOD) (with a visible spectrophotometer) and for microscopic examination of the pathological changes of liver tissues (with a light microscope). Results:Compared with group S, the concentrations of AST and ALT in serum and contents of IL-1β, TNF-α and MDA in liver tissues were significantly increased, the activity of SOD was decreased, and the expression of CD73, TGF-β 1 and p-Smad3 was up-regulated in IR and APCP groups ( P<0.05). Compared with group IR, the concentrations of AST and ALT in serum and contents of IL-1β, TNF-α and MDA in liver tissues were significantly increased, the activity of SOD was decreased, and the expression of CD73, TGF-β 1 and p-Smad3 in liver tissues was down-regulated in group APCP ( P<0.05). The pathological changes of liver tissues were accentuated in group APCP as compared with group IR. Conclusions:CD73 is involved in the process of endogenous protective mechanism of hepatic I/R injury in mice, which may be related to the regulation of TGF-β 1/Smad3 signaling pathway.
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Objective:To evaluate the role of microRNA-10a (miRNA-10a) in renal ischemia-reperfusion (I/R) injury in mice and the relationship with transforming growth factor beta1 (TGF-β 1)/Smad2 signaling pathway. Methods:Twenty-four SPF healthy male adult C57BL/6 mice, aged 8-10 weeks, weighing 20-25 g, were divided into 4 groups ( n=6 each) by the random number table method: sham operation group (S group), renal I/R group (IR group), renal I/R plus miRNA-10a antagonist group (I group), and renal I/R+ miRNA-10a agonist group (M group). The mouse model of renal I/R was developed by clamping the left renal pedicle for 45 min followed by reperfusion in anesthetized animals.miRNA-10a antagonist and agonist 20 nmol were injected via the tail vein once every 24 h for 3 consecutive days starting from 72 h before surgery in group M and group I, respectively, while the equal volume of normal saline was given instead in S and IR groups.Blood samples were collected from the orbital vein at 24 h of reperfusion to determine the concentrations of the serum creatinine (Scr) and blood urea nitrogen (BUN). Then the mice were sacrificed, and the kidney tissues were taken for determination of the malondialdehyde (MDA) content and superoxide dismutase (SOD) activity, contents of interleukin-1 beta (IL-β) and tumor necrosis factor-alpha (TNF-α) (by enzyme-linked immunosorbent assay), and expression of TGF-β 1 and phosphorylated Smad2 (p-Smad2) (by Western blot) and for microscopic examination of the pathological changes.The damage to the renal tubules was scored. Results:Compared with group S, the concentrations of Scr and BUN, contents of MDA, IL-1β and TNF-α in renal tissues and renal tubular damage score were significantly increased in IR, I and M groups, and the activity of SOD was significantly decreased, and the expression of TGF-β 1 and p-Smad2 was up-regulated in IR and M groups ( P<0.05). Compared with group IR, the concentrations of Scr and BUN, contents of MDA, IL-1β and TNF-α in renal tissues and renal tubular damage score were significantly decreased, the activity of SOD was increased, and the expression of TGF-β 1 and p-Smad2 was down-regulated in group I, and the concentrations of Scr and BUN, contents of MDA, IL-1β and TNF-α in renal tissues and renal tubular damage score were significantly increased, the activity of SOD was decreased, and the expression of TGF-β 1 and p-Smad2 was up-regulated in group M ( P<0.05). Compared with group I, the concentrations of Scr and BUN, contents of MDA, IL-1β and TNF-α in renal tissues and renal tubular damage score were significantly increased, the activity of SOD was decreased, and the expression of TGF-β 1 and p-Smad2 was up-regulated in group M ( P<0.05). Conclusions:miRNA-10a is involved in the process of renal I/R injury and is related to activation of TGF-β 1/Smad2 signaling pathway in mice.
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Recessive dystrophic epidermolysis bullosa (RDEB) is caused by loss-of-function mutations in the COL7A1 gene encoding the α-1 chain of type Ⅶ collagen, leading to reduced or absent expression of basement membrane type Ⅶ collagen (C7) . Currently, there is no effective treatment for this rare disease, and the management is mainly palliative and supportive. Gene therapy is expected to be an effective treatment of RDEB. This review summarizes current strategies of gene therapy in clinical trials for RDEB, as well as their progress, pros and cons, and prospects.
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Epimedii Herba is a commonly used traditional Chinese herbal medicine. Five Epimedium species are included in Chinese Pharmacopoeia and most species of Epimedium are used as Epimedii Herba in practical application. However, as the largest herbaceous genus of the Berberidaceae, Epimedium has many taxonomic controversies which hinder the effective use of Epimedii Herba. This paper reviewed the taxonomic research related to Epimedium, including taxonomic history, taxonomic values of morphological characters, species and distribution, infra-genera taxonomic system and the taxonomic research of Chinese Epimedium. For instance, we recognized Epimedium wushanense and clarified that the species, as described in Flora Reipublicae Popularis Sinicae and Flora of China, actually includes four Epimedium species similar in leaflet shape. In general, it was recognized here that Epimedium comprises 62 species, of which 52 species are distributed in China. For Chinese Epimedium species with the most taxonomic problems, the taxonomic research on the taxa was reviewed and the newest species key was proposed along with proposals for those taxonomic problems needing further resolution. This review is of great implication for the identification, exploration and utilization of Epimedii Herba.
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Objective:To determine the molecular characteristics of Streptococcus suis type 2 (SS2) in Zhejiang Province. Methods:Twenty-nine SS2 sporadic human isolates in Zhejiang Province from Januery 2005 to July 2021 were genotyped by pulsed-field gel electrophoresis (PFGE), multilocus sequence typing (MLST), and minimum core genome (MCG) sequence typing.Results:Among 29 strains, 10 PFGE patterns and three main clusters were obtained by PFGE. Twenty-one (72.41%) of the strains were divided into two main branch groups and the remaining eight (27.59%) showed genetic diversity with the similarity ranging from 49.7% to 94.7%. Three sequence types were obtained from 29 strains by MLST, including ST7 (86.21%(25/29)), ST1 (10.34%(3/29)) and ST25 (3.45%(1/29)). In addition, three genotypes were obtained from 29 strains by MCG, including genotype E (41.38%(12/29)), genotype group 1 (55.17%(16/29)) and genotype group 4 (3.45%(1/29)).Conclusions:Two large clonal groups of highly pathogenic strains of SS2 have been prevalent in Zhejiang Province. A few strains display genetic diversity, indicating genetic variation may exist during transmission.
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Emergence of variants of concern (VOC) with altered antigenic structures and waning humoral immunity to SARS-CoV-2 are harbingers of a long pandemic. Administration of a third dose of an inactivated virus vaccine can boost the immune response. Here, we have dissected the immunogenic profiles of antibodies from 3-dose vaccinees, 2-dose vaccinees and convalescents. Better neutralization breadth to VOCs, expeditious recall and long-lasting humoral response bolster 3-dose vaccinees in warding off COVID-19. Analysis of 171 complex structures of SARS-CoV-2 neutralizing antibodies identified structure-activity correlates, revealing ultrapotent, VOCs-resistant and broad-spectrum antigenic patches. Construction of immunogenic and mutational heat maps revealed a direct relationship between "hot" immunogenic sites and areas with high mutation frequencies. Ongoing antibody somatic mutation, memory B cell clonal turnover and antibody composition changes in B cell repertoire driven by prolonged and repeated antigen stimulation confer development of monoclonal antibodies with enhanced neutralizing potency and breadth. Our findings rationalize the use of 3-dose immunization regimens for inactivated vaccines. One sentence summaryA third booster dose of inactivated vaccine produces a highly sifted humoral immune response via a sustained evolution of antibodies capable of effectively neutralizing SARS-CoV-2 variants of concern.
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COVID-19 is a huge threat to global health. Due to the lack of definitive etiological therapeutics currently, effective disease monitoring is of high clinical value for better healthcare and management of the large number of COVID-19 patients. In this study, we recruited 37 COVID-19 patients, collected 176 blood samples upon diagnosis and during treatment, and analyzed cell-free DNA (cfDNA) in these samples. We report gross abnormalities in cfDNA of COVID-19 patients, including elevated GC content, altered molecule size and end motif patterns. More importantly, such cfDNA characteristics reflect patient-specific physiological conditions during treatment. Further analysis on tissue origin tracing of cfDNA reveals frequent tissue injuries in COVID-19 patients, which is supported by clinical diagnoses. Hence, we demonstrate the translational merit of cfDNA as valuable analyte for effective disease monitoring, as well as tissue injury assessment in COVID-19 patients.
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Fibroblast growth factor 19 (FGF19) is an endocrine hormone and it's primarily regulated by bile acids. FGF19 helps to reduce body weight, a variety of weight loss mechanism are achieved by increasing the level of FGF19. FGF19 can reverse mitochondrial dysfunction caused by obesity. The main pathogenesis of diabetes is insulin resistance and islet β cell defects, which can cause microangiopathy and cardiovascular diseases. FGF19 can fundamentally protect the function of islet β cells, improve insulin resistance, increase insulin sensitivity, and achieve the purpose of reducing blood glucose by insulin-independent manner. Diabetic patients have different degrees of complications. FGF19 can protect the diabetic cardiomyocytes by improving the energy metabolism of diabetic cardiomyocytes. It may play a protective role in the development of diabetic retinopathy and diabetic nephropathy. The results of this review paper show that FGF19 plays an important role in the treatment of obesity, diabetes and its complications, and regulating FGF19 is expected to become a new strategy for the treatment of obesity and diabetes.