ObjectiveTo understand the whole genome characteristics and the information for genetic evolution in the two coxsackievirus A2 (CVA2) strains isolated from patients with herpangina in Shanghai, and to provide a scientific basis for the prevention and treatment of herpetic angina. MethodsTwo CAV2 strains isolated from patients with herpetic angina in Shanghai were performed whole genome sequencing and analysis for phylogenetics, nucleotide homology, and evolution. ResultsA phylogenetic analysis of the VP1 region revealed that the two Shanghai strains both belonged to CVA2 genotype D, with the highest homology to OL357660, a strain from Yunnan. The average nucleotide identity (ANI) of the whole genome between the two Shanghai strains was 98.88%, and the ANI of the whole genome comparisons to other CVA2 genotype D strains and CVA2 genotypes A-C strains ranged from 84.64% to 97.42% and from 79.21% to 84.20%, respectively. The two Shanghai strains had low homology in the 3D region compared to the existing CVA2 strains. The phylogenetic analysis and sliding window nucleotide similarity analysis indicated that the two Shanghai strains and the Yunnan OL357660 strain might constitute a new genetic lineage. ConclusionThe two CVA2 strains isolated for the first time in Shanghai are assigned to genotype D (GenBank: PQ130039 and PQ130040), which is identical to the existing subtype prevalent in China. As represented by the Shanghai strains, a new CVA2 genetic lineage is been identified. This study has enriched the data on genetic evolution and genetic variation of CVA2 in Shanghai, indicating the requirement to strengthen surveillance for the epidemiological pattern of CVA2.

Glioblastoma (GBM) is a highly aggressive primary brain tumor characterized by poor prognosis. Conventional chemo-radiotherapy demonstrates limited therapeutic efficacy and is often accompanied by significant side effects, largely due to factors such as drug resistance, radiation resistance, the presence of the blood-brain barrier (BBB), and the activation of DNA damage repair mechanisms. There is a pressing need to enhance treatment efficacy, with BRD4 identified as a promising target for increasing GBM sensitivity to therapy. Lacking small molecule inhibitors, BRD4 can be degraded using PROteolysis Targeting Chimera (PROTAC), thereby inhibiting DNA damage repair. To deliver PROTAC, SIAIS171142 (SIS) effectively, we designed a responsive nanocapsule, MPL_(SS)P@SIS, featuring GBM-targeting and GSH-responsive drug release. Modified with 1-methyl-l-tryptophan (MLT), nanocapsules facilitate targeted delivery of SIS, downregulating BRD4 and sensitizing GBM cells to radiotherapy and chemotherapy. After intravenous administration, MPL_(SS)P@SIS selectively accumulates in tumor tissue, enhancing the effects of radiotherapy and temozolomide (TMZ) by increasing DNA damage and oxidative stress. GSH activates the nanocapsules, triggering BRD4 degradation and hindering DNA repair. In mouse models, the nanosensitizer, combined with TMZ and X-ray irradiation, efficiently inhibited the growth of GBM. These findings demonstrate a novel PROTAC-based sensitization strategy targeting BRD4, offering a promising approach for effective GBM therapy.

Objective To analyze the incidence and mortality of pancreatic cancer in 2022 globally and in China based on the Global Cancer Statistics 2022 published by the International Agency for Research on Cancer,considering characteristics such as gender,age,and human development index(HDI).Methods Pancreatic cancer data from 185 countries and regions were sourced from the GLOBOCAN 2022 database,and HDI data were compiled based on the Human Development Report 2022 published by the United Nations Development Programme.Cancer data were stratified by age,gender,and HDI to describe the prevalence of pancreatic cancer globally and in China.Pearson correlation analysis was used to evaluate the correlation of standardized incidence rate(SIR),standardized mortality rate(SMR),and mortality-to-incidence ratio(M/I)with HDI.Results In 2022,the number of pancreatic cancer incident cases worldwide was 510 992,ranking 12th among all cancer incidents,with an SIR of 4.7 per 100 000(ranking 15th).The number of pancreatic cancer deaths globally was 467 409,ranking 6th among all cancer deaths,with an SMR of 4.2 per 100 000(ranking 9th).In China,the number of pancreatic cancer incident cases was 118 672(ranking 10th among all cancer incidents),accounting for 23.22%of the global pancreatic cancer incidents,with an SIR of 4.4 per 100 000(ranking 13rd).The number of pancreatic cancer deaths in China was 106 295(ranking 6th among all cancer deaths),accounting for 22.74%of the global pancreatic cancer deaths,with an SMR of 3.9 per 100 000(ranking 8th).The incidence,mortality,SIR,and SMR in males were higher than those in females both globally and in China.SIR and SMR were positively correlated with HDI(r=0.77 and 0.77,both P＜0.001),while M/I was negatively correlated with HDI(r=-0.43,P＜0.001).The incidence,mortality,SIR and SMR of pancreatic cancer showed an increasing trend with age,and rapidly increased from 45-49 years old.Conclusion The disease burden of pancreatic cancer is serious globally and in China.The incidence and mortality of pancreatic cancer show an upward trend with age,and they are higher in males than in females.HDI is positively correlated with SIR and SMR of pancreatic cancer,while negatively correlated with M/I.

Icariin,which belongs to the class of flavonoids,is the main active ingredient of the traditional tonic Chinese herb Epimedii Folium.Modern studies have shown that icariin has a wide range of effects on the male reproductive system.It has various pharmacological activities such as regulating cell proliferation and apoptosis,antioxidants,promoting testosterone secretion,improving erectile function,inhibiting prostate cancer cell migration,invasion,and regulating cell cycle.It has research value and application prospects in the field of urology and assisted reproduction.Therefore,Icariin's pharmacological effects and molecular mechanisms on the male reproductive system are reviewed in this paper combined with literature visualization analysis.It is expected to provide a theoretical basis for the therapeutic value development and application of icariin in male reproductive health.

Objective To conduct Rh blood group serological testing and third-generation sequencing(TGS)on 22 RhD variant voluntary blood donors in Chongqing and explore the phenotypic distribution and genotyping of RhD variants in Chongqing.Methods From January to August 2023,individuals who participated in blood donation in our blood center were selected as the study objects.RhD variant phenotype identification was performed using routine serological methods.Once the RhD variants were identified,tests on different antigenic epitopes of RhD were conducted using a D-screen assay kit.Furthermore,after the genomic DNA from 22 RhD variant blood samples was extracted,imbraided primers design and multi-segment amplification and splicing were used to sequence the full-length RHD gene for TGS.The RHD gene sequence was analyzed using SnapGene software.Results Among the 22 RhD variants,8 were DVI type 3(36.36%),with the main mutation of RHD-CE(3-6)-D hybrid allele.Six cases(27.27%)showed partial weak D15 type,with the main mutation of c.845G>A.There were 6 cases of Asia type Del(27.27%),with the main mutation of c.1227G>A.One case was weak D17 type with a mutation of c.340C>T and 1 case speculated to be partial D(c.491A>T,p.Asp164Val,missense mutation).Conclusion The most common RhD variant phenotype among blood donors in Chongqing is DVI type 3,and the full-length haplotype sequence of RHD variant alleles can be obtained by Pacific Bioscience single-molecule real-time sequencing(SMRT).

Objective:To elucidate the etiological and epidemiological characteristics and epidemiological patterns of viral acute respiratory infections (ARI) in Shanghai during 2023, with the aim of providing robust laboratory evidence for effective prevention and control strategies against related respiratory diseases and facilitating risk assessment.Methods:Respiratory pathogens were detected in the clinical surveillance specimens submitted by sentinel hospitals through multiplex PCR, as part of the multi-pathogen surveillance of acute respiratory infections in Shanghai during 2023. The obtained detection result were statistically analyzed in conjunction with sample information.Results:The positive detection rate of viral pathogens in 2023 was 21.17% (984/4 648), with rates of 33.53% (504/1 503) observed in ILI cases and 15.62% (480/3 145) in SARI cases. Influenza A virus (FluA) was the predominant virus detected, accounting for 13.7% (637/4 648). Other viruses identified in the surveillance samples included influenza B virus (Flu B), human rhinovirus/enterovirus (HRV/HEV), respiratory syncytial virus (RSV), human metapneumovirus (HMPV), parainfluenza virus (PIV), adenovirus (ADV) and human bocavirus (HBoV). Regarding temporal distribution, HRV/HEV and RSV exhibited the highest detection rates during the second quarter at 2.27% each (28/1 236). PIV had its peak during the third quarter at a rate of 2.49% (35/1 405), and HMPV showed prevalence mainly during the third and fourth quarters, with detection rates of 2.63% (37/1 405) and 2.35% (32/1 360), respectively.Conclusions:In acute respiratory infection surveillance cases in Shanghai in 2023, Flu A emerged as the predominant respiratory pathogen. The detection rate of HMPV ranked second only to Flu A, while other respiratory viruses such as HRV/HEV, RSV, and PIV were detected during different seasons and co-circulated. The prevalence of various respiratory viruses varied among different infected populations and over times.

Objective:To evaluate alteration of autograft function by pathological types after total parathyroidectomy (tPTX) plus autotransplantation (AT) in patients of hyperthyroidism.Methods:A total of 51 patients with end-stage chronic renal failure who underwent total parathyroidectomy with autologous forearm transplantation from Mar 2017 to Feb 2021 were divided into chief cell type (CC) and oxyphil cell type (OC) according to dominating graft cell type. iPTH, calcium, phosphorus and ALP levels were compared between the two groups from the perioperative period to 6 months and the 3D ultrasonography was performed at 6 months to cocalculate the size of the autograft.Results:Between the two groups, there were no statistically significant differences in iPTH, blood calcium, blood phosphorus, or ALP levels pre-,and 30 minutes, one month post surgery (all P>0.05). On three months, there was no significant difference in ALP levels [CC group: (99±23) U/L, OC group: (89±35) U/L, t=0.776, P=0.442]. At 6 months the PTH level [CC group: (290±77) pg/ml, OC group: (246±59) pg/ml, t=2.034, P=0.047], and blood calcium [CC group: (2.62±0.65) mmol/L, OC group: (2.21±0.20) mmol/L, t=2.531, P=0.015] blood phosphorus [CC group: (1.38±0.28) mmol/L, OC group: (1.68±0.34) mmol/L; t=-3.269, P=0.002], were all in favor of CC group. By 3D ultrasnography at 6 months the size of autograft was larger in CC group than in OC group [V cc=(2.17±0.37) cm 3,V oc=(1.85±0.29) cm 3, t=3.172, P<0.05]. Recurrences at 1 year after surgery were not significantly different between the two groups ( ncc=3, noc=1, t=0.277, P>0.05). Conclusion:The biological activity of CC-type grafts is higher than that of OC suggesting a longer functioning period as a parathyroid autograft.

Purpose To explore the feasibility of using virtual non-contrast images derived from spectral CT for pulmonary angiography(CTPA)to replace true non-contrast scan of chest,in order to reduce radiation dose.Materials and Methods Fifty-six patients undergoing CTPA examination in the First Affiliated Hospital of Dalian Medical University were prospectively enrolled.All patients underwent both conventional chest CT and spectral CTPA scan.On both virtual unenhanced images and true unenhanced images,CT values and standard deviation values of the pulmonary parenchyma in the level of thoracic aorta,main pulmonary artery,erector spine,as well as pulmonary apex,tracheal carina,and lung base were measured.Signal noise ratio and contrast noise ratio of thoracic aorta and pulmonary artery were calculated.The image quality and iodine residue of the two groups was evaluated.The consistency of subjective scores was also assessed.Dose length product,CT dose index volume and contrast agent dosage were recorded.The CT value,signal noise ratio,contrast noise ratio,radiation dose and subjective score of each region of interest in true unenhanced and virtual unenhanced images were compared.Results The inter-observer subjective scores were consistent(Kappa=0.984-0.992,P＜0.05).The subjective scores of the chest true unenhanced and virtual unenhanced images were 4.75±0.65 and 4.65±0.49,respectively,with no statistical difference(t=0.630,P=0.437).There was no significant difference in CT values of thoracic aorta,pulmonary artery and lung tissues between true unenhanced and virtual unenhanced images(P＞0.05).There was no significant difference in signal noise ratio and contrast noise ratio between pulmonary artery and thoracic aorta(P＞0.05).Replacing conventional chest scan with virtual unenhanced images of CTPA reduced the radiation dose by approximately 55％,reducing from(7.27±1.74)mSv to(3.26±0.84)mSv.Conclusion It is feasible to use CTPA virtual non-contrast images to replace conventional unenhanced CT chest imaging for lung disease screening,since it can significantly reduce the radiation dose to patients.