Objective:To explore the application of COVID-19-specific IgG antibody in identifying epidemic Omicron BA.5 strain infection.Method:Omicron BF.7/BA.5 naturally infected population, healthy population vaccinated with the COVID-19 vaccine, and Omicron BF.7/BA.5 breakthrough cases were enrolled into this study. The serum WT-S-IgG and BA.5-S-IgG were detected by indirect ELISA, and the serum-specific IgG antibody levels of different populations were compared. The application value of the two antibody titers and the ratio of the two antibodies in identifying Omicron BA.5 epidemic strain infection were explored by the ROC curve, aiming to provide technical support for pathogen diagnosis.Results:The antibody titers of WT-S-IgG and BA.5-S-IgG in the breakthrough cases were higher than those in the naturally infected population and the healthy population ( P<0.05). The area under the curve (AUC) of WT-S-IgG and BA.5-S-IgG in identifying epidemic Omicron BA.5 strain infection was 0.947 and 0.961, respectively. The AUC of BA.5-S-IgG and WT-S-IgG antibody titer ratio was 0.873. When the antibody titer ratio was 0.855, the sensitivity and specificity were 80.00% and 90.00%, respectively. According to the interval since the last infection, the AUC of the ratio of BA.5-S-IgG to WT-S-IgG antibody titer to identify the infection of epidemic strains less than 30 days and more than 30 days was 0.887 and 0.863, respectively, and the sensitivity and specificity were both above 80%. Conclusion:Both BA.5-S-IgG and WT-S-IgG, as well as the combination of these two antibodies, are of high value in the identification of epidemic strains.

Objective:To explore the application of COVID-19-specific IgG antibody in identifying epidemic Omicron BA.5 strain infection.Method:Omicron BF.7/BA.5 naturally infected population, healthy population vaccinated with the COVID-19 vaccine, and Omicron BF.7/BA.5 breakthrough cases were enrolled into this study. The serum WT-S-IgG and BA.5-S-IgG were detected by indirect ELISA, and the serum-specific IgG antibody levels of different populations were compared. The application value of the two antibody titers and the ratio of the two antibodies in identifying Omicron BA.5 epidemic strain infection were explored by the ROC curve, aiming to provide technical support for pathogen diagnosis.Results:The antibody titers of WT-S-IgG and BA.5-S-IgG in the breakthrough cases were higher than those in the naturally infected population and the healthy population ( P<0.05). The area under the curve (AUC) of WT-S-IgG and BA.5-S-IgG in identifying epidemic Omicron BA.5 strain infection was 0.947 and 0.961, respectively. The AUC of BA.5-S-IgG and WT-S-IgG antibody titer ratio was 0.873. When the antibody titer ratio was 0.855, the sensitivity and specificity were 80.00% and 90.00%, respectively. According to the interval since the last infection, the AUC of the ratio of BA.5-S-IgG to WT-S-IgG antibody titer to identify the infection of epidemic strains less than 30 days and more than 30 days was 0.887 and 0.863, respectively, and the sensitivity and specificity were both above 80%. Conclusion:Both BA.5-S-IgG and WT-S-IgG, as well as the combination of these two antibodies, are of high value in the identification of epidemic strains.

Hypoxia-inducible factor(HIF)are a family of molecules that are critical for regulating cellular adaptation to hy-poxia,which can be activated by hypoxia and other stimuli,and then translocated into nucleus,where they modulate the transcription of target genes.Under the pathological conditions,such as inflammation and tumor,tissue microenvironment is often hypoxic.Innate lymphoid cells(ILCs)and T lymphocytes serve as important effector cells in defense against infection and tumor,and their functions are regulated by HIF proteins.In recent years,increasing evidence highlights the importance of HIF1α and HIF2α,two members of the HIF family,in regulating ILCs and T cells,providing new insights into mechanisms and treatment of diseases.This review summa-rizes the research progress on the role of HIF family proteins in ILCs and T cells and the underlying mechanisms.

Purpose: Oligometastatic non–small cell lung cancer (NSCLC) patients have been increasingly regarded as a distinct group that could benefit from local treatment to achieve a better clinical outcome. However, current definitions of oligometastasis are solely numerical, which are imprecise because of ignoring the biological heterogeneity caused by genomic characteristics. Our study aimed to profile the molecular alterations of oligometastatic NSCLC and elucidate its potential difference from polymetastasis. Materials and Methods: We performed next-generation sequencing to analyze tumors and paired peripheral blood from 77 oligometastatic and 21 polymetastatic NSCLC patients to reveal their genomic characteristics and assess the genetic heterogeneity. Results: We found ERBB2, ALK, MLL4, PIK3CB, and TOP2A were mutated at a significantly lower frequency in oligometastasis compared with polymetastasis. EGFR and KEAP1 alterations were mutually exclusive in oligometastatic group. More importantly, oligometastasis has a unique significant enrichment of apoptosis signaling pathway. In contrast to polymetastasis, a highly enriched COSMIC signature 4 and a special mutational process, COSMIC signature 14, were observed in the oligometastatic cohort. According to OncoKB database, 74.03% of oligometastatic NSCLC patients harbored at least one actionable alteration. The median tumor mutation burden of oligometastasis was 5.00 mutations/Mb, which was significantly associated with smoking, DNA damage repair genes, TP53 mutation, SMARCA4 mutation, LRP1B mutation, ABL1 mutation. Conclusion Our results shall help redefine oligometastasis beyond simple lesion enumeration that will ultimately improve the selection of patients with real oligometastatic state and optimize personalized cancer therapy for oligometastatic NSCLC.

Objective:To investigate the diagnostic and prognostic value of D-dimer level in patients with hepatitis B-related acute-on-chronic liver failure (HBV-ACLF).Methods:A total of 142 cases diagnosed with ACLF were randomly selected as research objects in the open cohort using the Chinese Group on the Study of Severe Hepatitis B-ACLF (COSSH-ACLF). Plasma D-dimer levels were compared between patients with ACLF and non-ACLF and patients with different ACLF grades. Survival and death group D-dimer levels were compared with the end points of 28 days and 90 days, respectively. The correlation between D-dimer and other laboratory indicators and prognostic scores were investigated. Area under receiver operating characteristic curve (AUROC) was used to evaluate the D-dimer value for predicting the prognosis of ACLF patients. 125 external ACLF cases were used for validation. A Student t test or Mann-Whitney U test was used to compare continuous measurement data between two groups. Kruskal-Wallis test was used to compare continuous measurement data between multiple groups.Results:Plasma D-dimer levels in the ACLF [2 588.5 (1 142.8, 5 472.8) μg/L] ] and non-ACLF group [1 385.5 (612.0, 3 840.3) μg/L] had a significant difference ( P<0.001). ACLF-3 patients had significantly higher D-dimer levels than ACLF-1/2 patients (ACLF-3 vs. ACLF-1, P<0.001; ACLF-3 vs. ACLF-2, P<0.05). Patients who died at 28/90 days had significantly higher D-dimer levels than those whom survived ( P<0.001). There was a significant positive correlation between D-dimer level with prothrombin time (PT), international normalized ratio (INR), high-density lipoprotein C, as well as various prognostic scores (COSSH-ACLFs, CLIF-C ACLFs, CLIF-OFs, MELDs). AUROC of D-dimer in predicting the prognosis of ACLF patients at 28 days and 90 days was 0.751 (95% CI: 0.649-0.852) and 0.787 (95% CI: 0.695-0.878), respectively, which did not differ significantly compared with the predictive ability of other scores ( P<0.05), and similar results were confirmed by an external validation group of 125 cases. Conclusion:D-dimer level is significantly higher in patients with ACLF, so it is an independent predictor of prognosis at 28 and 90 days.

Objective:To evaluate the value of the crescent sign for predicting the invasiveness of lung adenocarcinoma presenting as pure ground-glass nodule (pGGN).Methods:The clinical, pathological and imaging data of 316 patients (320 pGGNs) confirmed lung adenocarcinoma by surgery and pathology from July 2013 to June 2018 in the First Affiliated Hospital of Wenzhou Medical University were retrospectively analyzed. All pGGNs were divided into preinvasive group (148 pGGNs) and invasive group (172 pGGNs) according to histopathology. Logistic regression analysis was used to determine the risk factors for invasiveness of pGGN, and the ROC curve analysis was performed on each risk factor.Results:Crescent sign was found in 24 cases (16.2%) in the preinvasive group and 49 (28.5%) in the invasive group, and the difference between the two groups was statistically significant (χ2=6.804 ,P=0.009).There were statistically significant differences in patient′s age, lesion size, shape, lobulation sign, and vascular stretch sign between the two groups ( P<0.05). The ROC curve showed that with the lesion size 10.5 mm as the optimal cut off value, the sensitivity for differential diagnosis of preinvasive and invasive lesions was 65.7%, the specificity was 61.5%, and the area under the curve was 0.666. Logistic regression analysis showed that maximum diameter of the lesion ≥10.5 mm, irregular shape, crescent sign and vascular stretch were independent risk factors of invasiveness of pGGN, and the OR value (95%CI) were 3.192 (1.981-5.144), 3.672 (1.545-8.725), 1.972 (1.104-3.521), and 2.026 (1.087-3.777), respectively. A logistic model was established based on the above four independent risk factors, and the area under curve was 0.711 (95%CI 0.655-0.768). Conclusion:Crescent sign can effectively reflect the invasiveness of pGGN. Maximum diameter of the lesion ≥10.5 mm, irregular shape, crescent sign and vascular stretch sign are independent risk factors of invasiveness of pGGN.

Objective:To explore the molecular mechanism of paraquat (PQ)-induced lung injuries.Methods:Male C57BL/6 mice aged 6 to 8 weeks were randomly divided into four groups. Mice in the experimental groups (three groups, nine rats in each group) were intraperitoneally injected with 40 mg/kg PQ to establish an infection model, and mice in the control group ( n=9) were intraperitoneally injected with the same dose of saline. Mice were sacrificed at day 2, 7 and 14 after PQ administration. Pathological changes of lung tissues from mice model were observed by Hematoxylin-eosin staining. The expression of different proteins in the lung tissues at different time points were detected and identified by tandem mass spectrometry tag technology (TMT), and the functional analysis was performed. Results:Compared with the control group, there were 91 (69 up and 22 down), 160 (103 up and 57 down) and 78 (45 up and 33 down) proteins in the PQ-2 d, 7 d, and 14 d groups, respectively, and there was significant difference of protein expression . The subcellular localization analysis showed that compared with the control group, the differentially-expressed proteins in the PQ-2 d and -7 d groups were mainly distributed in the extracellular space, while in the PQ-14 d group were mainly distributed in the nuclear. GO analysis showed that compared with the control group, the differentially-expressed proteins in the PQ-2 d and PQ-7 d groups were mainly involved in humoral immunity and coagulation-related reactions, while in the PQ-14 d group were mainly involved in chemotactic and regulatory responses such as neutrophil aggregation. The KEGG signaling pathway analysis showed that the complement and coagulation cascades was the most important pathway in the PQ-2d and PQ-7 d groups, while metabolism of xenobiotics by cytochrome P450 was the most important pathway in the PQ-14 d group.Conclusions:It is the first time that TMT was used to analyze PQ-induced lung injuries in mice model at different time points. This study demonstrates the molecular mechanism of PQ-induced lung injuries at protein levels, and elucidates that humoral immunity and complement-coagulation pathways charge the main role of PQ-induced lung injuries. This study may provide an important theoretical basis for further research and clinical treatment.

Objective To investigate the incidence, influencing factors and intervention of gestrinone-related abnormal uterine bleeding at different dosage of gestrinone in the clinical treatment. Methods This was a multicenter, randomized, control study of 195 Chinese women with endometriosis or adenomyosis from June 2011 to November 2013. The subjects were randomized into three groups with oral administration of gestrinone, 2.5 mg dose at one time;twice a week group:67 cases with oral administration twice a week last three months;double dose first month group:67 cases with oral administration triple times a week at first month, then twice a week for two months; three times a week group: 61 cases with oral administration three times a week last three months. The improvement of the abnormal uterine bleeding, the changes in estrogen, liver function and blood coagulation were evaluated. At the same time, B-ultrasound examination evaluation were performed. Results (1) Three months later, the incidence of abnormal uterine bleeding in twice a week group was 30%(20/67), in double dose first month group and three times a week group were 7%(5/67) and 16%(10/61) respectively, there were significant difference between three groups (P<0.05). The incidence in double dose first month group was the most lower. (2) Univariate analysis showed that the dosage and ovarian size were the significant factors for abnormal uterine bleeding (OR=0.461, P=0.003; OR=0.303, P=0.016); logistic regression analysis demonstrated that the risk of abnormal uterine bleeding in double dose first month group was the lowest when compared with twice a week group and three times a week group, the risk in twice a week group was 5-fold higher than that in double dose first month group (OR=0.211,P=0.011). The incidence of abnormal uterine bleeding in participants with abnormal ovarian volume results from ovarian cyst or ovarian surgery was significantly lower than those with normal ovarian volume (OR=0.304, P=0.018). (3) After the treatment of three months, there were no significant difference in alanine transaminase level between the groups (P>0.05). The body mass index significantly increased in three group (P<0.05), but there were no significant differences between the groups (P>0.05). As for blood coagulation, there were also no significant differences between the groups (P>0.05). Conclusions Double dose of gestrinone in the first month could significantly decrease the incidence of gestrinone-related abnormal uterine bleeding. It is a more optimied dosage of gestrinone and without severe side effects. Clinical trial registration Chinese Clinical Trial Registry, registration number: ChiCTR- TRC-12002327.

Objective To explore the difference between interval storage and continuous storage of dynamic imagines in contrast enhanced ultrasound (CEUS) quantitative analysis. Methods Two CEUS were performed for each of fifteen participants using interval storage and continuous storage of dynamic images. A number of parameters were analyzed including rising time (RT), time to peak (TTP), mean transit time (MTT), maximum intensity (IMAX), and area under the curve (AUC). The disk usage and time consumpation were also compared for analysis. Results There were no differences in RT, TTP, MTT, IMAX, AUC between the two groups (t=1.028, 1.012, 0.558, 0.223, 0.556, P=0.322, 0.329, 0.586, 0.826, 0.587). There was significantly positive correlations between them (r=0.989, 0.992, 0.867, 0.865, 0.947, all P<0.05). The disk usage in interval storage group was about 1/3 of that in contiunous storage group. And the interval storage method could saved 25-30 min in each case. Conclusion Interval storage is worthy for further clinical application on the groud of its disk usage sparing and less time consumpation without compromising the image quality for analysis.

Objective To observe the difference between skeletal age of hand and wrist and chronological age and explore the reliability of CHN radiographic atlas method to assess the skeletal age of hand and wrist in children and adolescent.Methods Total 1397 healthy children (666 boys,731 girls;age range,1.0-18.0 years old) with hand and wrist injury from 2007 to 2011 were selected.Forty groups (n =20 for boys and girls,respectively) were classified according to CHN radiographic atlas method.The radiographs of hand and wrist were assessed by CHN radiographic atlas method,the relations between skeletal age and chronological age were investigated by using Wilcoxon signed ranks test.Results According to the CHN radiographic atlas method,the difference in 1.0 to 3.9 years old,7.0 to 7.9 years old and 9.0 to 15.9 years old boy groups between skeletal age and the chronological age had statistical significance (P ＜0.05) ; the difference in 1.0 to 2.9 years old,8.0 to 11.9 years old,12.6 to 14.9 years old,and 17.0 to 18.0 years old girl groups between skeletal age and the chronological age had statistical significance (P ＜ 0.05).Besides,these skeletal age was higher than the chronological age.Conclusions Skeletal age assessed by the CHN radiographic atlas method in a majority of age groups was higher than chronological age.It should be cautious to estimate the contemporary Chinese children skeletal age of hand and wrist when using the CHN radiographic atlas method.