[Comparison of the application of new and old specification for occupational health surveillance of radiation workers and analysis of influencing factors].

Objective: To investigate the impact of the implementation of GBZ 98-2020 "Health Requirements and Surveillance Specifications for Radiation Worker" on the results of occupational health examination for radiation workers. Methods: In April 2022, the subjects of the study were the radiation workers who underwent occupational health examination in Occupational Disease Prevention and Treatment Institute of Hefei. The radiation workers whose registration period was from May 1, 2021 to April 30, 2022 were the new standard group, and the occupational health surveillance standard was GBZ 98-2020 "Health Requirements and Surveillance Specifications for Radiation Worker". The radiationl workers registered from May 1, 2020 to April 30, 2021 were the old standard group, whose occupational health surveillance standards were GBZ 98- 2017 "Health Requirements for Radiation Workers" and GBZ 235-2011 "Specifications for Occupational Health Surveillance for Radiation Workers". To analyze whether there were differences between the two groups in the detection rate of missing items in the examination, re-examination, and the detection rate of occupational contraindications. The radiation workers whose occupational health examination results showed re-examination and/or occupational contraindications were judged to be in the unqualified group. Univariate and multivariate logistic regression analysis was used to find the factors affecting the determination of unqualified group. Results: The missing item detection rate of radiation workers in the new standard group was 3.04% (63/2074) , significantly higher than that in the old standard group (0.68%, 14/2054) (P<0.05) . The re-examination and occupational contraindications detection rates in the new standard group were 5.93% (123/2074) and 0.58% (12/2074) , respectively, which were significantly lower than those in the old standard group (13.83%, 284/2054) and 2.34% (48/2054) (P<0.05) . The missing item detection rate of males in the new standard group was 2.78% (40/1440) , which was significantly higher than that in the old standard group (0.72%, 11/1536) (P<0.05) . The re-examination and occupational contraindications detection rates of males in the new standard group were 3.61% (52/1440) and 0.21% (3/1440) , respectively, which were significantly lower than those in the old standard group (12.17%, 187/1536) and 2.08% (32/1536) (P<0.05) . The missing item detection rate of females in the new standard group was 3.63% (23/634) , which was significantly higher than that in the old standard group (0.58%, 3/518) (P<0.05) . The re-examination detection rate of females in the new standard group was 11.20% (71/634) , which was significantly lower than that of females in the old standard group (18.73%, 97/518) (P<0.05) . Univariate logistic regression analysis showed that gender, radiation classification, determination basis, occupational health examination category, and registration category were all influencing factors for the unqualified occupational health examination results of radiation workers (P<0.05) . Multivariate logistic regression analysis showed that the risk of being judged as unqualified based on the old standard was 2.466 times that of the new standard (95%CI: 1.975-3.080, P<0.05) , and the risk of being judged as unqualified for females was 1.869 times that of males (95%CI: 1.498-2.333, P<0.05) , the risk of being judged as unqualified for radiation workers during and after employment was 0.802 times that of pre-employment individuals (95%CI: 0.650-0.989, P<0.05) , and the risk of being judged as unqualified for re-examined individuals was 4.056 times that of initial examinees (95%CI: 3.161-5.203, P<0.05) . Conclusion: The results of occupational health examination of radiation workers are related to the determination basis, gender, occupational health examination category, and registration category. The implementation of GBZ 98-2020 "Health Requirements and Surveillance Specifications for Radiation Worker" may reduce the detection rate of unqualified personnel.

Octahedral Distortion and Displacement-Type Ferroelectricity with Switchable Photovoltaic Effect in a 3d

Because of the half-filled t_{2g}-electron configuration, the BO_{6} octahedral distortion in a 3d^{3} perovskite system is usually very limited. In this Letter, a perovskitelike oxide Hg_{0.75}Pb_{0.25}MnO_{3} (HPMO) with a 3d^{3} Mn^{4+} state was synthesized by using high pressure and high temperature methods. This compound exhibits an unusually large octahedral distortion enhanced by approximately 2 orders of magnitude compared with that observed in other 3d^{3} perovskite systems like RCr^{3+}O_{3} (R=rare earth). Essentially different from centrosymmetric HgMnO_{3} and PbMnO_{3}, the A-site doped HPMO presents a polar crystal structure with the space group Ama2 and a substantial spontaneous electric polarization (26.5 µC/cm^{2} in theory) arising from the off-center displacements of A- and B-site ions. More interestingly, a prominent net photocurrent and switchable photovoltaic effect with a sustainable photoresponse were observed in the current polycrystalline HPMO. This Letter provides an exceptional d^{3} material system which shows unusually large octahedral distortion and displacement-type ferroelectricity violating the "d^{0}-ness" rule.

[Based on CT radiomics model for predicting the response to first-line chemotherapy of diffuse large B-cell lymphoma].

Objective: To investigate the potential value of CT Radiomics model in predicting the response to first-line chemotherapy in diffuse large B-cell lymphoma (DLBCL). Methods: Pre-treatment CT images and clinical data of DLBCL patients treated at Shanxi Cancer Hospital from January 2013 to May 2018 were retrospectively analyzed and divided into refractory patients (73 cases) and non-refractory patients (57 cases) according to the Lugano 2014 efficacy evaluation criteria. The least absolute shrinkage and selection operator (LASSO) regression algorithm, univariate and multivariate logistic regression analyses were used to screen out clinical factors and CT radiomics features associated with efficacy response, followed by radiomics model and nomogram model. Receiver operating characteristic (ROC) curve, calibration curve and clinical decision curve were used to evaluate the models in terms of the diagnostic efficacy, calibration and clinical value in predicting chemotherapy response. Results: Based on pre-chemotherapy CT images, 850 CT texture features were extracted from each patient, and 6 features highly correlated with the first-line chemotherapy effect of DLBCL were selected, including 1 first order feature, 1 gray level co-occurence matrix, 3 grey level dependence matrix, 1 neighboring grey tone difference matrix. Then, the corresponding radiomics model was established, whose ROC curves showed AUC values of 0.82 (95% CI: 0.76-0.89) and 0.73 (95% CI: 0.60-0.86) in the training and validation groups, respectively. The nomogram model, built by combining validated clinical factors (Ann Arbor stage, serum LDH level) and CT radiomics features, showed an AUC of 0.95 (95% CI: 0.90-0.99) and 0.91 (95% CI: 0.82-1.00) in the training group and the validation group, respectively, with significantly better diagnostic efficacy than that of the radiomics model. In addition, the calibration curve and clinical decision curve showed that the nomogram model had good consistency and high clinical value in the assessment of DLBCL efficacy. Conclusion: The nomogram model based on clinical factors and radiomics features shows potential clinical value in predicting the response to first-line chemotherapy of DLBCL patients.

[Effects of biologics on psychological status and quality of life in patients with inflammatory bowel disease: a multicenter study].

Objective: To investigate the effects of biologics on psychological status and quality of life in patients with inflammatory bowel disease (IBD). Methods: A cross-sectional survey was conducted in 42 hospitals in 22 provinces (autonomous regions and municipalities directly under the central government) from September 2021 to May 2022. General clinical information and the use of biologics were obtained from adult patients diagnosed with IBD who voluntarily participated in the study. Psychological status was evaluated using the Generalized Anxiety Disorder (GAD-7), Patient Health Questionnaire-9 (PHQ-9), Pittsburgh Sleep Quality Index (PSQI), and Inflammatory Bowel Disease Questionnaire (IBDQ) assessment tools. Counts were analyzed via the Chi-square test, and datasets that were not normally distributed were analyzed via nonparametric tests. P<0.05 was considered statistically significant. Results: A total of 2 478 valid questionnaires were collected. The GAD-7 score of the biologics group was significantly lower than that of the non-use group [6 (2, 9) vs. 7 (3, 10), Z=-3.49, P<0.001]. IBDQ scores [183 (158, 204) vs. 178 (152, 198), Z=-4.11, P<0.001], intestinal symptom scores [61 (52, 67) vs. 58 (49, 65), Z=-5.41, P<0.001], systemic symptom scores [28 (24, 32) vs. 27 (23, 31), Z=-2.37, P=0.018], emotional ability scores [69 (58, 77) vs. 67 (56, 75), Z=-3.58, P<0.001] and social ability scores [26 (22, 29) vs. 25 (22, 29), Z=-2.52, P=0.012] in the biologics group were significantly higher than in the non-use group. GAD-7 scores [5 (2, 9) vs. 6 (3, 10), Z=-3.50, P<0.001] and PSQI scores [6 (4, 9) vs. 6 (4, 9), Z=-2.55, P=0.011] were significantly lower in the group using infliximab than in the group not using it. IBDQ scores were significantly higher in patients using vedolizumab than in those not using it [186 (159, 205) vs. 181 (155, 201), Z=-2.32, P=0.021] and were also significantly higher in the group treated with adalimumab than in the group not treated with adalimumab [187 (159, 209) vs. 181 (155, 201), Z=-2.16, P=0.030]. However, ustekinumab had no significant effect on any of the scores. Conclusion: The use of biologics is strongly associated with improvements in anxiety status and quality of life in IBD patients.

[Analysis of microsatellite instability in endometrial cancer: The significance of minimal microsatellite shift].

OBJECTIVE: To analyze the differences and characteristics of microsatellite instability (MSI) in endometrial cancer (EMC), by using colorectal cancer (CRC) as control. METHODS: In the study, 228 cases of EMC were collected. For comparative analysis, 770 cases of CRC were collected. Mismatch repair (MMR) expression was detected by immunohistochemistry (IHC), and microsatellite instability (MSI) was analyzed by PCR and capillary electrophoresis fragment analysis (MSI-PCR). MSI-PCR was detected using five mononucleotide repeat markers: BAT-25, BAT-26, NR-21, NR-24, and MONO-27. RESULTS: In EMC, we found 27.19% (62/228) of deficient mismatch repair (dMMR) using IHC, significantly higher than CRC (7.79%, 60/770). Meanwhile, subclonal expression of MMR protein was found in 4 cases of dMMR-EMC and 2 cases of dMMR-CRC. According to the criteria of major micro-satellite shift, we found 16.23% (37/228) of MSI-high (MSI-H), 2.63% (6/228) of MSI-low (MSI-L), and 81.14% (185/228) of microsatellite stability (MSS) in EMC using MSI-PCR. The discor-dance rate between MMR-IHC and MSI-PCR in EMC was 11.84% (27/228). In CRC, we found 8.05% (62/770) of MSI-H, 0.13% (1/770) of MSI-L, and 91.82% (707/770) of MSS. The discordance rate between MMR-IHC and MSI-PCR in CRC was only 0.52% (4/770). However, according to the criteria of minimal microsatellite shift, 12 cases of EMC showed minimal microsatellite shift including 8 cases of dMMR/MSS and 4 cases of dMMR/MSI-L and these cases were ultimately evaluated as dMMR/MSI-H. Then, 21.49% (49/228) of EMC showed MSI-H and the discordance rate MMR-IHC and MSI-PCR in EMC decreased to 6.58% (15/228). No minimal microsatellite shift was found in CRC. Compared with EMC group with major microsatellite shift, cases with minimal microsatellite shift showed younger age, better tumor differentiation, and earlier International Federation of Gynecology and Obstetrics (FIGO) stage. There were significant differences in histological variant and FIGO stage between the two groups (P < 0.001, P=0.006). CONCLUSION: EMC was more prone to minimal microsatellite shift, which should not be ignored in the interpretation of MSI-PCR results. The combined detection of MMR-IHC and MSI-PCR is the most sensitive and specific method to capture MSI tumors.

[Pathological evaluation of endoscopic submucosal dissection for early gastric cancer and precancerous lesion in 411 cases].

OBJECTIVE: To evaluate the pathological characteristics of endoscopic submucosal dissection (ESD) specimens for early gastric cancer and precancerous lesions, accumulating experience for clinical management and pathological analysis. METHODS: A total of 411 cases of early gastric cancer or precancerous lesions underwent ESD. According to the Japanese guidelines for ESD treatment of early gastric cancer and classification of gastric carcinoma, the clinicopathological data, pathologic evaluation, concordance rate of pathological diagnosis between preoperative endoscopic forceps biopsies and their ESD specimens (in 400 cases), as well as the risk factors of non-curative resection of early gastric cancer, were analyzed retrospectively. RESULTS: 23.4% (96/411) of the 411 cases were adenoma/low-grade dysplasia and 76.6% (315/411) were early gastric cancer. The latter included 28.0% (115/411) non-invasive carcinoma/high-grade dysplasia and 48.7% (200/411) invasive carcinoma. The concordance rate of pathological diagnosis between endoscopic forceps biopsies and ESD specimens was 66.0% (264/400), correlating with pathological diagnosis and lesion location (P < 0.01). The rate of upgraded diagnosis and downgraded diagnosis after ESD was 29.8% (119/400) and 4.2% (17/400), respectively. Among the 315 cases of early gastric cancer, there were 277 cases (87.9%) of differentiated type and 38 cases (12.1%) of undifferentiated type. In the study, 262 cases (83.2%) met with absolute indication, while 53 cases (16.8%) met relative indication. En bloc and curative resection rates were 98.1% and 82.9%, respectively. Risk factors for non-curative resection included a long diameter >20 mm (OR=3.631, 95%CI: 1.170-11.270, P=0.026), tumor infiltration into submucosa (OR=69.761, 95%CI: 21.033-231.376, P < 0.001)and undifferentiated tumor histology (OR=16.950, 95%CI: 4.585-62.664, P < 0.001). CONCLUSION: Several subjective and objective factors, such as the limitations of biopsy samples, the characteristics and distribution of the lesions, different pathological understanding, and the endoscopic sampling and observation, can lead to the differences between the preoperative and postoperative pathological diagnosis of ESD. In particular, the pathological upgrade of postoperative diagnosis was more significant and should receive more attention by endoscopists and pathologists. The curative resection rate of early gastric cancer in ESD was high. Non-curative resection was related to the long diameter, the depth of tumor invasion and histological classification. ESD can also be performed in undifferentiated early gastric cancer if meeting the indication criteria. The comprehensive and standardized pathological analysis of ESD specimens is clinically important to evaluate the curative effect of ESD operation and patient outcomes.

[Regional analysis of high risk factors of hypertensive disorders in pregnancy with organ or system impairment].

Objective: To explore the influencing factors of pregnancy-induced hypertensive disorders in pregnancy (HDP) with organ or system impairment in pregnant women, and to analyze and compare the differences of HDP subtypes in different regions of China. Methods: A total of 27 680 pregnant women with HDP with complete data from 161 hospitals in 24 provinces, autonomous regions and municipalities were retrospectively collected from January 1, 2018 to December 31, 2018. According to their clinical manifestations, they were divided into hypertension group [a total of 10 308 cases, including 8 250 cases of gestational hypertension (GH), 2 058 cases of chronic hypertension during pregnancy] and hypertension with organ or system impairment group [17 372 cases, including 14 590 cases of pre-eclampsia (PE), 137 cases of eclampsia, 2 645 cases of chronic hypertension with PE]. The subtype distribution of HDP in East China (6 136 cases), North China (4 821 cases), Central China (3 502 cases), South China (8 371 cases), Northeast China (1 456 cases), Southwest China (2 158 cases) and Northwest China (1 236 cases) were analyzed. By comparing the differences of HDP subtypes and related risk factors in different regions, regional analysis of the risk factors of HDP pregnant women with organ or system impairment was conducted. Results: (1) The proportions of HDP pregnant women with organ or system impairment in Northeast China (79.05%, 1 151/1 456), Central China (68.42%, 2 396/3 502) and Northwest China (69.34%, 857/1 236) were higher than the national average (62.76%, 17 372/27 680); the proportions in North China (59.18%, 2 853/4 821), East China (60.85%, 3 734/6 136) and South China (59.56%, 4 986/8 371) were lower than the national average, and the differences were statistically significant (all P<0.05). (2) Univariate analysis showed that the proportions of primiparas, non-Han, non-urban household registration, irregular prenatal examination and PE history in the hypertension with organ or system impairment group were higher than those in the hypertension group, and the differences were statistically significant (all P<0.05). Multivariate logistic regression analysis showed that primiparas, non-Han, non-urban household registration, irregular prenatal examination and PE history were independent risk factors for HDP pregnant women with organ or system impairment (all P<0.05). (3) Primipara: the rates of primipara in Northeast China, North China and Southwest China were higher than the national average level, while those in South China, Central China and Northwest China were lower than the national average level. Non-Han nationality: the rates of non-Han nationality in Northeast China, North China and Northwest China were higher than the national average, while those in East China, South China and Central China were lower than the national average. Non-urban household registration: the rates of non-urban household registration in Northeast China, North China, and Southwest China were lower than the national average, while those in East China, Central China were higher than the national average. Irregular prenatal examination: the rates of irregular prenatal examination in North China, South China and Southwest regions were lower than the national average level, while those in Northeast China, Central China and Northwest China were higher than the national average level. History of PE: the incidence rates of PE in Northeast China, North China, South China and Southwest China were lower than the national average level, while those in Central China and Northwest China were higher than the national average level. Conclusions: Primiparas, non-Han, non-urban household registration, irregular prenatal examination, and PE history are risk factors for HDP pregnant women with organ or system impairment. Patients in Northeast, Central and Northwest China have more risk factors, and are more likely to be accompanied by organ or system function damage. It is important to strengthen the management of pregnant women and reduce the occurrence of HDP.

[Advances in molecular mechanism and treatment of chronic mucus hypersecretion].

Chronic obstructive pulmonary disease (COPD) is one of the chronic diseases with high morbidity and mortality in China, which imposes heavy economic burden on society. Research has shown that chronic mucus hypersecretion (CMH) is an independent risk factor for persistent clinical symptoms, poor quality of life, rapid decline in lung function, acute exacerbation and increased hospitalization rate in COPD patients. CMH is a clinical phenotype of COPD with specific pathological and physiological changes. At present, the formation mechanism of CMH is not clear. There is a lack of specific and effective targeted treatments. This article aimed to review the latest research findings on CMH at home and abroad from the overview, impact on COPD patients, molecular mechanisms of formation, current treatment status and progress, and discuss potential targets for CMH treatment, to provide new ideas and directions for improving CMH and treating COPD.

Detection of blaKPC and blaNDM genes by duplex PCR with lateral flow dipsticks from sterile body fluid samples.

Duplex polymerase chain reaction with lateral flow dipsticks (duplex PCR-LFD) was developed for the simultaneous detection of beta-lactamase Klebsiella pneumoniae carbapenemase (blaKPC ) and beta-lactamase New Dehli metallo-beta-lactamase (blaNDM ) genes in body fluid samples. This method was validated using well-characterized isolates. The assessment of the specificity of duplex PCR-LFD showed that there was no cross-reactivity with other targets. The detection limit of the duplex PCR-LFD assay was 20 CFU per ml for blaKPC and blaNDM . Among 177 sterile body fluid samples tested by the duplex PCR-LFD assay, 40 were blaKPC -positive and five were blaNDM -positive. The results obtained from 122 corresponding Gram-negative bacteria which were isolated from these clinical samples and tested by duplex PCR-LFD assay showed that there were 37 strains carrying blaKPC genes in 40 blaKPC -positive samples and three strains carrying blaNDM genes in five blaNDM -positive samples. Statistical analysis indicated that there was no significant difference between the direct detection of blaKPC and blaNDM genes in clinical sterile body fluid samples and their corresponding clinical isolates. Therefore, duplex PCR-LFD can be effective for the simultaneous detection of blaKPC and blaNDM in clinical isolates and directly from clinical samples, which may be helpful for the administration of appropriate antimicrobial treatment.

[C-reactive protein is associated with impaired working capacity in Chinese patients with ankylosing spondylitis in paid employment: the real-world evidence from Smart-phone SpondyloArthritis Management System].

To investigate the relationship between serum C-reactive protein (CRP) levels and work impairment in patients with ankylosing spondylitis (AS) based on real-world evidence. Outpatients with confirmed AS at Chinese PLA General Hospital were recruited consecutively by Smart-phone SpondyloArthritis Management System (SpAMS) from April 2016 to April 2018. The relationship between CRP and work productivity and activity impairment questionnaire (WPAI) were evaluated. Five hundred and fifty-one outpatients with AS in paid employment were recruited. The presenteeism, overall work impairment, and activity impairment rates increased by 1.4% (1.1%, 1.8%), 1.1% (0.5%, 1.6%), and 1.7% (1.3%, 2.1%), respectively, for every 10 mg/L increase in the CRP level (all P value<0.01). However, the CRP level was not associated with absenteeism after adjusting for covariates [0.5%(-0.4%, 1.0%),P>0.05]. There is a significant association between increased serum CRP levels at baseline and the previous 7-day work impairment in patients with AS. Higher CRP levels contribute to worse presenteeism, overall work impairment, and activity impairment rates, which suggests the necessity of monitoring CRP on treatment, and also indicates that anti-inflammatory therapy may be effective for improving work productivity.

[Clinical analysis of 5 cases of dermatomyositis complicated with macrophage activation syndrome].

To investigate the clinical and immunological features of dermatomyositis (DM) complicated with macrophage activation syndrome (MAS). The demographic and clinical characteristics of five patients diagnosed with DM complicated with MAS hospitalized in the Department of Rheumatology and Immunology, Peking University People ' s Hospital from 2011 to 2021 were collected. The results of clinical manifestations, laboratory tests, immunological features, treatments and prognosis were analyzed and summarized. In this study, five female patients in Peking University People's Hospital with an average age of 63.8 (44.0-83.0) years and an average disease duration of 16.1 (1.5-48.0) months. All the patients had typical DM rash (such as heliotrope sign, V/shawl sign or Gottron's sign/papules). They all had muscle involvement (including myalgia or muscle weakness). Two patients had positive myositis-specific antibodies (MSAs), in which case 1 had anti-TIF1-γ antibody and case 5 had anti-NXP-2 antibody. Four patients had interstitial lung disease except case 3. All of the cases developed MAS in the active stage of DM. Common manifestations of MAS in these five patients included high-grade fever, cytopenia, decreased fibrinogen, elevated ferritin and increased soluble CD25. Case 1 presented with neutropenia (0.6×109 /L), thrombocytopenia (26.0×109 /L), hypofibrinogenemia (0.9 g/L), markedly elevated ferritin (26 331.0 µg/L), decreased NK cell activity. Case 2 had anaemia (hemoglobin 81.0 g/L), thrombocytopenia (55.0×109 /L), hypertriglyceridemia (4.7 mmol/L), hypofibrinogenemia (1.2 g/L), elevated ferritin (>100 000.0 µg/L), hemophagocytosis in bone marrow. Case 3 had anaemia (hemoglobin 88 g/L), decreased fibrinogen (1.9 g/L), increased ferritin (>27 759.0 µg/L), splenomegaly, hemophagocytosis in bone marrow. Case 4 suffered from neutropenia(0.3×109 /L), anaemia(hemoglobin 78 g/L), hypertriglyceridemia (4.2 mmol/L), hypofibrinogenemia (0.9 g/L), increased ferritin (>100 000.0 µg/L), and decreased NK cell activity. Case 5 presented anaemia (hemoglobin 60.0 g/L), thrombocytopenia (67.0×109 /L), hypertriglyceridemia (12.7 mmol/L), decreased fibrinogen (1.1 g/L), and elevated ferritin (>923.0 µg/L). All the patients were treated with methylprednisone pulse therapy (200-500 mg) combined with cyclosporine while case 5 received rituximab after methylprednisone pulses. In addition, case 3 also received the combination of mycophenolate mofetil. Case 1 was given etoposide while case 4 was treated with cyclophosphamide and repeated plasmapheresis at the same time. Moreover, intravenous immunoglobulin was added meantime apart from case 3. The condition of four patients improved significantly, nevertheless case 4 experienced recurred pulmonary symptoms and died of respiratory failure. As for complications about infection, case 2 had bacterial infection with high level procalcitonin (PCT) before MAS treatment and condition was improved after empiric antibacterial therapy. Case 3 had cytomegalovirus DNAemia before diagnosis of MAS and viral titer turned negative after ganciclovir therapy. After treatment of MAS, four patients developed cytomegalovirus DNAemia except case 3, in which case 5 was co-infected with bacteria. To sum, DM complicated with MAS is relatively rare, and its patients are of ten in life-threatening condition. Early detection, treatment and prevention of infection during treatment are critical to improve the prognosis.

[Timing of starting veno-venous extracorporeal membrane oxygenation].

Veno-venous extracorporeal membrane oxygenation (VV-ECMO) is mainly used for reversible acute respiratory failure that is difficult to correct with mechanical ventilation and other conventional measures or preparation of lung transplantation. Acute respiratory distress syndrome (ARDS) is a typical clinical syndrome of acute respiratory failure. The timing of starting VV-ECMO in severe ARDS still face many controversies and challenges. This paper we discuss the current feasible assessment methods of when to start VV-ECMO in ARDS, such as, optimization of mechanical ventilation parameters, monitoring of respiratory dynamics and hemodynamics, assessment of lung recruitability and electrical impedance tomography (EIT) real-time monitoring, etc.

[Diagnostic values of cyclin D1 immunocytochemistry and molecular testing in preoperative fine needle aspiration of undeterminate thyroid nodules].

Objective: To assess the value of cyclin D1 immunocytochemistry combined with a small panel molecular analysis in indeterminate cytological diagnosis of Bethesda category Ⅲ-Ⅴ. Methods: A consecutive cohort of 96 thyroid FNA specimens with indeterminate diagnosis (TBSRTC category Ⅲ-Ⅴ) and available histopathologic follow-up data were collected between December 2018 and December 2021 in Department of Pathology, Beijing Hospital. The cases were evaluated by cyclin D1 immunocytochemistry and molecular testing of BRAFV600E or a small panel of markers (BRAF, N-RAS, H-RAS, K-RAS and TERT) in the FNA specimens. The identification of the optimal cut-off point of cyclin D1 for the diagnosis of malignancy was evaluated using the receiver operating characteristic (ROC) curves and the assessment of the area under the ROC curve (AUC). The specificity, sensitivity, positive predictive value (PPV) and negative predictive value (NPV) of all these markers were evaluated with the crosstabs and significance was calculated. Results: Ninty-six patients with 96 thyroid nodules were enrolled, including 42 cases of TBSRTC-III, 10 cases of TBSRTC-IV and 44 cases of TBSRTC-V. There were 79 females and 17 males with a median age of 47 years (range, 25 to 75 years). A 7.5% cut-off value for positive cyclin D1 nuclear immunostaining in thyroid cells demonstrated 100% PPV, 57.1% NPV, 81.0% sensitivity and 100% specificity for thyroid malignancy diagnosis. The sensitivity of the BRAFV600E mutation test or combined with a small panel test alone for thyroid malignancy diagnosis were 65.5% and 69.0% respectively. The sensitivity for thyroid malignancy diagnosis increased to 94.0% and 95.2% respectively when combining the cyclin D1 immunocytochemistry with the molecular test, and the specificities remained 100% and 91.7% respectively.The accuracy of cyclin D1 immunocytochemistry combined with a small panel of molecular test in detecting thyroid malignancy increased to 94.8% compared to using these markers alone. Conclusions: The addition of cyclin D1 immunocytochemistry and a small panel of molecular testing to FNA cytology can increase the sensitivity and NPV of cytology in indeterminate categories, and this supplementary approach provides a simple, accurate and convenient diagnostic method for reducing unnecessary thyroidectomies.

[Transcriptomic analysis of tuberculosis peptide-based vaccine MP3RT in humanized mice].

Objective: To identify the differentially expressed genes (DEGs) induced by tuberculosis peptide-based vaccine MP3RT in a humanized mouse model using transcriptomics technology. Methods: This study was conducted from August 2019 to February 2022. We used edgeR software to screen DEGs with a fold change greater than or equal to 1.5 and a P value less than 0.05 as screening conditions. Gene ontology (GO), Kyoto encyclopedia of genes and genomes (KEGG), and protein interaction network analyses were performed on the screened DEGs. Then, these DEGs were verified by RT-qPCR and statistically analyzed by GraphPad Prism 8 software. Results: A total of 367 DEGs (214 up-regulated and 153 down-regulated) were identified by transcriptomics. Bioinformatics analysis showed that the GO enrichment of the DEGs mentioned above significantly focused on cell metabolism, growth, apoptosis, inflammation, and other terms. In contrast, the KEGG enrichment significantly focused on inflammatory pathways such as the MAPK signaling pathway. Protein interaction network analysis showed that protein Abl1 had the highest aggregation, the highest aggregation coefficient, and the best connectivity. RT-qPCR results showed that gene expressions of cpne4 (t=2.48, P=0.048 0), h2-q10 (t=2.95, P=0.025 6), mef2c (t=2.87, P=0.028 4), cr2 (t=3.23, P=0.178), ablim1 (t=2.91, P=0.033 5), dll1 (t=2.70, P=0.027 3) and ms4a2 (t=3.03, P=0.019 2) genes in the MP3RT group were significantly up-regulated than those in the PBS group, while gene expressions of cd163l1 (t=2.56, P=0.043 0), il1r1 (t=2.91, P=0.022 7) and cd34 (t=2.42, P=0.046 2) genes in the MP3RT group were significantly down-regulated than those in the PBS group. Conclusions: The MP3RT vaccine induced 367 DEGs in humanized mice, which were associated with metabolic and immune responses. Furthermore, we found that p38 MAPK and JNK/MAPK signaling pathways played an important role in the molecular mechanism of the MP3RT vaccine.

[Early histological changes detected by confocal microscopy in patients with advanced keratoconus receiving collagen cross-linking therapy].

Objective: To investigate the early histological changes by confocal microscopy of patients with advanced keratoconus receiving collagen cross-linking therapy. Methods: In this prospective case series study, confocal microscopy was used to observe 23 patients (32 eyes) who were diagnosed with advanced keratoconus and treated with collagen cross-linking at the Department of Ophthalmology, Chinese PLA General Hospital from September 2017 to March 2019, aged (26±10) year. All patients were examined before and at 1 week, 1 month and 3 months after the therapy. The tissue structure changes, the density of nerve fibers, stromal cells and endothelial cells, and the depth of the corneal stroma were recorded and compared. The overall differences at different times were compared by repeated measurement analysis of variance or Friedman test, and the pairwise comparison was corrected by LSD-t test or Bonferroni test. Results: One week after collagen cross-linking, the epithelial cells were in the repair stage, showing an increased nucleolar size and an enhanced reflection, and the activated cells could be detected under the epithelium. The superficial corneal stroma was swollen and spongiform, while the deep corneal stroma was patchy or cord-like, scattered and with a strong reflection. One month after the therapy, epithelial cells recovered, subepithelial nerves began to grow, the superficial corneal stroma still showed a spongy structure, and the reflection was further enhanced. The activation of the deep corneal stroma exhibited as thicker plaques or cord-like structure. Three months after the therapy, the continuous elongation of single nerve fibers could be detected occasionally. There was statistically significant difference in the density of nerve fibers before and early after the therapy (F=233.30, P<0.001). Compared with the preoperative value [(14.60±2.57) mm/mm2], the density of subepithelial nerve fibers decreased significantly in the early postoperative period, which was (0.51±0.31), (3.65±2.21) and (8.50± 4.02) mm/mm2, respectively, at 1 week, 1 month and 3 months, and there were significant differences between different time points (all P<0.05). There was also statistically significant differences in the density of anterior stromal cells before and early after the therapy (χ2=92.48, P<0.001). Compared with the preoperative value [347.00(345.00,395.75) cells/mm2] the density of anterior stromal cells decreased significantly in the early postoperative period, which was 2.00(1.00,5.75), 2.50(1.00,5.75) and 79.00(64.25,94.00) cells/mm2, respectively, at 1 week, 1 month and 3 months, and there were significant differences between different time points (all P<0.05). Within 3 months after the therapy, the depth of the corneal stroma observed by confocal microscopy ranged from 245 to 536 µm, with an average of (400.56±86.12) µm. Histologically, the depth of the corneal stroma ranged from 245 to 536 µm [average, (402.13±89.20) µm], from 251 to 527 µm [average, (399.88±85.92) µm] and from 259 to 530 µm [average, (399.69±85.94) µm] at 1 week, 1 month and 3 months, respectively, with no significant difference (F=0.797, P=0.455). There was no significant difference in the density of posterior stromal cells [(260.6±33.2) cells/mm2 preoperatively, (264.4±44.5) cells/mm2 at 1 week, (263.9±37.6) cells/mm2 at 1 month and (266.3±40.2) cells/mm2 at 3 months] and endothelial cells [(2 707±152.6) cells/mm2 preoperatively, (2 704±148.5) cells/mm2 at 1 week, (2 705±152.6) cells/mm2 at 1 month and (2 704±150.1) cells/mm2 at 3 months] between different time points (F=1.380, 1.011; P=0.259, 0.351). Conclusions: Confocal microscopy is able to clearly document the early morphological characteristics after collagen cross-linking in the treatment of keratoconus, including the epithelial and subepithelial nerve injury repair, the spongiform superficial corneal stroma, the patchy or cord-like deep corneal stroma, and the relatively stable stromal depth change.

[The role of TNF-α/TNFR1 inhibiting autophagy of M1-type Kupffer cells in liver injury in trichloroethylene-sensitized mice].

Objective: To detect the expression levels of M1-type polarization and autophagy-related indicators in the liver of trichloroethylene (TCE) -sensitized mice, and to explore the role of liver tumor necrosis factor-α (TNF-α) and tumor necrosis factor receptor 1 (TNFR1) in regulating M1-type Kupffer cells autophagy in liver injury in TCE-sensitized mice. Methods: In November 2019, according to simple random grouping, 45 SPF grade BALB/c female mice (6-8 weeks old) were divided into 4 groups: blank control group (n=5) , solvent control group (n=5) , TCE treatment group (n=18) , TCE+R7050 (inhibitor) treatment group (n=17) . Transdermally sensitized mice, 24 h after the last challenge, the mice were divided into TCE sensitized group and TCE non-sensitized group according to the skin reaction score. The livers of mice were harvested, and the pathological changes of the livers were observed under light and electron microscopes. Western blotting was used to detect the expressions of TNF-α, TNFR1 and autophagy-related indexes. The expression of inducible nitric oxide synthase (iNOS) , a marker of M1-type Kupffer cells, was detected by immunohistochemistry, and the occurrence of autophagy in M1-type Kupffer cells was detected by immunofluorescence double-labeling method. Results: The sensitization rate of TCE treatment group was 38.9% (7/18) , and TCE+R7050 treatment group was 35.3% (6/17) , with no significant difference between the two groups (P=1.000) . Compared with the blank control group, mice in the TCE sensitized group had abnormal liver ocytes, obvious liver injury, reduced mitochondria and broken endoplasmic reticulum. Western blotting results showed that the expressions of TNF-α and TNFR1 protein in the liver of the mice in the TCE sensitized group increased, the expression of iNOS protein in M1-type Kupffer cells increased, and the expressions of autophagic microtubule-associated protein 1 light-chain 3 (LC3B) and Beclin1 protein were decreased (P<0.05) . The results of immunohistochemistry showed that iNOS was not significantly expressed in the blank control group and solvent control group, and a small amount of expression was found in the TCE non-sensitized group, the positive staining area was obvious in TCE sensitized group, and the expression of iNOS was significantly increased (P<0.05) . Immunofluorescence results showed that the iNOS protein levels in the blank control group, solvent control group and TCE non-sensitized group were lower, and only partially colocalized with P62; the colocalization of iNOS with P62 in the TCE sensitized group was significantly increased. Conclusion: TNF-α/TNFR1 signaling pathway may promote liver injury in TCE-sensitized mice by inhibiting autophagy of M1-type Kupffer cells.

A radiomics-based model to differentiate glioblastoma from solitary brain metastases.

AIM: To differentiate glioblastoma (GBM) from solitary brain metastases (MET) using radiomic analysis. MATERIALS AND METHODS: Two hundred and fifty-three patients with solitary brain tumours (157 GBM and 98 solitary brain MET) were split into a training cohort (n=178) and a validation cohort (n=77) by stratified sampling using computer-generated random numbers at a ratio of 7:3. After feature extraction, minimum redundancy maximum relevance (mRMR) and the least absolute shrinkage and selection operator (LASSO) were used to build the radiomics signature on the training cohort and validation cohort. Performance was assessed by radiomics score (Rad-score), receiver operating characteristic (ROC) curve, calibration, and clinical usefulness. RESULTS: Eleven radiomic features were selected as significant features in the training cohort. The Rad-score was significantly associated with the differentiation between GBM and solitary brain MET (p<0.001) both in the training and validation cohorts. The radiomics signature yielded area under the curve (AUC) values of 0.82 and 0.81 in the training and validation cohorts to distinguish between GBM and solitary brain MET. CONCLUSIONS: The radiomics model might be a useful supporting tool for the preoperative differentiation of GBM from solitary brain MET, which could aid pretreatment decision-making.

Peri-prostatic adipose tissue measurements using MRI predict prostate cancer aggressiveness in men undergoing radical prostatectomy.

OBJECTIVES: To evaluate the effect of peri-prostatic adipose tissue (PPAT) measurements using preoperative MRI on the prediction of prostate cancer (PCa) aggressiveness in men undergoing radical prostatectomy (RP). METHODS: We performed a retrospective study on 179 consecutive patients receiving RP from June 2016 to October 2018. Clinical characteristics were collected. PPAT measurements including peri-prostatic fat area (PPFA) and peri-prostatic fat area to prostate area (PA) ratio (PPFA/PA) were calculated by MRI. Multivariable logistic regression analysis was performed to identify independent predictors of PCa lymph node metastasis (LNM). The predictive performance was estimated through ROC curves. Nomograms were created based on the predictors. RESULTS: Pathologic Gleason score positively correlated with digital rectal examination (DRE), PSA, PPFA/PA, P504S, and Ki-67 (all P < 0.05). ROC curves revealed that high PPFA and high PPFA/PA were associated with LNM (both P < 0.05). Multivariate analysis revealed that high PPFA/PA, pathologic Gleason score, pT stage, and Ki-67 were independently predictive of LNM. The nomograms were created and the C-index was 0.945. CONCLUSIONS: PPFA/PA is an independent predictor for LNM along with Gleason score, pT stage, and Ki-67. PPFA/PA may help predict LNM in men undergoing RP, thus providing adjunctive information for therapeutic strategy and prognosis.

Speciation and Potential Ecological Risk of Heavy Metals in Soils from Overlapped Areas of Farmland and Coal Resources in Northern Xuzhou, China.

Contamination caused by heavy metals (HMs) in soil of overlapped area of farmland and coal resources (OAFCR) has impact on crops. The concentrations and speciation of As, Cd, Cr, Cu, Pb and Zn were investigated in topsoil of an OAFCR in Xuzhou, China. The results showed that mean concentrations of all six metals were higher than the background values of Xuzhou city and Cd was moderate accumulated with the maximum Igeo equalled to 2.13. Cd showed moderate contamination level (IPi = 1.75) and potential ecological risk (Er = 44.06). Most of the total Cr, Cu, Ni, Pb, and Zn were presented in the residual forms (above 60%), and the percentages of reducible, oxidisable and residual forms of Pb were 23%, 21% and 43% respectively. Pb and Cd reflected a moderate degree of potential ecological risk and a considerable migration risk and ecotoxicity.

[Comparative analysis of high risk factors between early-onset pre-eclampsia and late-onset pre-eclampsia].

Objective: To explore the difference of high-risk factors between early-onset and late-onset pre-eclampsia, and to further understand high-risk factors of pre-eclampsia. Methods: Clinical data of pre-eclampsia pregnant women in 160 medical institutions in China in 2018 were retrospectively analyzed, including 8 031 cases of early-onset pre-eclampsia and 12 969 cases of late-onset pre-eclampsia. The proportion of high-risk factors, different body mass index (BMI) and age stratification between early-onset group and late-onset group were compared. Results: (1) Univariate analysis of high-risk factors: the proportions of high-risk factors in early-onset group and late-onset group were compared, and the differences were statistically significant (all P<0.05). Among them, the proportions of primipara and multiple pregnancy in early-onset group were lower than those in late-onset group, while the proportions of pregnant women with advanced age, irregular antenatal examination, obesity, family history of hypertension, pre-eclampsia, diabetes, kidney diseases, immune system diseases and assisted reproductive technology were higher than those in late-onset group. (2) Hierarchical analysis of BMI: the proportion of pregnant women with BMI≥24 kg/m2 in early-onset group [48.2% (2 828/5 872) vs 45.5% (4 177/9 181), respectively; P=0.001] and the proportion of pregnant women with BMI ≥28 kg/m2 in early-onset group [19.5% (1 143/5 872) vs 18.0% (1 656/9 181), respectively; P=0.028] were significantly higher than those in late-onset group. (3) Age stratification analysis: the proportion of pregnant women aged 35-39 years in the early-onset group [21.8% (1 748/8 023) vs 17.5% (2 110/12 068), respectively; P<0.01], the proportion of pregnant women 40-44 years old [6.8% (544/8 023) vs 5.4% (648/12 068), respectively; P<0.01], and the proportion of pregnant women ≥45 years old [0.7% (58/8 023) vs 0.5% (57/12 068), respectively; P=0.021] were significantly higher than those in the late-onset group. (4) Multivariate analysis: advanced age (≥35 years old), multiple pregnancy, irregular antenatal examination or transfer from other hospitals, family history of hypertension (including paternal, maternal and parental lines), previous history of pre-eclampsia, kidney diseases, immune system diseases (systemic lupus erythematosus, antiphospholipid antibody syndrome) and assisted reproductive technology pregnancy were the risk factors affecting the severity of pre-eclampsia (all P<0.05). Conclusion: Pregnant women with high risk factors such as age ≥35 years old, BMI ≥24 kg/m2 before pregnancy, family history of hypertension, history of pre-eclampsia, chronic kidney diseases, immune diseases (mainly including systemic lupus erythematosus and antiphospholipid syndrome) and assisted reproductive technology are more likely to have early-onset pre-eclampsia.