Objective: To investigate the efficacy and safety of ⁹⁹Technetium-methylenediphosphonate injection (⁹⁹Tc-MDP) in the treatment of thyroid associated ophthalmopathy (TAO). Methods: The trail was conducted in Affiliated Zhongshan Hospital of Dalian University. Patients were recruited from October 2016 to October 2018. Fifty patients with active moderate to severe TAO were randomly assigned to receive ⁹⁹Tc-MDP (n = 25) or methylprednisolone administered intravenously (n = 25), the final completion of treatment and follow-up were 21 and 20 cases, respectively. In ⁹⁹Tc-MDP group, 30 sets of ⁹⁹Tc-MDP were applied to each course of treatment for 10 d, with a course interval of 20 d, a total of 3 courses of treatment. Patients in methylprednisolone group were given a pulse regimen, once every week for a total of 12 infusions, altogether 4.5 g in 12 weeks. The clinical activity score (CAS) and exophthalmos were assessed in a patient at weeks 12 and 24, respectively. A response was defined as a reduction of 2 points or more in CAS and reduction of 2 mm or more in exophthalmos. Safety was assessed according to the incidence of adverse events at week 12. Results: At week 12 treatment, no significant difference was observed in CAS and exophthalmos between the two groups [CAS: (2.48 ± 0.60) , (2.20 ± 0.62) points, exophthalmos: (2.57 ± 1.02), (2.20 ± 1.09) mm, P > 0.05]. Adverse events in ⁹⁹Tc-MDP group was significantly lower than that in methylprednisolone group [4.8%(1/21) vs 40.0%(8/20), P < 0.05]. At week 24, the reduction in the CAS in ⁹⁹Tc-MDP group was significantly greater than that in methylprednisolone group [CAS: (3.86 ± 0.67), (3.05 ± 0.59) points, P < 0.05]. The difference in exophthalmos of patients between the two groups was not statistically significant [(3.17 ± 0.60), (2.88 ± 0.57) mm, P > 0.05]. The difference in total effective rate of patients between the two groups was not statistically significant (P > 0.05). Conclusion ⁹⁹Tc-MDP regimen could provide similar benefit to methylprednisolone pulse therapy for those patients with TAO, but with longer reduction in CAS and less adverse events.

Objective To identify and analyze the genetic characterization of rubella viruses isolated in Chongqing from 2011 to 2016 ,so as to provide molecular epidemiological evidence for rubella prevention and control .Methods Virus samples isolated from Chongqing city from 2011 to 2016 for detection of rubella virus nucleic acid were collected ,and their genotypes were identified by sequence analysis .Phylogenetic tree construction and genetic distance analysis were carried out among rubella virus types ,reference strains and other provinces and cities in GenBank .Results The predominant genotype from 2011 to 2013 was 1E (94/103) ,from 2014 to 2016 was 2B (50/56) .Only one strain of genotype 2A was found in 2014 .The homology of 1E genotype between Chongqing and other provinces was 97 .63% to 99 .73% ,with an average of 98 .90% .The homology of 2B genotype between Chongqing and other provinces was 95 .77% to 99 .73% ,with an average of 98 .30% .The Chongqing rubella viruses strains didn′t isolate form oth-er province strains of China in phylogenetic tree .Conclusion The predominant genotype 1E of rubella virus in Chongqing was grad-ually replaced by 2B in recent years .The rubella virus genotypes in Chongqing are changing ,and the dominant strains are in a state of coevolution with other provinces and cities .

Enteroviruses are currently divided into groups A to J, among which groups A to D can infect human body. People infected with enterovirus can present invisible infection, which can lead to different clinical symptoms when the immunity is weakened. Among the diseases caused by enteroviruses, hand-foot-mouth disease, herpetic angina, and encephalitis have attracted much attention. Coxsackie virus A21 (CV-A21) belongs to enterovirus C group, which mainly causes acute respiratory tract infection. According to research reports, CV-A21 infection has been found in many countries and regions, and the infection scope is gradually expanding. In the past two years, it has been found that CV-A21 infection has a significant association with the outbreak of acute respiratory tract infection. This indicates that acute respiratory tract infection caused by CV-A21 infection may have potential public health problems. However, there are few studies on the epidemiology and pathogenic mechanism of this virus, and most of the studies are on the mechanism of its oncolytic action on specific malignant tumors. Therefore, in this paper, the structural characteristics, epidemiological characteristics, infection mechanism and oncolytic effects of CV-A21 are reviewed to provide relevant clues for the understanding and exploration of CV-A21.

Objective To understand the pathogen composition of viral diarrhea in Chongqing, and to provide reference for the prevention and control of viral diarrhea. Methods Real-time fluorescent RT-PCR was used to detect the nucleic acids of rotavirus, norovirus, sapovirus, astrovirus, and enteric adenovirus collected from diarrhea outpatient cases from 2018 to 2019, and the positive nucleic acid samples were sequenced. Results Among the 398 cases of diarrhea, 184 cases were detected positive, with the positive detection rate of 46.23%. Norovirus infection was the main infection, accounting for 29.40%. The G/P genotype of group A rotavirus was mainly G9P8, accounting for 90.32%. The genotype of norovirus was mainly GII.2[P16], accounting for 33.91%. The genotype of sapovirus was mainly GI.2, accounting for 55.56%. The genotype of astrovirus was HAstV-4, accounting for 100%. The genotype of enteric adenovirus was F41, accounting for 100%. The diarrhea cases were mainly distributed in the fourth quarter, with the positive detection rate of 70.42%, among which norovirus had the highest detection rate, accounting for 53.99%. Conclusion High incidence of viral diarrhea is in winter in Chongqing. The main pathogen of viral diarrhea is norovirus, and the genotypes of norovirus show diversity. It is necessary to prevent the outbreak and epidemic caused by norovirus in winter. In the future, the surveillance of viral diarrhea should be strengthened, and the viral diarrhea gene database should be improved to provide a scientific basis for epidemic prevention and control.

Objective To classify and identify the 53 strains of non-polio enterovirus (NPEV) isolated from acute flaccid paralysis (AFP) cases in Chongqing from 2013 to 2020, and to investigate the genotype distribution of the strains. Methods Commercial real-time fluorescence quantitative polymerase chain reaction (real-time PCR) reagents were used for rapid identification of the strains. The nucleotide sequences of VP1 and VP4 regions were used for genotyping. Results Fifty enteroviruses were identified, 33 (66%) in group A and 17 (34%) in group B. Group C and D enteroviruses were not found in these strains，and 3 strains could not be identified. In this study, EV-A71 was the dominant type, with 11 strains (22%), but EV-A71 strain was not isolated since 2016. The sequences of VP4 region and VP1 region were completely consistent in enterovirus grouping. Conclusion When using commercial real-time PCR reagents for enterovirus typing, the identification results of high CT values may be inaccurate. In the genotyping of enterovirus, the nucleotide sequence of VP4 region is first used for grouping, and then the nucleotide sequence of VP1 region is used for genotyping, which could simplify the experimental process. NPEV isolates from AFP cases in Chongqing showed poor genotype diversity. In order to enrich and improve the enterovirus gene database in Chongqing, it is necessary to carry out research on enterovirus transmitted by respiratory tract.

Objective To understand the epidemiological characteristics and genotype distribution of enterovirus (EV) in influenza-negative influenza-like illness (ILI) cases in Chongqing, and to provide a scientific basis for EV prevention and control. Methods Throat swab samples of influenza-negative ILI cases were collected from surveillance sites. The samples were detected for EV using real-time RT-PCR. The VP4 regions of positive samples were amplified and sequenced for genotyping. Results A total of 3 960 influenza-negative ILI samples were collected from January to December 2021, and 316 (7.98%) of them were EV-positive. EV could be detected in influenza-negative ILI cases in Chongqing all year round. The months with high EV-positive rates were January (11.60%), April (10.56%), May (11.79%), June (12.62%), and July (10.33%). There was a statistically significant difference in the detection rate of EV in ILI cases in different regions, gender, and age groups (χ²=29.647，χ²=4.192，χ²=69.176，P<0.05). A total of 213 EV-positive cases were successfully genotyped, including 17 genotypes of EV-A, EV-B, and EV-C and 5 genotypes of HRV-B. The dominant genotypes were CV-A4 (32.86%), CV-A2 (23.00%), CA-6 (12.21%), and CA-10 (11.74%). EV-D and novel EV were not identified in this study. Conclusion EV is an important pathogen in ILI cases in Chongqing. The prevalence of EV in ILI cases in Chongqing has typical regional, seasonal and population characteristics. Prevention and control should be carried out in Chongqing according to the epidemic characteristics of EV.

Peptides are increasingly important resources for biological and therapeutic development, however, their intrinsic susceptibility to proteolytic degradation represents a big hurdle. As a natural agonist for GLP-1R, glucagon-like peptide 1 (GLP-1) is of significant clinical interest for the treatment of type-2 diabetes mellitus, but its in vivo instability and short half-life have largely prevented its therapeutic application. Here, we describe the rational design of a series of α/sulfono-γ-AA peptide hybrid analogues of GLP-1 as the GLP-1R agonists. Certain GLP-1 hybrid analogues exhibited enhanced stability (t _1/2 > 14 days) compared to t _1/2 (<1 day) of GLP-1 in the blood plasma and in vivo. These newly developed peptide hybrids may be viable alternative of semaglutide for type-2 diabetes treatment. Additionally, our findings suggest that sulfono-γ-AA residues could be adopted to substitute canonical amino acids residues to improve the pharmacological activity of peptide-based drugs.