Objective: To evaluate the efficacy and safety of Nocardia rubra cell wall skeleton (Nr-CWS) in the treatment of persistent cervical high-risk human papillomavirus (HR-HPV) infection. Methods: A randomized, double blind, multi-center trial was conducted. A total of 688 patients with clinically and pathologically confirmed HR-HPV infection of the cervix diagnosed in 13 hispital nationwide were recruited and divided into: (1) patients with simple HR-HPV infection lasting for 12 months or more; (2) patients with cervical intraepithelial neoplasia (CIN) Ⅰ and HR-HPV infection lasting for 12 months or more; (3) patients with the same HR-HPV subtype with no CINⅡ and more lesions after treatment with CINⅡ or CIN Ⅲ (CINⅡ/CIN Ⅲ). All participants were randomly divided into the test group and the control group at a ratio of 2∶1. The test group was locally treated with Nr-CWS freeze-dried powder and the control group was treated with freeze-dried powder without Nr-CWS. The efficacy and negative conversion rate of various subtypes of HR-HPV were evaluated at 1, 4, 8, and 12 months after treatment. The safety indicators of initial diagnosis and treatment were observed. Results: (1) This study included 555 patients with HR-HPV infection in the cervix (included 368 in the test group and 187 in the control group), with an age of (44.1±10.0) years. The baseline characteristics of the two groups of subjects, including age, proportion of Han people, weight, composition of HR-HPV subtypes, and proportion of each subgroup, were compared with no statistically significant differences (all P>0.05). (2) After 12 months of treatment, the effective rates of the test group and the control group were 91.0% (335/368) and 44.9% (84/187), respectively. The difference between the two groups was statistically significant (χ²=142.520, P<0.001). After 12 months of treatment, the negative conversion rates of HPV 16, 18, 52, and 58 infection in the test group were 79.2% (84/106), 73.3% (22/30), 83.1% (54/65), and 77.4% (48/62), respectively. The control group were 21.6% (11/51), 1/9, 35.1% (13/37), and 20.0% (8/40), respectively. The differences between the two groups were statistically significant (all P<0.001). (3) There were no statistically significant differences in vital signs (body weight, body temperature, respiration, pulse rate, systolic blood pressure, diastolic blood pressure, etc.) and laboratory routine indicators (blood cell analysis, urine routine examination) between the test group and the control group before treatment and at 1, 4, 8, and 12 months after treatment (all P>0.05); there was no statistically significant difference in the incidence of adverse reactions related to the investigational drug between the two groups of subjects [8.7% (32/368) vs 8.0% (15/187), respectively; χ²=0.073, P=0.787]. Conclusion: External use of Nr-CWS has good efficacy and safety in the treatment of high-risk HPV persistent infection in the cervix.
Female ; Humans ; Adult ; Middle Aged ; Cervix Uteri/pathology* ; Uterine Cervical Neoplasms/pathology* ; Papillomavirus Infections/diagnosis* ; Cell Wall Skeleton ; Persistent Infection ; Powders ; Uterine Cervical Dysplasia/pathology* ; Immunotherapy ; Papillomaviridae

Humans ; Squamous Cell Carcinoma of Head and Neck ; RNA, Messenger ; Immunohistochemistry ; Papillomavirus Infections/diagnosis* ; Oncogene Proteins, Viral/genetics* ; Head and Neck Neoplasms ; Cyclin-Dependent Kinase Inhibitor p16 ; Papillomaviridae ; Papillomavirus E7 Proteins/genetics* ; DNA, Viral

Objective: To analyze the epidemiology and spatial-temporal distribution characteristics of hand, foot and mouth disease (HFMD) in Shanxi province. Methods: The data of HFMD in Shanxi province from 2009 to 2020 were collected from notifiable disease management information system of Chinese information system for disease control and prevention and analyzed by descriptive epidemiology, Joinpoint regression, spatial autocorrelation analysis and spatio- temporal scanning analysis. Results: A total of 293 477 HFMD cases were reported in Shanxi province from 2009 to 2020, with an average annual incidence of 67.64/100 000 (293 477/433 867 454), severe disease rate of 5.36/100 000 (2 326/433 867 454), severe disease ratio of 0.79%(2 326/293 477), mortality of 0.015/100 000 (66/433 867 454), and fatality rate of 22.49/100 000 (66/293 477). The reported incidence rate, severe disease rate, mortality rate and fatality rate of HFMD showed decreasing trends. The main high-risk groups were scattered children and kindergarten children aged 0-5. The incidence of HFMD had obvious seasonal variation, with two peaks every year: the main peak was during June-July, the secondary peak was during September-October and the peak period is from April to November. A total of 13 942 laboratory cases were confirmed, with a diagnosis rate of 4.75% (13 942/293 477), including 4 438 (35.11%, 4 438/293 477) Enterovirus A71 (EV-A71) positive cases, 4 609 (33.06%, 4 609/293 477) Coxsackievirus A16 (CV-A16) positive cases, and 4 895 (31.83%, 4 895/293 477) other enterovirus positive cases. There was a spatial positive correlation (Moran's I ranged from 0.12 to 0.58, all P<0.05) and the spatial clustering was obvious. High-risk regions were mainly distributed in Taiyuan in central Shanxi province, Linfen and Yuncheng in southern Shanxi province, and Changzhi in southeastern Shanxi province. Spatial-temporal scanning analysis revealed 1 the most likely cluster and 8 secondary likely clusters, of which the most likely cluster (RR=2.65, LLR=22 387.42, P<0.001) located in Taiyuan and Jinzhong city, Shanxi province, including 12 counties (districts), and accumulated from April 1, 2009 to November 30, 2018. Conclusions: There was obvious spatial-temporal clustering of HFMD in Shanxi province, and the epidemic situation was in decline. The key areas were the districts in urban areas and the counties adjacent to it. Meanwhile, the monitoring and classification of other enterovirus types of HFMD should be strengthened.
Child ; Humans ; Hand, Foot and Mouth Disease/epidemiology* ; Spatial Analysis ; Enterovirus Infections ; Spatio-Temporal Analysis ; Cluster Analysis

Biosimilars are biological medicinal products that are highly similar to an already licensed reference product in terms of quality, safety, and efficacy. BAT1706 is being developed by Bio-Thera Solutions, Ltd. as a proposed biosimilar candidate to bevacizumab reference product (Avastin^®). Bevacizumab acts by specifically binding to vascular endothelial growth factor A (VEGF-A), and preventing the interaction of VEGF-A with its receptors on the surface of endothelial cells, then blocking the downstream signaling pathway mediated by ligand-receptor, and inhibiting endothelial angiogenesis, thus inhibiting tumor growth. Comprehensive analytical characterization studies incorporating orthogonal analytical techniques were performed to compare the in vitro functional activities of BAT1706 and Avastin^®. BAT1706 and Avastin^® showed highly similar binding activity to multiple VEGF-A isoforms and equivalent VEGF-A neutralizing activity, as well as inhibitory activity of VEGF receptor (VEGFR)-2 tyrosine kinase autophosphorylation. Both products exhibited similar binding of the Fcγ receptors and a lack of Fc-related effector functions such as antibody-dependent cell-mediated cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC). Overall, the results demonstrate that BAT1706 and Avastin^® are highly similar in terms of in vitro functional activities.

This study was to investigate the protective effect of paeoniflorin (PF) on hydrogen peroxide-induced injury. Firstly, "SMILES" of PF was searched in Pubchem and further was used for reverse molecular docking in Swiss Target Prediction database to obtain potential targets. Injury-related molecules were obtained from GeenCards database, and the predicted targets of PF for injury treatment were selected by Wayne diagram. For mechanism analysis, the protein-protein interactions were constructed by String, and the KEGG analysis was conducted in Webgestalt. Then, cell viability and cytotoxicity assay were established by CCK8 assay. Also, the experimental cells were allocated to control, model (200 μmol·L

Small proteins specifically refer to proteins consisting of less than 100 amino acids translated from small open reading frames (sORFs), which were usually missed in previous genome annotation. The significance of small proteins has been revealed in current years, along with the discovery of their diverse functions. However, systematic annotation of small proteins is still insufficient. SmProt was specially developed to provide valuable information on small proteins for scientific community. Here we present the update of SmProt, which emphasizes reliability of translated sORFs, genetic variants in translated sORFs, disease-specific sORF translation events or sequences, and remarkably increased data volume. More components such as non-ATG translation initiation, function, and new sources are also included. SmProt incorporated 638,958 unique small proteins curated from 3,165,229 primary records, which were computationally predicted from 419 ribosome profiling (Ribo-seq) datasets or collected from literature and other sources from 370 cell lines or tissues in 8 species (Homo sapiens, Mus musculus, Rattus norvegicus, Drosophila melanogaster, Danio rerio, Saccharomyces cere-visiae, Caenorhabditis elegans, and Escherichia coli). In addition, small protein families identified from human micro-biomes were also collected. All datasets in SmProt are free to access, and available for browse, search, and bulk downloads at http://bigdata.ibp.ac.cn/SmProt/.

In this paper, through the collection and collation of ancient herbs, medical books and prescriptions, combined with modern literature, the historical changes of the name, origin, position, medicinal parts, collection, processing and processing of bluegrass were systematically combed and verified.It can be seen from the research that bluegrass was first used as medicine by the fruit, namely blueberry, which was originally Polygonum tinctorium. Since the Ming and Qing Dynasties, blueberry was rarely used, and it has been no longer used medicinally. In the Wei and Jin Dynasties, the medicinal parts extended to the stems and leaves, and most of them used juice as medicine.Since the Tang Dynasty, origin has been extended to Isatis indigotica, Baphicacanthus cusia, Indigofera tinctoria, Compositae plant Wulan, etc. In the Song Dynasty, the medicinal parts extended to the roots, and the "Banlangen" began to appear, and gradually became the main medicinal parts of blue medicinal materials, the main base of which was B. cusia. Since the Qing Dynasty, I. indigotica, a Cruciferae, has gradually become a genuine indigo root, while B. cusia has become a southern indigo root. It was the first mineral dye imported from abroad for thrush, and then used as medicine, also known as clam powder. Because it was found that it had the same effect with the extract of bluegrass, it was also named indigo naturalis in China, which has lasted till now. The main stream of Isatidis Folium in the past dynasties is the dry stem and leaf of Clerodendrum cyrtophylum. Since the Qing Dynasty, the stem and leaf of Isatis indigotica, P. tinctorium and other blue grasses have been gradually mixed as substitutes and gradually become the mainstream.
China ; Clerodendrum ; Isatis ; Medicine, Chinese Traditional ; Plants, Medicinal

3-Hydroxy-3-methylglutaryl coenzyme A reductase (HMGR) is the first rate-limiting enzyme of terpenoid biosynthesis in the mevalonic acid pathway (MVA) pathway. It is an important regulatory site in terpenoids metabolism pathway in the cytoplasm. According to the transcriptome database of Cinnamomum camphora, two HMGRs named CcHMGR1 (GenBank: MN163055) and CcHMGR2 (GenBank: MN163056) were cloned by cDNA from C. camphora. The ORF of CcHMGR1 and CcHMGR2 is composed of 1 689 bp and 1 683 bp, respectively, encoding 562 and 560 amino acids. The bioinformatics analysis of CcHMGR1 and CcHMGR2 indicated that the molecular weight of the encoded protein is 59.819 kDa and 59.397 kDa, with a theoretically isoelectric point of 8.20 and 8.61, respectively. There are 2 transmembrane structures without signal peptide existing in the encoded amino acid of CcHMGRs. The analysis of sequence alignment and phylogenetic tree showed that theCcHMGRs belonged to the HMGR family. The camphor is divided into five chemitypes, according to the main chemical compoundsin C. camphora. The results of the real time PCR indicated that the expression level of CcHMGRs in Cineol type was higher than that in Linalool type, iso-nerolidol type, Camphor type and Borneol type. CcHMGRs expressed highest in roots and lowest in branches. In this study, the cDNA full length of CcHMGRs were cloned from C. camphora for the first time. Our results revealed that the expression level of CcHMGRs were different among five chemical types and different plant tissues, and the research provides foundation for further study of the terpenoids biosynthetic pathway in C. camphora.

To study the clinical effect of oral sirolimus in the treatment of children with blue rubber bleb nevus syndrome (BRBNS) in the gastrointestinal tract, a retrospective analysis was performed on the clinical data and follow-up results of two children with BRBNS treated by sirolimus. The two children with BRBNS had gastrointestinal bleeding and anemia and were treated with sirolimus at a dose of 1 mg/day as part of treatment. The plasma concentration of the drug was maintained between 2.5-12.0 ng/mL. The children showed disappearance of gastrointestinal bleeding and improvements in anemia and coagulation function, and blood transfusion could be stopped during treatment, with no obvious adverse drug reactions. PubMed, Wanfang Data, and CNKI were searched for related articles on sirolimus in the treatment of BRBNS. A total of 26 cases of children with BRBNS, aged 0-18 years, were obtained. With the addition of the 2 cases in this study, sirolimus treatment achieved a satisfactory clinical effect in all 28 cases. Sirolimus may be effective and safe in the treatment of children with BRBNS, and further prospective studies are needed to evaluate the long-term efficacy of this drug.
Adolescent ; Child ; Child, Preschool ; Gastrointestinal Neoplasms ; drug therapy ; Humans ; Infant ; Infant, Newborn ; Nevus, Blue ; drug therapy ; Prospective Studies ; Retrospective Studies ; Sirolimus ; therapeutic use ; Skin Neoplasms ; drug therapy

Development of rapid analytical methods and establishment of toxic component limitation standards are of great importance in quality control of traditional Chinese medicine. Herein, an on-line extraction electrospray ionization mass spectrometry (oEESI-MS) coupled with a novel whole process integral quantification strategy was developed and applied to direct determination of nine key aconitine-type alkaloids in 20 proprietary Chinese medicines (APCMs). Multi-type dosage forms (, tablets, capsules, pills, granules, and liquid preparation) of APCM could be determined directly with excellent versatility. The strategy has the characteristics of high throughput, good tolerance of matrix interference, small amount of sample (∼0.5 mg) and reagent (∼240 μL) consumption, and short analysis time for single sample (<15 min). The results were proved to be credible by high performance liquid chromatography-mass spectrometry (LC-MS) and electrospray ionization mass spectrometry, respectively. Moreover, the limitation standard for the toxic aconitines in 20 APCMs was established based on the holistic weight toxicity (HWT) evaluation and the severally, and turned out that HWT-based toxicity evaluation results were closer to the real clinical applications. Hence, a more accurate and reliable APCM toxicity limitation was established and expected to play an important guiding role in clinics. The current study extended the power of ambient MS as a method for the direct quantification of molecules in complex samples, which is commonly required in pharmaceutical analysis, food safety control, public security, and many other disciplines.