The rapid emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants that evade immunity elicited by vaccination has posed a global challenge to the control of the coronavirus disease 2019 (COVID-19) pandemic. Therefore, developing countermeasures that broadly protect against SARS-CoV-2 and related sarbecoviruses is essential. Herein, we have developed a lipid nanoparticle (LNP)-encapsulated mRNA (mRNA-LNP) encoding the full-length Spike (S) glycoprotein of SARS-CoV-2 (termed RG001), which confers complete protection in a non-human primate model. Intramuscular immunization of two doses of RG001 in Rhesus monkey elicited robust neutralizing antibodies and cellular response against SARS-CoV-2 variants, resulting in significantly protected SARS-CoV-2-infected animals from acute lung lesions and complete inhibition of viral replication in all animals immunized with low or high doses of RG001. More importantly, the third dose of RG001 vaccination elicited effective neutralizing antibodies against current epidemic XBB and JN.1 strains and similar cellular response against SARS-CoV-2 Omicron variants (BA.1, XBB.1.16, and JN.1) were observed in immunized mice. All these results together strongly support the great potential of RG001 in preventing the infection of SARS-CoV-2 variants of concern (VOCs).

Objective To explore the clinical value of methylation at promoter sites of urine protein kinase Y-linked(PRKY)gene in the early diagnosis of prostate cancer(PCa).Methods Urine samples were collected from 50 suspected PCa patients.After extracting DNA,the methylation levels of the PRKY gene promoter sites cg05163709,cg08045599,and cg05618150 were detected using quantitative methylation-specific PCR(qMSP).Simultaneously,the patients were divided into the benign prostatic hyperplasia(BPH)group and the PCa group.The differences in clinical indicators between the two groups were analyzed,as well as the methylation status of the PRKY gene promoter sites in the urine of the two groups of patients.The receiver operating charac-teristic(ROC)curve of PRKY promoter sites methylation was established,and the area under the curve(AUC)was calculated to analyze the diagnostic value of PRKY promoter sites methylation in PCa,and to perform com-bined diagnosis with clinical indicators.Results The methylation rates of cg05163709 and cg05618150 in urine specimens of PCa patients were significantly higher than those of BPH patients.The AUC for cg05163709 methyla-tion in diagnosing PCa was 0.762,with a sensitivity of 86.70%.It showed better performance in early screening for PCa compared to total prostate specific antigen(tPSA),percentage free prostate specific antigen(f/tPSA)and prostate specific antigen density(PSAD)index.We found that the AUC for cg05618150 methylation in conjunc-tion with PSAD in diagnosing PCa was 0.787,with a sensitivity of 86.70%.The AUC of cg05163709 methylation and PSAD in the joint diagnosis of PCa was 0.855,and the specificity could reach 95.00%.Conclusion The methylation of urine PRKY gene promoter sites cg05163709 and cg05618150 shows high sensitivity and specificity in diagnosing PCa,making them promising biomarkers for early detection of PCa.

The first rate-limiting enzyme of the serine synthesis pathway (SSP), phosphoglycerate dehydrogenase (PHGDH), is hyperactive in multiple tumors, which leads to the activation of SSP and promotes tumorigenesis. However, only a few inhibitors of PHGDH have been discovered to date, especially the covalent inhibitors of PHGDH. Here, we identified withangulatin A (WA), a natural small molecule, as a novel covalent inhibitor of PHGDH. Affinity-based protein profiling identified that WA could directly bind to PHGDH and inactivate the enzyme activity of PHGDH. Biolayer interferometry and LC-MS/MS analysis further demonstrated the selective covalent binding of WA to the cysteine 295 residue (Cys295) of PHGDH. With the covalent modification of Cys295, WA blocked the substrate-binding domain (SBD) of PHGDH and exerted an allosteric effect to induce PHGDH inactivation. Further studies revealed that with the inhibition of PHGDH mediated by WA, the glutathione synthesis was decreased and intracellular levels of reactive oxygen species (ROS) were elevated, leading to the inhibition of tumor proliferation. This study indicates WA as a novel PHGDH covalent inhibitor, which identifies Cys295 as a novel allosteric regulatory site of PHGDH and holds great potential in developing anti-tumor agents for targeting PHGDH.

The thioredoxin system is composed of thioredoxin (Trx), thioredoxin reductase (TR) and reduced nicotinamide adenine dinucleotide phosphate. Trx is an important antioxidant molecule that can resist cell death caused by various stresses and plays a prominent role in redox reactions. TR is a protein containing selenium (selenocysteine), mainly in three forms, i.e. TR1, TR2 and TR3. TR1 mainly distributed in the cytoplasm, TR2 mainly distributed in the mitochondria, and TR3 mainly distributed in the testes. TR can regulate cell growth and apoptosis. After the cell becomes cancerous, the expression of TR increases to promote cell growth and metastasis. Trx system is closely related to neurodegenerative diseases, parasitic infections, acquired immunodeficiency syndrome, rheumatoid arthritis, hypertension, myocarditis and so on. The Trx system can remove the reactive oxygen species (ROS) in the body, keep the inside and outside of the cell in a balanced state, and it interacts with the thioredoxin interacting protein (TXNIP), which plays an important role in the regulation of glucose metabolism and tumor treatment. The Trx system is an important target for drug treatment of many diseases. In this paper, the research progress of the thioredoxin system was reviewed.

Objective To investigate and explore expression status of microRNA-218,and their correlation in serum and tissue samples of prostate cancer patients.Methods The serum and tissue samples of 72 patients in first diagnosised prostate cancer (PCa) and 80 benign prostate hyperplasia (BPH) patients were collected.Serum samples of 162 patients,including 86 patients with androgen-dependent prostate cancer (ADPC) and 76 patients with hormone-refractory prostate cancer (HRPC) were collected.The expression level of microRNA-218 in the tissue and serum samples were detected by specific SYBR Green quantitative real-time polymerase chain reaction (PCR).The correlation between the serum microRNAs and tissue microRNAs expressions tatus were analyzed,and their relationship with clinical characterization were also analyzed.Results The expression level of microRNA-218 in tissues and serum of patients with BPH was higher than that of patients with PCa (P ≤0.001).MicroRNA-218 level in PCa and BPH tissue were both correlated with that in the serum of PCa and BPH (rBPH =0.815,rPCa =0.423).The expression level of microRNAs in tissue and serum samples from PCa were negatively correlated to total prostate specific antigen (tPSA),clinical stages and pathological grade (P ≤0.05).Serum microRNA-218 expression was not significantly different between hormone-dependent PCa patients and newly diagnosed PCa patients,but was significantly lower than that of HRPC patients (P ≤ 0.05),and was positively correlated with tPSA (P ≤0.05).Conclusions The changes of microRNA-218 expression in serum of patients with BPH and prostate cancer can reflect the changes of microRNA-218 expression in tissues.Serum microRNA-218 is expected to be a potential biomarker for early diagnosis and progression of prostate cancer.

Objective To explore the predictive value of dynamic serum phosphorus levels in the evaluation of prognosis in patients with sepsis. Methods A retrospective study was conducted. The septic patients admitted to intensive care unit (ICU) of the Second People's Hospital of Changzhou from January 2016 to June 2017 were enrolled, who were ≥18 years old and whose length of ICU stay > 72 hours. These patients were divided into survival group and death group according to 28-day outcome. The general information, the acute physiology and chronic health evaluation Ⅱ(APACHE Ⅱ) score within 24 hours of ICU admission, the serum phosphorus at 1, 3, 5, 7 days after admission were collected. Receiver operating characteristic curve (ROC) was plotted according to the dynamic serum phosphorus levels and APACHE Ⅱ score for evaluating the predictive value of 28-day prognosis. Kaplan-Meier survival curve was used to analyze the 28-day cumulative survival rate between two groups of patients, who were divided according to the corresponding time of the serum phosphorus cut-off value. Results ① Eighty-five patients with sepsis were enrolled, among whom 25 cases were in the death group and the mortality was 29.4%. APACHE Ⅱ score in the death group was significantly higher than that in the survival group (22.28±3.98 vs. 16.05±5.44, P < 0.01), the rate of using vasoactive drugs was significantly higher than that in the survival group [64.0% (16/25) vs. 31.7% (19/60), P < 0.01], but there was no significant difference in the length of invasive mechanical ventilation and ICU stay between two groups.② The level of serum phosphorus was increased in survival group along with time of the treatment, and the death group showed a downward trend. The levels of serum phosphorus at 3, 5, 7 days after admission to ICU in death group were significantly lower than those in survival group (mmol/L: 0.90±0.24 vs. 1.05±0.19 at 3 days, 0.96±0.16 vs. 1.11±0.17 at 5 days, 0.83±0.19 vs. 1.21±0.14 at 7 days, all P < 0.01).③ROC curve analysis showed that APACHE Ⅱ score and serum phosphorus level on the 7th day could significantly predict 28-day mortality in patients with sepsis, and the areas under ROC curve (AUC) of them were 0.813 and 0.945 respectively (both P < 0.01). The AUC of serum phosphorus level on the 3rd day and 5th day were 0.692 and 0.745 respectively (both P < 0.01). Based on serum phosphorus cut-off value 1.01 mmol/L on the 7th day to evaluate the predictive value of 28-day mortality, the sensitivity was 91.7%, the specificity was 84.0%, the positive and negative likelihood ratios were 5.73 and 0.10 respectively. ④ Kaplan-Meier survival analysis showed that the 28-day survival rate was significantly higher and the length of survival was significantly longer if the serum phosphorus were higher than the cut-off value at different time points of ICU admission. The 28-day survival rate was significantly higher and the length of survival was significantly longer in the patients with serum phosphorus > 1.01 mmol/L than those serum phosphorus ≤ 1.01 mmol/L on the 7th day [28-day survival rate: 93.2% (55/59) vs. 22.7% (5/22), χ2= 49.697, P = 0.000; survival period (days): 27.1±3.6 vs. 19.8±7.8, t = 4.768, P =0.000]. Conclusion The continuous decline of serum phosphorus indicates poor prognosis, and the serum phosphorus level on the 7th day is one of the most important indicator to evaluate the prognosis of patients with sepsis.

Objective:To study the effects of dental fluorosis on the tooth movement following extraction of adjacent tooth in adoles-cents for orthodontic treatment.Methods:50 adolescents were divided into mild(n =1 3),moderat(n =1 0),severe(n =7)and healthy control(n =20)groups according to the fluorosis severity using Dean's index.4 4 were extracted and appliance was applied. X-ray image was taken 1 week and 1 ,2 and 3 months after appliace activation.Tooth movement was measured cephalometrically by Auto CAD.Results:Tooth moving distance was more(P <0.01 )and the alveolar bone resorption area was smaller in fluorosis group than those in healthy control group(P <0.01 )1 ,2 and 3 months after appliance activation.The moving distance was negativelly relat-ed with bone remodling area(P <0.05).Conclusion:Adolescent dental flurosis play an important role in bone remdodeling in extra-tion sites and tooth movement during orthodontic treatment.

Objective The purpose of this study was to study the correlation between dental fluorosis, saliva and plaque fluoride levels and urinary fluoride values in adolescents dental fluorosis. Methods A middle school was chosen as a survey point in the study. Two hundred adolescents were examined the degree of dental fluorosis by Dean's method. These adolescents were divided into four groups according to the severity of fluorosis (n = 52, 40, 28 and 80). Fluoride ion specific electrode was used to measure the fluoride levels in dental plaque, saliva, urinary and drinking water. The differences were analyzed b y ANOVA. Correlation of the fluoride levels between dental plaque, saliva, urine and the degree of dental fluorosis were analyzed by the method of multiple linear regression. Results The average fluoride content of drinking water was (2.20 ± 0.40) mg/L. Compared with controls, the fluoride concentrations in dental plaque, saliva and urine were higher in light, medium and severe dental fluorosis groups [(1.55 ± 0.88), (1.94 ± 0.77), (2.74 ± 0.83) than (0.32 ± 0.20) mg/L; (4.44 ± 1.62), (8.09 ± 0.93), (10.72 ± 0.99) than (0.02 ± 0.01) mg/L;(31.77 ± 6.09), (57.98 ± 1.83), (65.98 ± 2.78) than (13.06 ± 2.11) μg/g, all P<0.05]. Urinary fluoride was correlated with fluoride in saliva and dental plaque (r=0.245, 0.440, all P<0.05). Saliva fluoride was correlated with fluoride in dental plaque (r=0.849, P<0.01). The degree of dental fluorosis was correlated with fluoride in urine and saliva (r = 0.497, 0.896, 0.924, all P< 0.01). The multiple linear regression equation between fluoride in urine and the degree of dent al fluorosis, fluoride in dental plaque and saliva was as follow: y = 1.357 + 1.618x1 + 0.001x2 - 0.331x3 ± 0.69. Conclusions The metabolism of fluoride in body is related with oral fluoride repository in adolescents dental fluorosis. Fluoride in urine is influenced by plaque fluoride level, saliva fluoride concentration and the degree of dental fluorosis.

Objective To prevent the occurrence of postoperative delirium after endoscopic surgery in patients with benign prostatic hyperplasia (BPH). Methods A total of 370 BPH patients receiving endoscopic surgery in our hospital were involved in this study. The clinical parameters including age, other systemic diseases, operation method, operation time and postoperative pain were investigated as predictive risk factors. Then the data were dealt by χ~2 test, single factor analysis or multivariate logistic regression analysis. Results Postoperative delirium occurred in 19 cases (5. 1%). Univariate analysis demonstrated that many factors were significantly correlated with the postoperative delirium in elderly patients, such as age (χ~2 = 7. 37, P<0. 05), other systemic diseases (χ~2=10.26, P<0.05), operation time (χ~2 = 19. 87, P<0.05) and postoperative pain (χ~2= 4.99, P<0. 05). The multivariate logistic regression analysis showed that age (OR = 5. 38, P< 0.05), other systemic diseases (OR = 4. 97, P<0. 05) and operation time (OR = 6. 53, P<0. 05) were important factors for postoperative delirium. Conclusions Paying more attention to the advanced age, giving sufficient preoperative preparation and reducing operation time may help to prevent postoperative delirium.

OBJECTIVETo prepare purified and concentrated coltivirus high titer antigen in order to further detect antibodies against coltivirus in serum sample of patients.

METHODSThe coltivirus in C6/36 cells was cultured and harvested at different time, and the titer was titrated. The virus was purified and concentrated by polyethylene glycol (PEG), and stored at -20 degrees and 4 degrees, with and without glycerol, respectively, then the titer of coltivirus antigen was tested by indirect ELISA. By using the antigen, coltivirus antibodies in serum samples from both suspected Japanese encephalitis (JE) and viral encephalitis (VE) patients were detected.

RESULTSThe highest titer of coltivirus was found at 3-4 weeks of culturing. The antigen titer could be maintained at least for 6 months, especially antigen with glycerol either at 4 degrees or at -30 degrees even for two years. Totally 1141 serum samples from patients diagnosed clinically as JE and VE were tested. The results showed that 130 samples were coltivirus IgM antibody positive and the average positive rate was 11.4% (130/1141). Among 41 samples of paired-serum from patients in Guangzhou Children's Hospital, 9 samples were positive, the positive rate was 22.0% (9/41) in which 5 samples were diagnosed clinically as VE.

CONCLUSIONSStable and purified coltivirus antigen was obtained in order to test coltivirus antibodies as well as development of kits. Coltivirus probably can cause summer-autumn encephalitis in China.

Antibodies, Viral ; blood ; Antigens, Viral ; isolation & purification ; Cell Line ; Coltivirus ; immunology ; Cryopreservation ; methods ; Enzyme-Linked Immunosorbent Assay ; Humans ; Reoviridae Infections ; blood