Safety, immunogenicity, and protective effective of inhaled COVID-19 vaccines: A systematic review and meta-analysis.

This study aimed to examine the safety, immunogenicity and protective effective of inhaled COVID-19 vaccines (ICVs). Literature research was done through EMBASE, Cochrane, PubMed, and Web of Science up to 10 March 2024. Pooled estimates with corresponding 95% confidence intervals (CI) were computed and compared using the random effects and common effects model. Of the 15 studies, 11 analyzed safety, 13 analyzed immunogenicity, and 3 analyzed protective effective. The results showed a favorable safety profile of ICVs for primary vaccination series, however it does not always seem to produce the expected immune response and protective effective. Meta-analysis of ICVs booster vaccinations (BVs) showed that the levels of neutralizing antibody Geometric mean titer (nAb-GMT) with aerosolised Ad5-nCoV (AAd5-nCoV) were all higher than those with inactivated vaccine (INA-nCoV) (standard mean difference (SMD) = 2.32; 95% CI: 1.96-2.69) and intramuscular Ad5-nCoV (IMAd5-nCoV) (SMD = 0.31; 95% CI: 0.14-0.48) against the original strain of SARS-CoV-2. Importantly, we also observed similar results in the omicron variant. In addition, ICV in BVs has high mucosal immunity to IgA antibodies. The risk of adverse events was comparable or lower for AAd5-nCoV compared to INA-nCoV or IMAd5-nCoV. Current evidence shows that the safety profile of ICVs were well. The booster dose of AAd5-nCoV had a high immune response (including mucosal immunity) and provided protection against COVID-19 caused by the SARS-CoV-2 omicron variant. Further studies are needed to investigate the long-term safety of intranasal vaccine booster protection and various types of ICVs.

Efficacy of adjuvant-associated COVID-19 vaccines against SARS-CoV-2 variants of concern in randomized controlled trials: A systematic review and meta-analysis.

BACKGROUND: Adjuvants may enhance the efficacy of vaccines. however, the efficacy of adjuvant-associated COVID-19 vaccines (ACVs) remains unclear since the emergence of the COVID-19 pandemic. This study aimed to address this gap by conducting a systematic review and meta-analysis of the efficacy of ACVs against Severe Acute Respiratory Syndrome Coronavirus 2 CoV (SARS-CoV-2) variants of concern (VOC). METHODS: A systematic search was conducted of randomized controlled trials (RCTs) evaluating the vaccine efficacy (VE) of ACVs against VOC (alpha, beta, gamma, delta, or Omicron), up to May 27, 2023. The DerSimonian-Laird random-effects model was used to assess VE with 95% confidence intervals (CI) through meta-analysis. Cochrane Risk of Bias tools were used to assess the risk of bias in RCTs. RESULTS: Eight RCTs with 113,202 participants were included in the analysis, which incorporated 4 ACVs [Matrix-M (NVX-CoV2373), Alum (BBV152), CpG-1018/Alum (SCB-2019), and AS03 (CoVLP]). The pooled efficacy of full vaccination with ACVs against VOC was 88.0% (95% CI: 83.0-91.5). Full vaccination was effective against Alpha, Beta, Delta, and Gamma variants, with VE values of 93.66% (95% CI: 86.5-100.74), 64.70% (95% CI: 41.87-87.54), 75.95% (95% CI: 67.9-83.99), and 91.26% (95% CI: 84.35-98.17), respectively. Currently, there is a lack of RCT evidence regarding the efficacy of ACVs against the Omicron variant. CONCLUSION: In this meta-analysis, it should be that full vaccination with ACVs has high efficacy against Alpha or Gamma variants and moderate efficacy against Beta and Delta variants. Notably, with the exception of the aluminum-adjuvanted vaccine, the other ACVs had moderate to high efficacy against the SARS-CoV-2 variant. This raises concerns about the effectiveness of ACVs booster vaccinations against Omicron.

Insights into serum metabolic biomarkers for early detection of incident diabetic kidney disease in Chinese patients with type 2 diabetes by random forest.

Diabetic kidney disease (DKD) is a leading cause of end-stage renal disease (ESRD) worldwide. Early detection is critical for the risk stratification and early intervention of progressive DKD. Serum creatinine (sCr) and urine output are used to assess kidney function, but these markers are limited by their delayed changes following kidney pathology, and lacking of both sensitivity and accuracy. Hence, it is essential to illustrate potential diagnostic indicators to enhance the precise prediction of early DKD. A total of 194 Chinese individuals include 30 healthy participants (Stage 0) and 164 incidents with type 2 diabetes (T2D) spanning from DKD's Stage 1a to 4 were recruited and their serums were subjected for untargeted metabolomic analysis. Random forest (RF), a machine learning approach, together with univariate linear regression (ULR) and multivariate linear regression (MvLR) analysis were applied to characterize the features of untargeted metabolites of DKD patients and to identify candidate DKD biomarkers. Our results indicate that 2-(α-D-mannopyranosyl)-L-tryptophan (ADT), succinyladenosine (SAdo), pseudouridine and N,N,N-trimethyl-L-alanyl-L-proline betaine (L-L-TMAP) were associated with the development of DKD, in particular, the latter three that were significantly elevated in Stage 2-4 T2D incidents. Each of the four metabolites in combination with sCr achieves better performance than sCr alone with area under the receiver operating characteristic curve (AUC) of 0.81-0.91 in predicting DKD stages. An average of 3.9 years follow-up study of another cohort including 106 Stage 2-3 patients suggested that "urinary albumin-to-creatinine ratio (UACR) + ADT + SAdo" can be utilized for better prognosis evaluation of early DKD (average AUC = 0.9502) than UACR without sexual difference.

Immunogenicity and safety of adjuvant-associated COVID-19 vaccines: A systematic review and meta-analysis of randomized controlled trials.

Background: The benefits and risks of adjuvant-associated COVID-19 vaccines (ACVs) are unclear. The study aimed to assess the immunogenicity and safety of ACVs compared with controls (placebo or the same vaccine without adjuvants [NACVs]). Methods: Randomized controlled trials sourced from PubMed, EMBASE, Web of Science, and Cochrane Library were systematically reviewed. Evaluators extracted information independently. The evidence quality was assessed using random-effects models. The risk of bias was assessed using the Cochrane Risk of Bias tool. Results: Of the 33 studies, 27 analyzed immunogenicity (n = 9069, ACVs group; n = 3757, control), and 26 analyzed safety (n = 58669, ACVs groups; n = 30733 control). Compared with controls, full vaccination with ACVs produced significant immune responses (relative risk [RR] of seroneutralization reaction, 12.3; 95 % confidence interval [95 % CI], 6.92-21.89; standardized mean deviation of geometric mean titer 3.96, 95 % CI, 3.35-4.58). Additionally, ACVs produced significant immunoreactivity compared with NACVs only (P < 0.05). Furthermore, full vaccination with ACVs significantly increased the risk of local and systemic adverse reactions (AEs) compared with controls. However, vaccination with ACVs did not significantly increase the risk of systemic and localized AEs compared with vaccination with NACVs only (P > 0.05). It was observed that ACVs had a lower risk of all-cause mortality than controls (RR, 0.51; 95 % CI 0.30-0.87). It was further found that ACVs produced nAb response against all sublines of the Omicron variant, but the antibody titers were lower than those for the SARS-CoV-2 original strain. Conclusions: The findings of this meta-analysis demonstrate that ACVs may have a superior effect and an acceptable safety in preventing COVID-19. Although these results suggest the potential of ACVs, further studies are required.

Immunogenicity and effectiveness of COVID-19 booster vaccination among people living with HIV: a systematic review and meta-analysis.

Background: The effect of booster vaccinations with the coronavirus virus disease (COVID-19) vaccine on people living with HIV (PLWH) remains unknown. In this study, we aimed to investigate the immunogenicity and effectiveness of booster doses of the COVID-19 vaccine in PLWH. Methods: Literature research was done through the PubMed, Embase, Cochrane Review, and Web of Science databases up to 4 July 2023. Pooled estimates were calculated and compared using the DerSimonian and Laird method for a random effects model. Randomized control trials and observational studies were both considered for inclusion. Results: We included 35 eligible studies covering 30,154 PLWH. The pooled immune response rate (IRR) of PLWH after the COVID-19 booster vaccination was 97.25% (95% confidence interval [CI], 93.81-99.49), and similar to healthy control (HC) (risk ratio [RR] = 0.98, 95% CI, 0.96-1.00). The pooled IRR for PLWH with CD4+ T-cell counts ≤ 200 was 86.27 (95% CI, 65.35-99.07). For Omicron variants, the pooled IRR for PLWH after booster dose was 74.07% (95% CI, 58.83-89.30), and the risk of IRR was reduced by 10% in PLWH compared with HC (RR = 0.90, 95% CI, 0.80-1.00). The T-cell immune response of PLWH was found to be comparable to HC (p ≥ 0.05). Subgroup analyses revealed that mRNA vaccines produced a relatively high IRR in PLWH compared to other vaccines. In addition, the results showed that booster vaccination appeared to further reduce the risk of COVID-19-related infections, hospitalizations, and deaths compared with the primary vaccination. Conclusion: It was shown that booster vaccination with the COVID-19 vaccine provided a high IRR in PLWH and still produced a desirable moderate IRR in PLWH with a CD4+ T-cell count of ≤ 200. Importantly, the humoral and T-cell responses to booster vaccination in PLWH were comparable to HC, and similar results were observed with the SARS-CoV-2 Omicron variant. Our review strongly emphasizes the effect of mRNA vaccine booster vaccination in PLWH on eliciting desirable protective IRR. Furthermore, booster vaccination appears to further reduce the risk of COVID-19 infection, hospitalization, and death in PLWH compared to primary vaccination. However, more evidence is needed to confirm its effectiveness.

Derivative of cinnamic acid inhibits T3SS of Xanthomonas oryzae pv. oryzae through the HrpG-HrpX regulatory cascade.

Bacterial leaf blight (BLB) caused by Xanthomonas oryzae pv. oryzae (Xoo) has a significant impact on rice yield and quality worldwide. Traditionally, bactericide application has been commonly used to control this devastating disease. However, the overuse of fungicides has led to a number of problems such as the development of resistance and environmental pollution. Therefore, the development of new methods and approaches for disease control are still urgent. In this paper, a series of cinnamic acid derivatives were designed and synthesized, and three novel T3SS inhibitors A10, A12 and A20 were discovered. Novel T3SS inhibitors A10, A12 and A20 significantly inhibited the hpa1 promoter activity without affecting Xoo growth. Further studies revealed that the title compounds A10, A12 and A20 significantly impaired hypersensitivity in non-host plant tobacco leaves, while applications on rice significantly reduced symptoms of bacterial leaf blight. RT-PCR showed that compound A20 inhibited the expression of T3SS-related genes. In summary, this work exemplifies the potential of the title compound as an inhibitor of T3SS and its efficacy in the control of bacterial leaf blight.

Elemene induces cell apoptosis via inhibiting glutathione synthesis in lung adenocarcinoma.

ETHNOPHARMACOLOGICAL RELEVANCE: The rhizome of Curcuma wenyujin Y.H. Chen & C. Ling, also known as Wen-E-Zhu, has been used for cancer treatment since ancient times, with roots dating back to the Song Dynasty. Elemene (EE), a sesquiterpene extract with potent anticancer properties, is extracted from Wen-E-Zhu, with ß-elemene (BE) being its main active compound, along with trace amounts of ß-caryophyllene (BC), γ-elemene and δ-elemene isomers. EE has demonstrated broad-spectrum anti-cancer effects and is commonly used in clinical treatments for various types of malignant cancers, including lung cancer. Studies have shown that EE can arrest the cell cycle, inhibit cancer cell proliferation, and induce apoptosis and autophagy. However, the exact mechanism of its anti-lung cancer activity remains unclear and requires further research and investigation. AIM OF THE STUDY: In this study, the possible mechanism of EE and its main active components, BE and BC, against lung adenocarcinoma was investigated by using A549 and PC9 cell lines. MATERIALS AND METHODS: The subcutaneous tumor model of nude mice was constructed to evaluate the efficacy of EE in vivo, then the in vitro half-inhibitory concentration (IC50) of EE and its main active components, BE and BC, on A549 and PC9 cells at different concentrations were determined by CCK-8. Flow cytometry was used to detect the apoptosis and cycle of A549 and PC9 cells treated with different concentrations of BE and BC for 24 h. Non-targeted metabolomics analysis was performed on A549 cells to explore potential target pathways, which were subsequently verified through kit detection and western blot analysis. RESULTS: Injection of EE in A549 tumor-bearing mice effectively suppressed cancer growth in vivo. The IC50 of EE and its main active components, BE and BC, was around 60 µg/mL. Flow cytometry analysis showed that BE and BC blocked the G2/M and S phases of lung adenocarcinoma cells and induced apoptosis, leading to a significant reduction in mitochondrial membrane potential (MMP). Results from non-targeted metabolomics analysis indicated that the glutathione metabolism pathway in A549 cells was altered after treatment with the active components. Kit detection revealed a decrease in glutathione (GSH) levels and an increase in the levels of oxidized glutathione (GSSG) and reactive oxygen (ROS). Supplementation of GSH reduced the inhibitory activity of the active components on lung cancer and also decreased the ROS content of cells. Analysis of glutathione synthesis-related proteins showed a decrease in the expression of glutaminase, cystine/glutamate reverse transporter (SLC7A11), and glutathione synthase (GS), while the expression of glutamate cysteine ligase modified subunit (GCLM) was increased. In the apoptosis-related pathway, Bax protein and cleaved caspase-9/caspase-9 ratio were up-regulated and Bcl-2 protein was down-regulated. CONCLUSIONS: EE, BE, and BC showed significant inhibitory effects on the growth of lung adenocarcinoma cells, and the mechanism of action was linked to the glutathione system. By down-regulating the expression of proteins related to GSH synthesis, EE and its main active components BE and BC disrupted the cellular redox system and thereby promoted cell apoptosis.

Anti-tumour and radiosensitising effects of PARP inhibitor on cervical cancer xenografts.

This study evaluated the radiosensitising effect of niraparib; a poly(adenosine diphosphate-ribose) polymerase (PARP) inhibitor on HeLa cervical cancer cells in nude mice and explored its possible mechanism. Twenty-four 3-5-week-old female BALB/c nude mice, inoculated with HeLa cells into the right hind leg, were randomly assigned into eight groups with three mice per group and treated. The tumour volume was significantly reduced under niraparib + radiotherapy combination as compared to monotherapy and untreated mice. The tumour growth was significantly delayed by 23.33-39 days when treated with combination therapy (p<.05). Further, univariate analysis revealed prolonged time for tumour growth when radiotherapy was followed by niraparib (I.G.) rather than niraparib (I.P.) (p=.003). Combination therapy reduced levels of PARP-1 precursor, PARP-1 splicer, PAR and RAD51 protein with high expression of γ-H2AX/CC3 and low expression of Ki-67. Niraparib in combination with radiotherapy can enhance the formation of DNA double strand breaks in HeLa cells and up regulate the expression of γ-H2AX/CC3.IMPACT STATEMENTWhat is already known on this subject? Asia has the highest incidence of cervical cancer (58.2%). Poly(adenosine diphosphate-ribose) polymerases (PARPs) are family of enzymes involved in single-strand break (SSB) and double-strand break (DSB) repair pathways. Niraparib is an effective inhibitor of both PARP-1 and PARP-2 and has the ability to cross the blood-brain barrier.What the results of this study add? Our study demonstrated that the combination of niraparib and radiotherapy can significantly enhance the cytotoxicity induced by radiotherapy. The inhibition effect of radiotherapy combined with niraparib on the tumour growth of mice was prominent, thereby establishing the radio-sensitisation activity of niraparib.What are the implications of these findings for clinical practice and/or further research? Niraparib can improve the cytotoxic effect of radiotherapy by increasing the formation of DSBs and up regulating the expression of apoptotic protein in HeLa cells.

Relative effectiveness of bivalent COVID-19 vaccine: a systematic review and meta-analysis.

Objective: The rapid development of COVID-19 bivalent vaccines (BVs) has encompassed both the original virus strains and the variant strain. However, the effectiveness of BVs is largely unknown. Therefore, we conducted a systematic review and meta-analysis of the effectiveness of BVs. Methods: Literature research was conducted through PubMed, Cochrane Library, Embase, and Web of Science up until November 4, 2023. Both randomized control trials and observational studies were considered for inclusion. Pooled estimates were calculated using a random effects model. The Newcastle-Ottawa Scale (NOS) was used to assess the risk of bias in cohort and case-control studies. Results: A total of 1,174 articles were reviewed and 22 eligible studies were included. All included studies were observational (15 cohort studies, 7 case-control studies). The total number of participants was 39,673,160, and the number of people vaccinated with BVs as an intervention group was 11,585,182. Two mRNA BVs were mainly involved, including the ancestral strain and the BA.1 or BA.4-5 variants. Meta-analysis results showed, compared with the monovalent vaccines (MVs), the relative effectiveness (rVE) of the BVs in COVID-19-associated infections/symptomatic infections, illnesses, hospitalizations, and deaths was 30.90% [95% confidence interval (CI), 8.43-53.37], 39.83% (95% CI, 27.34-52.32), 59.70% (95% CI, 44.08-75.32), and 72.23% (95% CI, 62.08-82.38), respectively. For those aged 50 years and older, BVs provided an additional 49.69% (95% CI, 41.44-57.94) effective protection compared with MVs. During the dominance period of the omicron XBB variant strain, BVs provided an additional 47.63% (95% CI, 27.45-67.82) effective protection compared with MVs. Conclusion: Our findings show that the rVE of BVs in preventing COVID-19-associated infections, symptomatic infections, illnesses, hospitalizations, and deaths is higher compared to MVs. Particularly for people over 50 years of age and during the Omicron variant XBB dominance phase, BVs provided superior protection. Therefore, BVs may have a broader application in the prevention and control of coronaviruses variant.

Research progress on the relationship between social isolation and cognitive ability in the elderly / 中华老年医学杂志

Social isolation represents the development of a certain level, either partial or complete, of deprivation of socialization and may have adverse effects in many aspects for the elderly, which can be physiological, psychological and social.Meanwhile, during the course of human life, aging becomes an inevitable process and brings about changes in cognitive ability, which become an important focus of our attention.This paper reviews the research progress on the relationship between social isolation and cognitive ability in the elderly, in order to provide a new perspective for future research on social isolation and cognitive ability in the elderly and also to offer new insight on how to construct a model of intervention and health management for the elderly population with social isolation.

The assessment value of endothelial glycocalyx degradation products in pulmonary edema patients with acute respiratory distress syndrome / 中华急诊医学杂志

Objective:To investigate the application of endothelial glycocalyx degradation products in assessing the severity of pulmonary edema in patients with acute respiratory distress syndrome (ARDS).Methods:A prospective study was conducted to select patients diagnosed with ARDS at Wuxi People's Hospital from July 1, 2018 to December 31, 2019. The extravascular lung water index (EVLWI) was recorded within 2 h after admission by continuous cardiac output with pulse indicator. The indexes of glycocalyx degradation products syndecan-1 (SDC-1), heparan sulfate (HS), hyaluronic acid (HA) and the concentrations of inflammatory factors [blood tumor necrosis factor α (TNF-α), interleukin (IL)-6 and IL-10] were measured by enzyme-linked immunosorbent assay. Pearson correlation method was adopted to analyze the correlation of glycocalyx degradation products with EVLWI and inflammatory factors in ARDS patients. The patients were divided into the mild pulmonary edema group and severe pulmonary edema group according to EVLWI at the cut-off value of 10 mL/kg, and the differences of glycocalyx degradation products and inflammatory factors between the two groups were compared. Receiver operating characteristic (ROC) curve of the subjects were plotted to analyze the value of glycocalyx degradation products in determining the severity of pulmonary edema.Results:A total of 85 ARDS patients were enrolled. Pearson correlation analysis showed that SDC-1, HS, and HA were all positively correlated with IL-6, TNF-α, EVLWI (all P<0.05), but did not correlate with IL-10 (all P>0.05). Comparison of indicators between the mild pulmonary edema group (39 cases) and the severe pulmonary edema group (46 cases) showed that: IL-6[(33.63±3.43) ng/L vs. (39.99±4.64) ng/L], TNF-α[(43.38±6.05) ng/L vs. (50.79±7.35) ng/L], SDC-1[(494.13±47.23) ng/L vs. (563.50±56.36) ng/L], HS[(114.02±18.39) ng/mL vs. (138.93±17.02) ng/mL], and HA[(441.44±62.52) ng/mL vs. (546.23±85.24) ng/mL] were statistically different between the two groups(all P<0.05). Whereas, IL-10 [(24.37±10.11) ng/L vs. (28.75±11.98) ng/L] was not statistically different between the two groups ( P>0.05). ROC curve analysis showed that the combined prediction of SDC-1, HA and HS indicators was superior to the single indicator. The area under the ROC curve combining the three indicators was 0.928 (95% CI: 0.872-1.000), with a sensitivity and specificity of 87.5% and 86.7%, respectively. Conclusions:There is a positive correlation between glycocalyx degradation products SDC-1, HS, HA and EVLWI in ARDS patients. The application of these three glycocalyx degradation products can be used as a reliable indicators for judging the severity of pulmonary edema in ARDS patients.

Cloning and expression analysis of ANR genes from different species of Lonicera japonica Thunb / 药学学报

Anthocyanidin reductase (ANR) is one of the key enzyme in the flavonoid biosynthetic pathway, and its catalytic activity is important for the synthesis of plant anthocyanin. In this study, specific primers were designed according to the transcriptome data of Lonicera japonica Thunb., and the CDS, gDNA and promoter sequences of ANR genes from Lonicera japonica Thunb. and Lonicera japonica Thunb. var. chinensis (Wats.) Bak. were cloned. The results showed that the CDS sequences of LjANR and rLjANR were 1 002 bp, the gDNA sequences were 2 017 and 2 026 bp respectively, and the promoter sequences were 1 170 and 1 164 bp respectively. LjANR and rLjANR both contain 6 exons and 5 introns, which have the same length of exons and large differences in introns. The promoter sequences both contain a large number of light response, hormone response and abiotic stress response elements. Bioinformatics analysis showed that both LjANR and rLjANR encoded 333 amino acids and were predicted to be stable hydrophobic proteins without transmembrane segments and signal peptides. The secondary structures of LjANR and rLjANR were predicted to be mainly consisted of α-helix and random coil. Sequence alignment and phylogenetic analysis showed that LjANR and rLjANR had high homology with Actinidia chinensis var. chinensis, Camellia sinensis and Camellia oleifera, and were closely related to them. The expression levels of LjANR and rLjANR were the highest in flower buds and the lowest in roots. The expression patterns at different flowering stages were similar, with higher expression levels in S1 and S2 stages and then gradually decreased until reaching the lowest level in S4 stage, after a slow increase in S5 stage, the expression levels decreased again. The expression levels of ANR genes in the two varieties showed significant differences in roots, S2 and S5 stages, while the differences in stems, flower buds, S1, S3 and S6 stages were extremely significant. The prokaryotic expression vector pET-32a-LjANR was constructed for protein expression. The target protein was successfully expressed of about 59 kD. This study lays a foundation for further study on the function of ANR gene and provides theoretical guidance for breeding new varieties of Lonicera japonica Thunb.

Evaluation of the physicochemical properties of alkali-soluble polysaccharide from Poria and its application in diclofenac sodium sustained-release tablets / 药学学报

In this study, alkali-soluble polysaccharide was extracted from Poria residue, and the structure of alkali-soluble polysaccharide was characterized by Fourier transform infrared spectroscopy (FTIR), X-ray powder diffraction (XRD), and differential scanning calorimetry (DSC). The physical morphology of alkali-soluble polysaccharide and ethyl cellulose (EC) was investigated by scanning electron microscopy (SEM), and the focus on angle of repose, bulk density, tapped density, Carr index, interparticle porosity, cohesion index, Hausner ratio, etc. The physical fingerprints were drawn, and the powder properties were evaluated by multivariate analysis. Diclofenac sodium extended-release tablets were prepared by direct compression method using alkali-soluble polysaccharide and EC as insoluble backbone materials to evaluate the basic properties of the extended-release tablets, investigate the in vitro drug release behavior and study the release mechanism. The results showed that alkali-soluble polysaccharide is a semi-crystalline polymer with smooth lamellar structure, and its stacking and compressibility are stronger than EC. The in vitro release experiments showed that the slow release performance of alkali-soluble polysaccharide is stronger than EC, and the release behavior of the prepared slow release tablets is in accordance with the Higuchi model. The pore structure is formed inside the tablets during the release process, and the release mode is pore diffusion release. The results of this study are of great significance for the development of new slow-release materials and the rational use of resources.

Research Progress on Association of Dietary Fat and Fatty Acid Intake with Prognosis of Ovarian Cancer / 肿瘤防治研究

Ovarian cancer is characterized by insidious onset and poor prognosis, and among gynecological malignancies, its mortality rate ranks first, which poses a serious threat to women's health worldwide. In recent years, increasing evidence has suggested that modifiable lifestyle factors, particularly dietary factors, played important roles in the prognosis of ovarian cancer. As important nutrients, dietary fats and fatty acids can affect various vital physiological functions in human beings. However, the association of dietary fat and fatty acid intake with the prognosis of ovarian cancer remains unclear. Therefore, this review aims to analyze the existing epidemiological evidence between the two variables by searching the literature to provide dietary suggestions for ovarian cancer patients.

Drug-induced hypersensitivity syndrome with high procalcitonin levels due to piperacillin/tazobactam and meropenem: A case report.

Drug reaction with eosinophilia and systemic symptoms (DRESS) is a rare and life-threatening adverse drug reaction. It is characterized by a long latency period with rash, hematological abnormalities, and visceral damage. Clinical manifestations of DRESS vary. Thus, accurate clinical diagnosis and identification are essential to ensure timely treatment commencement for improving prognosis and speeding up recovery. We report the case of a 66-year-old male patient with a drug reaction induced by a beta-lactam antibiotic, piperacillin/tazobactam (Pip/Taz). This resulted in the manifestation of both eosinophilic and systemic symptoms. Ten days after the Pip/Taz treatment commencement, the patient developed hyperthermia and elevated serum procalcitonin (PCT), leading to a misdiagnosis of an exacerbated infection. Meropenem treatment was then started. However, after 72 h, the patient developed a generalized rash, eosinophilia, hematological abnormalities, and visceral damage. Moreover, PCT levels were significantly elevated. All these symptoms were associated with DRESS. The sensitizing drug was discontinued, and glucocorticoids were administered, resulting in gradual subsiding of symptoms and decreases in serum PCT levels. Clinicians should be aware that elevated PCT serum levels may be a diagnostic biomarker for DRESS, which requires specific treatment. Furthermore, studies are warranted to further evaluate and elucidate the role of PCT in response to DRESS.

Usefulness of AFP, PIVKA-II, and Their Combination in Diagnosing Hepatocellular Carcinoma Based on Upconversion Luminescence Immunochromatography.

OBJECTIVES: To evaluate the prognostic values of serum PIVKA-II (prothrombin induced by vitamin K absence-II) and α-fetoprotein (AFP) and the combination of these analytes for identifying hepatocellular carcinoma (HCC), and to analyze the correlation between biomarkers and clinicopathological features of HCC. METHODS: The levels of PIVKA-II and AFP in 331 case individuals were determined by upconverting phosphor technology-based immune lateral flow (UPT-LF) assay. We used the ROC curve to determine the diagnostic value; the relationships between the biomarkers and clinicopathological features of HCC also were analyzed. RESULTS: AFP and PIVKA-II have good diagnostic performance in the diagnosis of HCC; the best AUC was 0.76, 0.74. High levels of PIVKA-II were more advantageous than AFP in predicting tumor size, portal-vein embolism, and vascular invasion (all P <.05). CONCLUSION: Levels of PIVKA-II and AFP showed good diagnostic value for HCC, but the level of PIVKA-II was more closely related to the clinicopathological features of HCC.

The influence of bacterial outer membrane vesicles tumor vaccine on tumor cell proliferation and CD8 + T cell infiltration of mouse with pancreatic cancer / 中华消化外科杂志

Objective:To investigate the influence of bacterial outer membrane vesicles (OMVs) tumor vaccine on tumor cell proliferation and CD8 + T cell infiltration of mouse with pancreatic cancer. Methods:The experimental study was conducted. The ovalbumin (OVA) lentivirus vector plasmid pLV-EF1a-hluc-P2A-mNeongreen-CMV-OVA-3Xflag-P2A-puro was used to construct the mouse pancreatic cancer Pan02-OVA cells. The ClyA-Catchers-OMVs (CC-OMVs) originated from Escherichia coli and labeled antigenic peptide SpyTag-OVA were used to construct the OMVs tumor vaccine. Mouse CD8 + T cells were stimulated by OMVs tumor vaccine, and the effects of OMVs tumor vaccine on inhibiting pancreatic cancer cells proliferation and stimulating CD8 + T cell infiltration were analy-zed by in vitro cell killing assay, including the OMVs tumor vaccine stimulated T cell group and the control T cell group, subcutaneous pancreatic cancer model, including the OMVs tumor vaccine group and the control group, and immunohistochemical staining. Observation indicators: (1) identification of mouse pancreatic cancer Pan02-OVA cells; (2) morphological observation of CC-OMVs; (3) inhibi-tion of mouse pancreatic cancer Pan02-OVA cells by OMVs tumor vaccine specific T cells; (4) inhibi-tion of mouse pancreatic cancer by OMVs tumor vaccine; (5) CD8 + T cell infiltration in pancreatic cancer tissue of mouse stimulated by OMVs tumor vaccine. Measurement data with normal distribu-tion were represented as Mean± SD, and comparison between groups was analyzed using the t test. Count data were described as absolute numbers or percentages. Results:(1) Identification of mouse pancreatic cancer Pan02-OVA cells. Results of laser scanning confocal microscopy showed that the mNeongreen fluorescence was expressed in Pan02-OVA cells infected with the OVA lentivirus vector plasmid of pLV-EF1a-hluc-P2A-mNeongreen-CMV-OVA-3Xflag-P2A-puro. Results of Flow cytometry showed that using the mouse pancreatic cancer Pan02 cells as references, the protein expression rate of Flag on the Pan02-OVA cells was 90.7%. (2) Morphological observation of CC-OMVs. Results of transmission electron microscopy analysis showed that the CC-OMVs were in spherical shape, with a diameter <50 nm. (3) Inhibition of mouse pancreatic cancer Pan02-OVA cells by OMVs tumor vaccine specific T cells. Results of cell proliferation toxicity test showed that the absorbance at 450 nm of mouse pancreatic cancer Pan02-OVA cells was 0.41±0.12 and 1.05±0.15 in the OMVs tumor vaccine-stimulated T cell group and the control T cell group, respectively, showing a significant difference between the two groups ( t=9.54, P<0.05). (4) Inhibition of mouse pancreatic cancer by OMVs tumor vaccine. The weight of subcutaneous tumor tissue in the back of mouse was (81±10)g and (153±17)g in the OMVs tumor vaccine group and the control group, respectively, showing a significant difference between the two groups ( t=8.26, P<0.05). (5) CD8 + T cell infiltration in pancreatic cancer tissue of mouse stimulated by OMVs tumor vaccine. Results of immuno-histochemical staining showed that the numbers of CD8 + T cells staining in the mouse back subcu-taneous tumor tissues was 28.7±3.5 and 9.3±1.5 in the OMVs tumor vaccine group and the control group, respectively, showing a significant difference between the two groups ( t=8.74, P<0.05). Conclusion:Bacterial OMVs tumor vaccine can inhibit proliferation of pancreatic cancer cells and increase the numbers of CD8 + T cells infiltrated in pancreatic cancer tissue of mouse.

Long-term follow-up results of radiotherapy combined with transcatheter arterial chemoembolization and tyrosine kinase inhibitor in patients with hepatocellular carcinoma showing macrovascular invasion / 中华放射医学与防护杂志

Objective:To assess the long-term follow-up results of intensity-modulated radiotherapy (IMRT) combined with transcatheter arterial chemoembolization (TACE) and tyrosine kinase inhibitor (TKI) in patients with hepatocellular carcinoma (HCC) showing macrovascular invasion (MVI).Methods:A retrospective analysis was conducted for 63 patients with HCC showing MVI without distant metastasis treated in Peking University Cancer Hospital from October 2015 to October 2018. Among them 28 patients were treated with IMRT combined with TACE and sorafenib (Group A) and 35 patients were treated with IMRT combined with TACE (Group B). Propensity score matching (PSM) was applied to assess the progression-free survival (PFS) and the overall survival (OS) of both groups.Results:The median follow-up time was 62 months. Before PSM, the median OS of group A and B were 19.0 months and 15.2 months ( χ2=3.15, P=0.076), respectively, and the median PFS of groups A (10.7 months) was longer than that of group B (8.6 months; χ2=3.99, P=0.046). After PSM, the median OS of group A (30.6 months) was significantly longer than that of group B (15.2 months; χ2=5.34, P=0.023), and the PFS of groups A (12.5 months) was still longer than that of group B (8.3 months; χ2=4.79, P=0.026). In the whole group, 10 patients (15.9%) suffered from grade-3 hematologic toxicity, and seven patients (11.1%) experienced grade-3 hepatic toxicity. The incidence of skin reactions, hand-foot syndrome, and diarrhea in group A was higher than that in group B, but all these adverse events were grade 1-2. Moreover, no grade-4 adverse events, radiation-induced liver disease, and treatment-related mortality occurred in both groups. Conclusions:As demonstrated by the long-term follow-up result, IMRT combined with TACE and TKI could improve both the PFS and the OS of patients with HCC showing MVI after PSM.

New eudesmane sesquiterpenoids from Atractylodis Macrocephalae Rhizoma and their inhibitory activities against SREBPs / 中国中药杂志

Three sesquiterpenoids were isolated and purified from the 95% ethanol extract of Atractylodis Macrocephalae Rhizoma by column chromatography on silica gel, Sephadex LH-20, ODS, and high-performance liquid chromatography(HPLC). Their chemical structures were identified on the basis of spectroscopic analysis and physiochemical properties as(7Z)-8β,13-diacetoxy-eudesma-4(15),7(11)-diene(1), 7-oxo-7,8-secoeudesma-4(15),11-dien-8-oic acid(2), and guai-10(14)-en-11-ol(3). Compounds 1 and 2 are new compounds and compound 3 was obtained from Compositae family for the first time. Compounds 1, 2, and 3 showed weak inhibitory activities against sterol regulatory element-binding proteins(SREBPs).

N-terminal truncation of prenyltransferase enhances the biosynthesis of prenylnaringenin / 生物工程学报

8-prenylnaringenin (8-PN) is a potent estrogen with high medicinal values. It also serves as an important precursor for many prenylated flavonoids. Microbial synthesis of 8-PN is mainly hindered by the low catalytic activity of prenyltransferases (PTS) and insufficient supply of precursors. In this work, a SfN8DT-1 from Sophora flavescens was used to improve the efficiency of (2S)-naringenin prenylation. The predicted structure of SfN8DT-1 showed that its main body is comprised of 9 α-helices and 8 loops, along with a long side chain formed by nearly 120 amino acids. SfN8DT-1 mutants with different side-chain truncated were tested in Saccharomyces cerevisiae. A mutant expressing the truncated enzyme at K62 site, designated as SfND8T-1-t62, produced the highest 8-PN titer. Molecular docking of SfN8DT-1-t62 with (2S)-naringenin and dimethylallyl diphosphate (DMAPP) showed that K185 was a potentially crucial residue. Alanine scanning within a range of 0.5 nm around these two substrates showed that the mutant K185A may decrease its affinity to substrates, which also indicated K185 was a potentially critical residue. Besides, the mutant K185W enhanced the affinity to ligands implied by the simulated saturation mutation, while the saturated mutation of K185 showed a great decrease in 8-PN production, indicating K185 is vital for the activity of SfN8DT-1. Subsequently, overexpressing the key genes of Mevalonate (MVA) pathway further improved the titer of 8-PN to 31.31 mg/L, which indicated that DMAPP supply is also a limiting factor for 8-PN synthesis. Finally, 44.92 mg/L of 8-PN was produced in a 5 L bioreactor after 120 h, which is the highest 8-PN titer reported to date.