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.

Objective:To evaluate the efficacy and safety of dupilumab in the treatment of prurigo nodularis (PN) in the real world.Methods:PN patients who were subcutaneously injected with dupilumab for over 12 weeks were collected from the China Type Ⅱ Inflammatory Skin Disease Clinical Research and Standardized Diagnosis and Treatment Project Database from June 2021 to October 2022. Their clinical data were retrospectively analyzed, which included demographic data, and changes in pruritus numeric rating scale (NRS), investigator global assessment for PN-Stage (IGA PN-S), dermatology life quality index (DLQI) and hospital anxiety and depression scale (HADS) scores before and after treatment. Differences in scores before and after treatment, as well as in efficacy between patients with and without a history of atopic diseases, were analyzed using Wilcoxon signed-rank test, paired t-test or chi-square test. Results:A total of 66 PN patients were collected, including 42 males and 24 females, and they were aged 8 to 89 (44.12 ± 24.17) years. Thirty-six patients had a history of atopic diseases, and 27 had a family history of atopic diseases. After 12-week treatment with dupilumab, the pruritus NRS, IGA PN-S and DLQI scores in the 66 patients significantly decreased from the baseline scores (7.00 [5.00, 8.00], 3.00 [3.00, 4.00], 12.00 [7.75, 20.25], respectively) to 3.00 [2.00, 4.25], 2.00 [2.00, 3.00], 5.00 [1.75, 8.25], respectively (all P < 0.001). Among the 66 patients, 39 continued the regular treatment with dupilumab after 12 weeks and were followed up to 16 weeks; their pruritus NRS and IGA PN-S scores at week 16 further decreased compared with those at week 12 (both P < 0.05). There were no significant differences in the proportion of patients showing an improvement of ≥ 4 points in the NRS score or the proportion of patients achieving IGA 0/1 at week 12 between the patients with history of atopic diseases and those without (both P > 0.05). Before treatment, 32 PN patients were accompanied by mild to severe anxiety and/or depression; after 12-week treatment, the HADS-A scores in the 28 patients with anxiety (HADS-A scores > 7 points) and the HADS-D scores in the 20 patients with depression (HADS-D scores > 7 points) significantly decreased compared with their baseline scores (both P < 0.001) ; 18 (56.52%) patients achieved remission in anxiety and depression (both HADS-A and HADS-D scores < 7 points). Among the 66 PN patients, there were 13 minor patients, including 7 males and 6 females, and they were aged 8 to 17 (13.77 ± 3.09) years; after 12-week treatment, their pruritus NRS, IGA PN-S, and DLQI scores significantly decreased compared with the corresponding baseline scores (all P < 0.05) ; 8 minor patients continued dupilumab treatment for 16 weeks, with a further decrease in the IGA PN-S score compared with that at week 12 ( P < 0.05), but without significant differences between the pruritus NRS and DLQI scores at week 16 and those at week 12 (both P > 0.05). Adverse reactions were observed in 7 adult patients, including eye pruritus, local injection reactions, and systemic erythema accompanied by pruritus on the day of injection. No adverse reactions were reported in minor patients. Conclusion:In the real world, dupilumab could markedly alleviate pruritus, skin lesions, anxiety and depression symptoms in PN, improve the quality of life, and exhibited a good safety profile.

Objective:To evaluate the effect of exosomes derived from bone mesenchymal stem cells (BMSCs-EXO) on the postoperative cognitive function and silent infomation regulator 1 (SIRT1)/ nuclear factor kappa B (NF-κB) signaling pathway in aged mice.Methods:BMSCs-EXO were isolated by differential centrifugation method and then identified. Twenty healthy male C57BL/6 aged mice, aged 18 months, weighing 35-40 g, were divided into 4 groups ( n=5 each) using a random number table method: sham operation group (Sham group), operation group (O group), BMSCs-EXO group and EX527 (SIRT1 inhibitor)group. The abdomen regions were shaved for sterilization without exploratory laparotomy in Sham group. Exploratory laparotomy was performed in O group. BMSCs-EXO 50 μg was injected through the tail vein at 1 h before surgery in BMSCs-EXO group. EX527 5 mg/kg was intraperitoneally injected daily at 1-3 days before surgery, and BMSCs-EXO 50 μg was injected through the tail vein at 1 h before surgery in EX527 group. Morris water maze test was used to evaluate the learning and memory ability for 5 consecutive days staring from the 1st day after surgery. Mice were sacrificed at 1 h after the end of Morris water maze test on day 5 after surgery, and the hippocampal tissues were collected for observation of the pathological changes of hippocampal CA1 region and for determination of the expression of tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6) and IL-1β mRNA (quantitative real-time polymerase chain reaction) and SIRT1 and NF-κB p65 (by Western blot). Results:Compared with Sham group, the escape latency was significantly prolonged, the times of original platform crossing were decreased, the swimming time spent in the original platform quadrant was shortened, the expression of tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6) and IL-1β mRNA was up-regulated, the SIRT1 expression was down-regulated, the NF-κB p65 expression was up-regulated ( P<0.05), and the pathological changes of hippocampal tissues in CA1 region were found in O group. Compared with O group, the escape latency was significantly shortened, the times of original platform crossing were increased, the swimming time spent in the original platform quadrant was prolonged, the expression of TNF-α, IL-6 and IL-1β mRNA was down-regulated, the expression of SIRT1 was up-regulated, the expression of NF-κB p65 was down-regulated ( P<0.05), and the pathological changes of hippocampal tissues in CA1 region were significantly attenuated in BMSCs-EXO group ( P<0.05). Compared with BMSCs-EXO group, the escape latency was significantly prolonged, the times of original platform crossing were decreased, the swimming time spent in the original platform quadrant was shortened, the expression of TNF-α, IL-6 and IL-1β mRNA was up-regulated, the SIRT1 expression was down-regulated, the NF-κB p65 expression was up-regulated ( P<0.05), and the pathological changes of hippocampal tissues in CA1 region were accentuated in EX527 group. Conclusions:BMSCs-EXO can improve the postoperative cognitive function in aged mice, and the mechanism may be associated with the activation of SIRT1/NF-κB signaling pathway.

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.

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.

Background::Endoscopic resection is increasingly used in the treatment for early gastric cancer (EGC); however, about 15% of endoscopic submucosal dissection (ESD) cases report non-curative resection. The efficacy of different remedial interventions after non-curative ESD for EGC remains controversial. This meta-analysis aimed to compare the long-term outcomes of additional surgery and non-gastrectomy treatment for EGC patients who underwent non-curative ESD.Methods::All relevant studies published up to October 2021 were systematically searched in the PubMed, Web of Science, and Embase databases. The medical subject headings terms "early gastric cancer," "gastrectomy," "endoscopic submucosal dissection," and their related free keywords were used to search relevant articles without restrictions on regions, publication types, or languages. The Newcastle–Ottawa Quality Assessment Scale was used to evaluate the quality of the included studies. Odds ratios (ORs) with 95% confidence intervals (CIs) of 5-year overall survival (OS), disease-specific survival (DSS), disease-free survival (DFS) and hazard ratios (HRs) with 95% CIs of OS were calculated using a random- or fixed-effects model.Results::This meta-analysis included 17 retrospective cohort studies with 5880 patients, of whom 3167 underwent additional surgery and 2713 underwent non-gastrectomy. We found that patients receiving additional gastrectomy had better 5-year OS (OR = 3.63, 95% CI = 3.05–4.31), DSS (OR = 3.22, 95% CI = 2.22–4.66), and DFS (OR = 4.39, 95% CI = 1.78–10.82) outcomes than those receiving non-gastrectomy treatments. The pooled HR also showed that gastrectomy following non-curative ESD significantly improved OS (HR = 0.40, 95% CI = 0.33–0.48). In addition, elderly patients benefited from additional surgery in consideration of the 5-year OS (HR = 0.54, 95% CI= 0.41–0.72).Conclusions::Compared with non-gastrectomy treatments, additional surgery offered better long-term survival outcomes for patients with EGC who underwent non-curative ESD.

Objective:To investigate changes in skin microecological structures and functions between acute and remission phases in adult patients with severe atopic dermatitis (AD) .Methods:From October 2019 to November 2020, skin scale specimens were collected from 5 body sites (cheeks, cubital fossa, back of the hand, abdomen, lower limbs) of 4 adult patients with severe AD in the acute and remission phases, who visited the outpatient clinic of Guangzhou Institute of Dermatology. The next-generation high-throughput sequencing was performed for metagenomic sequencing to construct the microbial gene catalogue of these specimens, followed by gene annotation and bioinformatics analysis for each sample.Results:A total of 18 phyla, 37 classes, 73 orders, 142 families, 237 genera, and 331 species were identified in the skin specimens from the 4 patients with severe AD. The patients with AD in the remission phase showed significantly increased diversity of skin microbiota and markedly different relative abundance of skin microorganisms compared with those in the acute phase (both P < 0.05). At the microbial species level, Staphylococcus aureus showed the highest impact on the acute phase of AD, while Staphylococcus epidermidis, Moraxella osloensis, Francisella sp., Staphylococcus cohnii, Staphylococcus warneri, Malassezia globosa and Malassezia restricta were enriched in the remission phase of AD with the absolute value of the common logarithm of the linear discriminant analysis score > 2 (Kruksal-Wallis test, all P < 0.05). As KEGG pathway enrichment analysis showed, the differentially abundant genes were annotated into a total of 355 functional pathways, of which 38 pathways were significantly enriched (all P < 0.05), mainly involving Staphylococcus aureus infection, tryptophan metabolism, histidine metabolism, nitrogen metabolism, metabolism of arginine and proline, biosynthesis and degradation of valine, leucine and isoleucine, fatty acid degradation, peroxisome proliferator-activated receptor signaling pathway, etc. Conclusion:The skin microecological structure significantly differed between the acute and remission phases among the patients with severe AD, which may be related to multiple functional pathways, such as Staphylococcus aureus infection, tryptophan metabolism, histidine metabolism and nitrogen metabolism.

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.

In clinical application, a microneedle system that continuously delivers drugs is of great value for the delivery of some vaccines and hormone drugs. In this study, a controlled-release chitosan-based microneedle array (PVA/CS-MN) was designed, combining microneedle patches with drugs for controlled-release of drugs. Here we report the optimization of the preparation process of PVA/CS-MN. The appearance, morphology, mechanical properties, dissolution and swelling properties, and in vitro penetration properties of the MN arrays were characterized. The PVA/CS-MN prepared by the optimal process showed good morphology and mechanical properties. PVA/CS-MN can smoothly open microchannels on the skin and achieve controllable dissolution and swelling functions. Ascorbic acid (l-ascorbic acid) was used as a model drug to prepare a Vc-PVA/CS-MN. In vitro transdermal diffusion experiments showed that the Vc-PVA/CS-MN released about 57% of the drug within 1 h. About 66.7% of the drug was slowly released within 12 h, and a total of 92% of the drug was released after 7 days. The controllable sustained-release properties and excellent drug delivery efficiency of PVA/CS-MN provide a new option for sustained transdermal drug delivery.
Ascorbic Acid ; Chitosan ; Delayed-Action Preparations ; Drug Delivery Systems ; Hormones ; Vaccines