Objective To investigate the relationship between the expression of keratin 15(KRT15)and keratin 18(KRT18)proteins in colorectal cancer tissue and their clinicopathological features and prognosis.Methods A total of 97 patients with colorectal cancer who underwent surgical treatment in a hospital from June 2018 to June 2019 were selected as the study objects.Immunohistochemistry was used to detect the ex-pression of KRT15 and KRT18 protein in colorectal cancer tissues and adjacent tissues,and the differences of KRT15 and KRT18 protein expression in colorectal cancer patients with different clinicopathological features were compared.The patients with colorectal cancer were followed up for 3 years after discharge,and their o-verall survival(OS)during the follow-up period was analyzed.Kaplan-Meier survival curve and Log-rank test were used to analyze the difference in OS rate among colorectal cancer patients with different KRT15 and KRT18 protein expression.Univariate and multivariate COX proportional regression analysis was performed to analyze the factors affecting the prognosis of patients with colorectal cancer.Results The positive expres-sion rates of KRT15 and KRT18 protein in colorectal cancer tissues were higher than those in adjacent tis-sues,and the difference was statistically significant(P＜0.05).The positive expression rates of KRT15 and KRT18 protein in colorectal cancer tissues of patients with low differentiation,TNM Ⅲ stage,perineural inva-sion and preoperative carcinoembryonic antigen(CEA)level ≥5 ng/mL were higher than those of patients with medium-high differentiation,TNM Ⅰ-Ⅱ stage,without perineural invasion and preoperative CEA level＜5 ng/mL,the difference was statistically significant(P＜0.05).The 3-year OS rates of colorectal cancer patients with positive expression of KRT15 and KRT18 protein were 64.29％and 60.00％respectively,which were lower than those of patients with negative expression of KRT15 and KRT18 protein(83.64％and 85.96％respec-tively),and the difference was statistically significant(x2=6.497,7.987,P＜0.05).Multivariate COX pro-portional regression analysis showed that TNM stage Ⅲ,positive expression of KRT15 protein and positive expression of KRT18 protein were risk factors affecting the survival of patients with colorectal cancer(P＜0.05).Conclusion The expression of KRT15 and KRT18 protein in colorectal cancer tissues can provide ref-erence for prognosis assessment of patients with colorectal cancer.

Objective To explore the value of baseline plasma soluble type 2 myeloid cell trigger receptors(sTREM2)in evaluation for early hematoma enlargement in elderly patients with spontan-eous cerebral hemorrhage(SCH).Methods Clinical data of 240 patients with acute SCH admitted to our hospital from January 2020 to August 2022 were collected and analyzed retrospectively.According to the expansion of the hematoma volume,they were divided into non-expansion group(172 cases)and expanded group(68 cases).Baseline head CT scanning was performed in all patients within 24 h of onset,clinical and imaging data were analyzed,and the volume of cerebral hematoma was calculated.Blood samples were collected immediately after admission and sTREM2 and galectin-3 levels were measured.Results Compared with the non-expansion group,the ex-panded group had larger cerebral hematoma volume,and increased levels of sTREM2,galectin-3,hs-CRP and TNF-a at admission(P＜0.01).Pearson correlation analysis showed that the expres-sion levels of sTREM2 and galectin-3 were positively correlated with cerebral hematoma at ad-mission(r=0.784,P=0.012;r=0.815,P=0.004).ROC curve analysis indicated that the sensi-tivity of combined serum sTREM2 and galectin-3 levels was significantly higher than that of sin-gle detection(85.59％vs 73.73％and 64.41％,P＜0.05),and the AUC value was 0.896(95％CI:0.741-0.932).Conclusion The baseline plasma level of sTREM2 is significantly increased in eld-erly SCH patients after early hematoma expansion.So,sTREM2 can be used as a risk marker for early expansion of hematoma,and its combined detection with galectin-3 shows higher diagnostic value.

OBJECTIVE: Anemoside B4 (AB4), the most abundant triterpenoidal saponin isolated from Pulsatilla chinensis, inhibited influenza virus FM1 or Klebsiella pneumoniae-induced pneumonia. However, the anti-SARS-CoV-2 effect of AB4 has not been unraveled. Therefore, this study aimed to determine the antiviral activity and potential mechanism of AB4 in inhibiting human coronavirus SARS-CoV-2 in vivo and in vitro. METHODS: The cytotoxicity of AB4 was evaluated using the Cell Counting Kit-8 (CCK8) assay. SARS-CoV-2 infected HEK293T, HPAEpiC, and Vero E6 cells were used for in vitro assays. The antiviral effect of AB4 in vivo was evaluated by SARS-CoV-2-infected hACE2-IRES-luc transgenic mouse model. Furthermore, label-free quantitative proteomics and bioinformatic analysis were performed to explore the potential antiviral mechanism of action of AB4. Type I IFN signaling-associated proteins were assessed using Western blotting or immumohistochemical staining. RESULTS: The data showed that AB4 reduced the propagation of SARS-CoV-2 along with the decreased Nucleocapsid protein (N), Spike protein (S), and 3C-like protease (3CLpro) in HEK293T cells. In vivo antiviral activity data revealed that AB4 inhibited viral replication and relieved pneumonia in a SARS-CoV-2 infected mouse model. We further disclosed that the antiviral activity of AB4 was associated with the enhanced interferon (IFN)-β response via the activation of retinoic acid-inducible gene I (RIG-1) like receptor (RLP) pathways. Additionally, label-free quantitative proteomic analyses discovered that 17 proteins were significantly altered by AB4 in the SARS-CoV-2 coronavirus infections cells. These proteins mainly clustered in RNA metabolism. CONCLUSION Our results indicated that AB4 inhibited SARS-CoV-2 replication through the RLR pathways and moderated the RNA metabolism, suggesting that it would be a potential lead compound for the development of anti-SARS-CoV-2 drugs.

Objective To explore the abnormal changes of resting state functional connectivity of pain networks in patients with cervical discogenic pain(CDP).Methods The resting-state functional magnetic resonance imaging(rs-fMRI)data of 40 patients with CDP and 40 age-and gender-matched healthy controls(HC)were collected.The seed of posterior insula(PI)was used to define the pain network,and seed-based whole-brain functional connectivity analyses were performed to explore the difference of functional connectivity between CDP patients and HC,the associations between functional connectivity and clinical measures were analyzed.Results The functional connectivity between bilateral PI and bilateral thalamus(THA)was increased,and the functional connectivity between left PI and middle cingulate cortex(MCC),left postcentral gyrus(PoCG)and MCC were decreased in CDP patients.Moreover,the func-tional connectivity between right PI and left THA was positively correlated with visual analogue scale(VAS),and the functional connectivity between left PoCG and MCC was negatively correlated with VAS.Conclusion Functional connectivity abnormalities exist in pain network resting state of CDP patients,which may provide an imaging basis for revealing the neuropathological mechanism of pain in CDP patients.

Objective To visualize and analyze the researches on transcranial direct current stimulation(tDCS)for stroke rehabilita-tion. Methods The Web of Science core collection and CNKI were searched for literature on the use of tDCS for stroke reha-bilitation,since the establishment of the database until March 31st,2023.The literature was analyzed wtih Cite-Sapce 6.2.R2 in term of disciplines,articles number,countries,keywords and co-citation,etc. Results A total of 732 articles in English and 322 articles in Chinese were included,and the number of articles was on the rise.The country with the largest number of publications was the United States,and the journal with the high-est citation frequency was Stroke.The keywords with high attention in recent years were virtual reality,upper limb and transcranial magnetic stimulation.The clustering words of co-cited literature were aphasia,homeostatic plasticity,and motor recovery,etc. Conclusion The researches about tDCS for stroke rehabilitation are increasing year by year,and the research fields are diversified.The hotspots include rehabilitation for motor and speech,and combination with other therapy,such as repetitive transcranial magnetic stimulation and acupuncture.The combination of tDCS with new rehabilitation protocols such as brain-computer interfaces and virtual reality,as well as the selection of individualized stimula-tion parameters to construct patient-centered tDCS models may be hot in the future.

Objective:To study the biological traits and mutations of the influenza A (H3N2) virus in order to produce a vaccine and offer references for controlling and preventing influenza epidemics.Methods:Four strains of the influenza A(H3N2) virus were chosen from the Huai′an surveillance network laboratory. Nucleic acid extraction, library building, and sequencing (CridION x5 MKI Nanopore) were used to produce the whole-genome sequences. Using homologous alignments of whole-genome sequences, phylogenetic tree construction, and amino acid variant screening, bioinformatics analysis was carried out.Results:The nucleotide identity between 8 gene segments ranged from 97.1% to 100.0%. The gene that differed the most from the reference sequences was HA (97.1%-99.9%), and the gene that differed the least was MP (98.6%-99.9%). The HA gene (3.06%) and MP gene (1.43%) were the regions with the greatest and lowest frequencies of nucleotide site change, respectively. The rates of nucleotide change varied significantly between the genes ( χ2=14.293, P=0.046). Four influenza A(H3N2) virus strains′ whole-genome phylogenies from each of the eight gene segments maintained a roughly consistent topological structure. One strain was linked to the 3C.2a1b.1b clade, which was lost at the 142NWT, 149NGT(HA1), and 436NLS(NA). Three strains were linked to the 3C.2a1b.2a.1a clade lineage. Amantadine and NA inhibitors were effective against all Huai′an strains. Conclusions:The antigenicity of one strain of Huai'an strain changed and its matching with the vaccine strain of that year was low. It is suggested that the genetic surveillance of H3N2 influenza virus should be continuously strengthened to provide scientific basis for influenza prevention and control and influenza vaccine screening.

Objective To comprehend the present condition of sustaining within familial pulmonary rehabilitation for COPD patients,alongside exploring the factors that impact this continuity.Methods A convenience sampling method was used to select 392 COPD patients from outpatient clinics of 2 tertiary-level A hospitals and 1 community health service center in Huaihua in Hunan Province from December 2023 to February 2024 as survey respondents.Patients were surveyed using the general information questionnaire,the COPD Assessment Test,the Modified Medical Research Council Dyspnea Scale,the Exercise Benefits/Barriers Scale,and the Brief 2-Way Social Support Scale.Results We sent out 392 questionnaires and collected 362 valid ones,with an effective response rate of 92.47％.The percentage of COPD patients who never performed home pulmonary rehabilitation was 56.08％,and the maintenance time of health behaviors in home pulmonary rehabilitation was 17.40％for 1-3 months,7.18％for 4-6 months,4.70％for 7-12 months,and 14.64％for more than 1 year.The results of multiple linear regression analysis showed that exercise place,pulmonary rehabilitation health education,exercise habits before having COPD,perceived level of exercise behavior,and two-way social support were influential factors affecting the maintenance of health behaviors in pulmonary rehabilitation in the families of COPD patients,which explained 38.5％of the variability.Conclusion Patients with COPD have a low level of maintenance of health behaviors in home pulmonary rehabilitation,and health education on exercise rehabilitation for COPD patients and caregivers should be strengthened to enhance patients'level of exercise perception and ability to utilize social support.

Objective:To explore the influence of deep learning reconstruction algorithm combined with low-dose CT on image quality and bone mineral density measurement and the application value in opportunistic osteoporosis screening.Methods:A total of 119 patients (aged ≥40 years) who underwent a combined chest and upper abdominal low-dose scan were prospectively included. All the images were reconstructed using filtered back projection(FBP) alogrithm, hybrid model-based adaptive statistical iterative reconstruction (ASIR-V) 50% and three levels of deep learning reconstruction algorithm respectively. Bone mineral density (BMD) values for different reconstruction conditions were measured and compared using asynchronous quantitative CT software. The signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) of descending aorta, liver and spleen were calculated, and the image noise was the standard deviation of anterior abdominal wall fat and the image quality was objectively evaluated by using the five-point subjective evaluation method. The objective and subjective image quality of different body parts with different reconstruction method was compared.Results:There was no statistical difference in BMD with different reconstruction method ( P > 0.05). Compared with ASIR-V 50%, the SNRs of high level deep learning image reconstruction (DLIR-H)in descending aorta, latissimus dorsi, liver and spleen were increased by 103.88%, 125.09% and 136.13% respectively, and the image noise was decreased by 55.98%. Both the CNR and subjective scores (except the ability to display lung lesions) of DLIR-H were better than those of DLIR-L and ASIR-V 50% ( χ2 =158.31-275.35, P<0.001). Conclusions:The deep learning algorithm does not affect the accuracy of bone mineral density measurement, and the image quality is better than that of ASIR-V 5%. Deep learning algorithm combined with low-dose CT can be used for opportunistic osteoporosis screening.

Objective To investigate the predictive value of capillary leakage index(CLI)combined with mean platelet volume to platelet count ratio(MPV/PLT)for acute respiratory distress syndrome(ARDS)in patients with abdominal sepsis.Methods Patients with abdominal sepsis admitted to the Affiliated Hospital of Xuzhou Medical University from July 2016 to May 2022 were retrospectively se-lected,and divided into ARDS group and non-ARDS group according to whether they were complicated with ARDS.The clinical data of the two groups were compared.The risk factors of ARDS in patients with abdominal sepsis were analyzed by multivariate Logistic regres-sion.Receiver operator characteristic(ROC)curve was used to evaluate the predictive efficacy of CLI combined with MPV/PLT for ARDS occurrence in patients with abdominal sepsis.Results A total of 250 patients with abdominal sepsis were enrolled,including 113 pa-tients in the ARDS group and 137 patients in the non-ARDS group.Multivariate Logistic regression analysis showed that Sequential Or-gan Failure Assessment(SOFA)score,Acute Physiology and Chronic Health Evaluation Ⅱ(APACHE Ⅱ)score,CLI and MPV/PLT were independent risk factors for predicting ARDS in abdominal sepsis.ROC curve analysis results showed that the area under the curve(AUC)of the combined index(CLI and MPV/PLT)was the largest,which was 0.810,followed by the APACHE Ⅱ score,which was 0.781.The AUC of MPV/PLT,SOFA score and CLI were 0.770,0.749 and 0.704,respectively.When the optimal cut-off value was 0.3,the specificity was 89.4％and the sensitivity was 61.3％,which was superior to the value of single index in the diagnosis and pre-diction of ARDS in patients with abdominal sepsis.Conclusion CLI and MPV/PLT can well predict ARDS in patients with abdominal sepsis,and when they are combined,the prediction value is higher.

The global COVID-19 coronavirus pandemic has infected over 109 million people, leading to over 2 million deaths up to date and still lacking of effective drugs for patient treatment. Here, we screened about 1.8 million small molecules against the main protease (M^pro) and papain like protease (PL^pro), two major proteases in severe acute respiratory syndrome-coronavirus 2 genome, and identified 1851M^pro inhibitors and 205 PL^pro inhibitors with low nmol/l activity of the best hits. Among these inhibitors, eight small molecules showed dual inhibition effects on both M^pro and PL^pro, exhibiting potential as better candidates for COVID-19 treatment. The best inhibitors of each protease were tested in antiviral assay, with over 40% of M^pro inhibitors and over 20% of PL^pro inhibitors showing high potency in viral inhibition with low cytotoxicity. The X-ray crystal structure of SARS-CoV-2 M^pro in complex with its potent inhibitor 4a was determined at 1.8 Å resolution. Together with docking assays, our results provide a comprehensive resource for future research on anti-SARS-CoV-2 drug development.
Humans ; Antiviral Agents/chemistry* ; COVID-19 ; COVID-19 Drug Treatment ; High-Throughput Screening Assays ; Molecular Docking Simulation ; Protease Inhibitors/chemistry* ; SARS-CoV-2/enzymology* ; Viral Nonstructural Proteins