Circular RNAs (circRNAs) are a kind of non-coding RNA (ncRNA) with covalent closed-loop structure. They have attracted more and more attention because of their high stability, evolutionary conservatism, and tissue expression specificity. It has shown that circRNAs are involved in the development of a variety of diseases including malignant tumors recently. Nasopharyngeal carcinoma (NPC) is a malignant tumor that occurs in the nasopharynx and has a unique ethnic and geographical distribution in South China and Southeast Asia. Epstein-Barr virus (EBV) infection is closely related to the development of NPC. Radiotherapy and chemotherapy are the mainstays of treatment for NPC. But tumor recurrence or distant metastasis is the leading cause of death in patients with NPC. Several studies have shown that circRNAs, as gene expression regulators, play an important role in NPC and affect the progression of NPC. This review mainly summarized the research status of abnormally expressed circRNAs in NPC and EBV-encoded circRNAs. We also discussed the possibility of circRNAs as a therapeutic target, diagnostic and prognostic marker for NPC.

The concept of'harmony'is the soul of traditional Chinese culture,which has a profound impact on the formation and development of traditional Chinese medicine(TCM).TCM is rooted in traditional Chinese culture,and the mode of thinking in TCM is in line with traditional Chinese culture.Based on the harmony culture,TCM has developed a unique view of health,disease and therapeutics.From the view of the harmony culture and by combining with years of clinical experience in treating dermatosis,Chinese medical master XUAN Guo-Wei has applied the concept of'harmony'in the TCM syndrome differentiation and treatment system in clinic,and has developed the academic thoughts of harmonizing therapy for removing toxins for the diagnosis and treatment of dermatosis.The thoughts of harmonizing therapy for removing toxins includes four aspects,namely harmonizing yin and yang,harmonizing healthy qi and pathogenic qi,harmonizing water and fire(i.e.,clod and hot),and harmonizing the administration of formula and drugs,aiming to remove toxins and expel pathogens and value the harmony.The thoughts of harmonizing therapy for removing toxins will beneficial to the comprehensive understanding of the unique health-disease-therapeutics concept in TCM,and will be helpful for managing the doctor-patient relationship,which is of enlightening significance to the modern clinical practice with TCM.

Humans ; Phosphorylation ; Serine ; Protein Serine-Threonine Kinases/metabolism* ; Spasms, Infantile

Objective: To construct a virtual reconstruction method including midspan maxillary defects and provide clinical reference by training a generative adversarial network (GAN) model. Methods: The CT data of middle-aged Han patients with oral diseases who visited the Department of Radiology, West China Hospital of Stomatology, Sichuan University from June 2015 to June 2022 were collected, where the CT data of 100 healthy maxilla and 15 maxillary defects (5 simple unilateral defects, 5 unilateral defects involving zygomatic bone, 5 midspan defects) were selected. Mimics was used to create spherical phantom and simulate bone defects around the healthy maxillas, including simple unilateral defects, unilateral defects involving zygomatic bone and midspan defects. The original image was set as the correct reference for the reconstruction: artificial defects paired with the correct reference were divided into training set (n=70), validation set (n=20) and test set (n=10), where the first two were used to train the GAN model, and the test set was used to evaluate the GAN performance. Data from 15 clinical defects were imported into the trained GAN model for reconstruction, with mirroring and GAN-based virtual reconstruction for unilateral clinical defects, and only the latter method was adopted for midspan defects. The reconstruction results were divided into mirror reconstruction group (n=10), unilateral defect GAN reconstruction group (n=10) and midspan defect GAN reconstruction group (n=5). The test set, mirror reconstruction group, and unilateral defect GAN reconstruction group were quantitatively evaluated, whose quantitative indicators were Dice similarity coefficient (DSC) and 95% Hausdorff distance (HD95), and the group results were subjected to one-way ANOVA and Tukey test. The test set, mirror reconstruction group, unilateral defect GAN reconstruction group and midspan defect GAN reconstruction group were qualitatively scored, and Kruskal-Wallis test and Bonferroni correction were used for the total score of each group. Results: The total differences in the test set, mirror reconstruction group, unilateral defect GAN reconstruction group DCS (0.891±0.049, 0.721±0.047, 0.778±0.057, respectively) and HD95 [(3.58±1.51), (5.19±1.38), (4.51±1.10) mm, respectively] were statistically significant (F=28.08, P<0.001; F=3.62, P=0.041); among them, the test set DSC was significantly larger than the mirror reconstruction group (P<0.05), and the test set HD95 was significantly less than the mirror reconstruction group (P<0.05). Overall difference in qualitative total scores [8 (1), 6 (2), 6 (2), and 4 (2) points, respectively] in the test set, mirror reconstruction group, unilateral defect GAN reconstruction group, and midspan defect GAN reconstruction group were statistical significance (H=18.13, P<0.001); pairwise comparison showed that the total score of the test set was significantly higher than that of the mirror reconstruction group (P<0.05). Conclusions: The virtual reconstruction method based on GAN proposed in this study has better virtual reconstruction effect of unilateral defect than mirror technique, and can also realize virtual reconstruction of maxillary midspan defect.
Humans ; Middle Aged ; Maxilla/surgery* ; Deep Learning ; China

Objective:To explore the value of 5G-based robotic remote ultrasound diagnosis system in musculoskeletal joint injuries.Methods:From March to December 2020, 58 volunteers at a training base who felt musculoskeletal pain or paresthesia were selected and performed both robotic remote ultrasound (remote ultrasound group) and conventional ultrasound (portable ultrasound group). The two types of examinations were compared, the consistency of the two diagnosis results was analyzed by the Kappa test, and the the difference of the diagnosis results was compared by McNemar test.Results:Among the 58 volunteers, 40 cases were positive by both methods and 11 volunteers had 2-3 positive results. There were 59 positive results in the remote ultrasound group and 64 positive results in the portable ultrasound group. The positive rate of the examination sites from high to low was knee joint>foot and ankle joint >hand and wrist joint >shoulder joint>elbow joint, calf and hip. The diagnosis results of the two groups were in good consistency (Kappa=0.782, P<0.001), and there was no statistically significant difference in the diagnosis results between the two groups (χ 2=3.2, P=0.063). Five more diseases with positive results were detected in the portable ultrasound group: 1 meniscus injury, 1 medial collateral ligament injury, 1 soft tissue injury around the metatarsal, 1 biceps tendinitis with effusion and 1 cubital ulnar nerve subluxation. Conclusions:The 5G-based robotic remote ultrasound system has good consistency with conventional ultrasound in the diagnosis of musculoskeletal injures. It can be applied to the ultrasound diagnosis of musculoskeletal joint injuries in remote areas.

OBJECTIVE: To express and purify the antigenic peptide of adeno-associated virus (AAV) capsid conserved regions in prokaryotic cells and prepare its rabbit polyclonal antibody. METHODS: The DNA sequence encoding the conserved regions of AAV capsid protein was synthesized and cloned into the vector pET30a to obtain the plasmid pET30a-AAV-CR for prokaryotic expression and purification of the conserved peptides. Coomassie blue staining and Western blotting were used to identify the AAV conserved peptides. Japanese big ear white rabbits were immunized with AAV conserved region protein to prepare polyclonal antibody, with the rabbits injected with PBS as the control group. The antibody titer was determined with ELISA, and the performance of the antibody for recognizing capsid protein sequences of AAV1-AAV10 was assessed with Western blotting and immunofluorescence assay. RESULTS: The plasmid pET30a-AAV-CR was successfully constructed, and a recombinant protein with a relative molecular mass of 17000 was obtained. The purified protein induced the production of antibodies against the conserved regions of AAV capsid in rabbits, and the titer of the purified antibodies reached 1:320 000. The antibodies were capable of recognizing a wide range of capsid protein sequences of AAV1-AAV10. CONCLUSION We successfully obtained the polyclonal antibodies against AAV capsid conserved region protein from rabbits, which facilitate future studies of AAV vector development and the biological functions of AAV.
Animals ; Antibodies ; Capsid ; Capsid Proteins/genetics* ; Dependovirus/genetics* ; Prokaryotic Cells ; Rabbits ; Recombinant Proteins/genetics*

OBJECTIVE: To investigate the effect and mechanism of artesunate (ARTS) combined with cytarabine(Ara-C) and/or daunorubicin (DNR) on the proliferation and apoptosis of MV4-11 human mixed-lineage leukemia rearranged（MLL-r） acute myeloid leukemia (AML) cell line. METHODS: CCK-8 assay was used to detect the proliferation effect of individual or in combination of ARTS, DNR, Ara-C on MV4-11 cells. The IC₅₀ of ARTS, DNR and Ara-C was calculated separately. The cell apoptosis and expression of receptors DR4 and DR5 were detected by flow cytometry. Western blot was used to detect the expression of Caspase-3 and Caspase-9 in each groups. RESULTS: The inhibition effect of ARTS, Ara-C and DNR on the proliferation of MV4-11 were all dose-dependently (r=0.99, 0.90 and 0.97, respectively). The IC₅₀ of ARTS, Ara-C and DNR on MV4-11 for 48 hours were 0.31 μg/ml, 1.43 μmol/L and 22.47 nmol/L, respectively. At the dose of ARTS 0.3 μg/ml， Ara-C 1.0 μmol/L and DNR 15 nmol/L, the proliferation rate for 48 hours of the tri-combination treatment was significantly lower than that of the bi-combination treatment, while both were significantly lower than that of the individual treatment (all P＜0.05). In terms of bi-combination treatment, the cells proliferation rate for 48 hours of the ARTS+Ara-C group was significantly lower than that of the ARTS+DNR group, while both were significantly lower than that of the Ara-C+DNR group (all P＜0.05). The cooperativity index (CI) of bi- and tri-combination treatment were all less than 1. After 48 hours of drug action, the cell apoptosis rate of the ARTS+DNR+Ara-C group was significantly higher than that of the Ara-C+DNR group, while both were significantly higher than that of the ARTS+DNR group (all P＜0.05). Meanwhile, the was no statistical difference between the cells apoptotic rate of the ARTS+DNR+Ara-C group and the ARTS+Ara-C group (P>0.05). The expression of DR4 and DR5 also showed no difference between control group and drug group. Compared with the DNR+Ara-C group, the expressions of Caspase-3 were significantly down-regulated in both the ARTS+DNR+Ara-C group and the ARTS+Ara-C group (all P＜0.05). The down-regulation of Caspase-3 expression was the most significantly in the combination group of three drugs, while the Caspase-9 expressions in different groups showed no apparent change. CONCLUSION The in vitro study showed that tri-combination of ARTS+Ara-C+DNR and bi-combination of ARTS+Ara-C could inhibit the proliferation and promote apoptosis of MV4-11 cell line. The inhibition effect of these two combinations were significantly superior to that of the traditional Ara-C+DNR treatment. The mechanism underlying this finding may be identified by the down regulation of Caspase-3, while no altered expression was observed of Caspase-9, DR4 and DR5.
Humans ; Cytarabine/pharmacology* ; Daunorubicin/pharmacology* ; Caspase 3 ; Caspase 9 ; Artesunate/pharmacology* ; Leukemia, Myeloid, Acute ; Apoptosis ; Cell Line

Objective:To analyze the compatibility rules of prescriptions containing Forsythiae Fructus based on data mining and explore the anti-inflammatory mechanism of Forsythiae Fructus based on network pharmacology，so as to provide reference for the rational clinical application of Forsythiae Fructus and the development of health foods and new Chinese medicines. Method:The prescriptions containing Forsythiae Fructus in the Dictionary of Traditional Chinese Medicine Prescriptions were collected，based on which a clinical prescription database was constructed. The Chinese herbs combined with Forsythiae Fructus and the corresponding indications were subjected to frequency statistics，association rule analysis，and complex network analysis using SPSS Statistics 26，IBM SPSS Modeler 18.0，and Gephi 9.2. The active components and targets of Forsythiae Fructus for anti-inflammation were retrieved from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform （TCMSP），BATMAN-TCM，and SEA，and the targets related to anti-inflammation from GeneCards，Online Mendelian Inheritance in Man （OMIM），CTD，and GenCLiP3. Following the analysis of protein-protein interactions （PPI） with STRING，a PPI network was constructed. The enrichment analysis was performed using Metascape，and the active component-anti-inflammation target-signaling pathway network of Forsythiae Fructus was constructed by Cytoscape 3.8.2. Result:According to the inclusion and exclusion criteria，2 245 prescriptions containing Forsythiae Fructus were harvested，involving 512 Chinese herbs，with a total usage frequency of 27 314. The Chinese herbs that were most frequently combined with Forsythiae Fructus （>800 times） were Glycyrrhizae Radix et Rhizoma （1 483 times），Scutellariae Radix （964 times），and Angelicae Sinensis Radix （842 times）. Hence，the herbal pairs "Forsythiae Fructus-Scutellariae Radix" and "Forsythiae Fructus-Angelicae Sinensis Radix" were further explored. The prescriptions containing Forsythiae Fructus could be utilized for the treatment of 29 kinds of diseases，and three representative disease categories including "carbuncle，gangrene，sores and ulcers"，"ophthalmic diseases and syndromes" and "epidemic diseases" are selected for data mining. There were 19 association rules obtained with "Forsythiae Fructus-Glycyrrhizae Radix et Rhizoma-Lonicerae Japonicae Flos-Angelicae Sinensis Radix" as the core herb combination for "carbuncle，gangrene，sores and ulcers". The clustering analysis revealed one multi-herb clustering group，four herbal pairs，and single herb Lonicerae Japonicae Flos，the complex network analysis four herbal modules，and the factor analysis six common factors. There were 23 association rules obtained with "Forsythiae Fructus-Glycyrrhizae Radix et Rhizoma-Scutellariae Radix-Angelicae Sinensis Radix" as the core herb combination for "ophthalmic diseases and syndromes". The clustering analysis revealed two multi-herb clustering groups and four herbal pairs，the complex network analysis four herbal modules，and the factor analysis five common factors. There were 28 association rules obtained with "Forsythiae Fructus-Glycyrrhizae Radix et Rhizoma-Menthae Haplocalycis Herba-Lonicerae Japonicae Flos" as the core herb combination for "epidemic diseases". The clustering analysis revealed three multi-herb clustering groups，one herbal pair，and two single herbs Forsythiae Fructus and Glycyrrhizae Radix et Rhizoma，the complex network analysis four herbal modules，and the factor analysis five common factors. As demonstrated by network pharmacology-based analysis，the core anti-inflammation components of Forsythiae Fructus were quercetin，luteolin，and kaempferol，and the core targets were phosphoinositide-3-kinase regulatory subunit 1 （PIK3R1），protein kinase B 1 （Akt1），and epidermal growth factor receptor（EGFR）. The biological pathways were mainly concentrated in proteoglycans in cancer，pathways in cancer，and PI3K/Akt signaling pathway，with such functions as inhibition of transcription factors，regulation of enzyme activity，and inflammation-related gene expression involved. Conclusion:This study employed a variety of data mining techniques to objectively，intuitively，and scientifically uncover the compatibility rules of Forsythiae Fructus in the treatment of high-frequency diseases. It has been found that Forsythiae Fructus is often combined with heat-clearing herbs，tonifying herbs，exterior-releasing herbs，and blood-activating and stasis-resolving herbs for diverse diseases and syndromes. Under the premise of clearing heat and removing toxin，reinforcing healthy Qi and dredging stagnation are also emphasized. According to the degree of internal heat exuberance，the heat-clearing herbs with different merits are combined. This study has revealed the unique advantages of Forsythiae Fructus in the treatment of specific diseases and syndromes as well as its multi-component，multi-target，and multi-pathway mechanisms in anti-inflammation，breaking through the limitations in modern clinical and experimental research of Forsythiae Fructus. These findings are of great significance for guiding the rational clinical application of Forsythiae Fructus and the development of health foods and new Chinese medicines，thus better accelerating the development of Chinese medicine health industry.

Objective:To explore the related factors of epilepsy secondary to aneurysmal subarachnoid hemorrhage in the elderly.Methods:From January 2015 to January 2019, 213 elderly patients with aneurysmal subarachnoid hemorrhage admitted to Wuhan Hospital of Traditional Chinese Medicine were divided into epilepsy group(46 cases) and non-epilepsy group(167 cases) according to whether secondary epilepsy.Univariate analysis was used to analyze the related factors affecting epilepsy secondary to aneurysmal subarachnoid hemorrhage in the elderly, and multivariate logistic regression was used to analyze the risk factors of epilepsy secondary to aneurysmal subarachnoid hemorrhage in the elderly.The investigation factors included sex, age, hypertension, diabetes mellitus, smoking history, location of responsible aneurysms, number of aneurysms, intracranial hematoma, hydrocephalus and neurological sequelae.Results:Univariate analysis showed that there were no statistically significant differences in sex, age, history of diabetes mellitus and smoking between the two groups(all P>0.05). There were statistically significant differences between the epilepsy group and non epilepsy group in hypertension(15 cases vs.22 cases), location of responsible aneurysms in middle cerebral artery(22 cases vs.24 cases), number of aneurysms(23 cases vs.41 cases), intracranial hematoma(15 cases vs.26 cases), hydrocephalus(15 cases vs.21 cases) and neurological sequelae(14 cases vs.20 cases)(χ 2=9.491, 23.840, 11.113, 6.737, 10.306, 9.161, all P<0.05). The results of multivariate analysis showed that hypertension, middle cerebral artery, multiple aneurysms, intracranial hematoma, hydrocephalus and neurologic sequelae were risk factors for epilepsy secondary to aneurysmal subarachnoid hemorrhage in the elderly[ OR(95% CI)2.361(1.476-3.421), 3.012(1.935-1.845), 1.494(1.027-1.845), 2.785(1.684-3.982), 1.920(1.283-2.984), 1.637(1.171-2.316)]. Conclusion:There are many factors influencing secondary epilepsy in elderly patients with aneurysmal subarachnoid hemorrhage.In order to reduce the incidence of secondary epilepsy, preventive measures should be taken against the above risk factors.

OBJECTIVE: To compare the clinical pregnancy rates between two types of endometrial preparation protocolsnatural cycle（NC）and hormone replacement cycle（HRT）-in patients with thin endometrium in the frozen-thawed embryo transfer（FET）cycles.METHODS: From January 2012 to December 2018,FET patients with endometrial thickness ≤7 mm on the day of human chorionic gonadotropin（h CG）trigger in Reproductive Medicine Center of the First Affiliated Hospital of Sun Yat-sen University were selected as research subjects.According to the endometrial preparation protocols,they were divided into NC group and HRT group.Totally 117 pairs were successfully matched using the propensity score matching method.The matching variables were age,embryo type and number of transferred embryos,and the embryo implantation rate and clinical pregnancy rate of the two matched groups were compared.RESULTS: There was no significant difference in embryo implantation rate（36.47% vs. 39.03%）or clinical pregnancy rate（44.40% vs. 52.10%）between NC group and HRT group（P> 0.05）.CONCLUSION: NC group and HRT group had similar pregnancy rate in patients with thin endometrium in FET cycles.Individualized protocols can be adopted according to the characteristics of patients with thin endometrium.