A comprehensive analysis of essential meiotic endonuclease 1 to prognosis and immune infiltration in kidney renal clear cell carcinoma.

OBJECTIVE: Clear cell renal cell carcinoma (ccRCC) is the most common type of cancer, and its molecular pathogenesis is unclear. In this study, we investigated the prognostic value of essential meiotic endonuclease 1 (EME1) in kidney renal clear cell carcinoma (KIRC). MATERIALS AND METHODS: We downloaded the RNA-Seq expression of 526 KIRC tissues and 72 normal tissues from the TCGA database and the corresponding clinical data. The gene expression profiles associated with four clear cell renal cell carcinomas were downloaded from the GEO database for analysis. The expression of EME1 in clear renal cell carcinoma and its correlation with the clinical baseline data were analyzed. Kaplan-Meier survival curve analysis was performed to assess the relationship between EME1 and patient survival. Enrichment analysis was performed to elucidate the possible functions of EME1. We also analyzed the relationship between the EME1 expression and immune infiltration through TIMER2.0 and TISIDB online databases as well as the relationship between EME1 and common immune checkpoints. RESULTS: EME1 was identified as a risk factor for overall survival in clear cell renal cell carcinoma with a hazard ratio of 3.201 (95% confidence interval: 2.430-4.215; p < 0.001). EME1 was highly expressed in KIRC compared to that in normal tissues (p < 0.001) and in the worse TNM stages and late stages (stage 3/4) (p < 0.001). High EME1 expression was strongly associated with the advanced T stage (p = 0.003), advanced N stage (p = 0.002), and advanced M stage (p = 0.006). Research data on KIRC were simultaneously collected and analyzed from the GEO database, including GSE40435, GSE53000, GSE68417, and GSE53757. EME1 predicted the survival status in KIRC patients (AUC = 0.62). We further established a nomogram including the correlation between the high and low EME1 expression, and EME1 was found to contribute to the prediction of the probability of patient survival with a c-index = 0.796. Kaplan-Meier analysis revealed a lower likelihood of survival with a high EME1 expression (p < 0.001). In addition, further bioinformatics analysis suggested that EME1 may be associated with the extent of immune infiltration in KIRC. CONCLUSIONS: An increased expression of EME1 in KIRC is thus associated with advanced clinicopathological features, possibly acting as a potential biomarker of poor prognosis in KIRC.

[The efficacy of radiotherapy based combined therapy for unresectable locally invasive bladder cancer and its associated factors analysis].

Objective: Retrospective analysis of the efficacy and influencing factors of bladder preservation integrated therapy for unresectable invasive bladder cancer confined to the pelvis was done, also including the bladder function preservation and adverse effects analysis. Methods: Sixty-nine patients with unresectable locally invasive bladder cancer who received radiotherapy-based combination therapy from March 1999 to December 2021 at our hospital were selected. Among them, 42 patients received concurrent chemoradiotherapy, 32 underwent neoadjuvant chemotherapyand 43 with transurethral resection of bladder tumors (TURBT) prior to radiotherapy. The late adverse effect of radiotherapy, preservation of bladder function, replase and metastasis and survival were followed-up. Cox proportional hazards models were applied for the multifactorial analysis. Results: The median age was 69 years. There were 63 cases (91.3%) of uroepithelial carcinoma, 64 of stage Ⅲ and 4 of stage Ⅳ. The median duration of follow-up was 76 months. There were 7 grade 2 late genito urinary toxicities, 2 grade 2 gastrointestinal toxicities, no grade 3 or higher adverse events occurred. All patients maintained normal bladder function, except for 8 cases who lost bladder function due to uncontrolled tumor in the bladder. Seventeen cases recurred locally. There were 11 cases in the concurrent chemoradiotherapy group with a local recurrence rate of 26.2% (11/42) and 6 cases in the non-concurrent chemoradiotherapy group with a local recurrence rate of 22.2% (6/27), and the difference in local recurrence rate between the two groups was not statistically significant (P=0.709). There were 23 cases of distant metastasis (including 2 cases of local recurrence with distant metastasis), including 10 cases in the concurrent chemoradiotherapy group with a distant metastasis rate of 23.8% (10/42) and 13 cases in the non-concurrent chemoradiotherapy group with a distant metastasis rate of 48.1% (13/27), and the distant metastasis rate in the non-concurrent chemoradiotherapy group was higher than that in the concurrent chemoradiotherapy group (P=0.036). The median 5-year overall survival (OS) time was 59 months and the OS rate was 47.8%. The 5-year progression-free survival (PFS) time was 20 months and the PFS rate was 34.4%. The 5-year OS rates of concurrent and non-concurrent chemoradiotherapy group were 62.9% and 27.6% (P<0.001), and 5-year PFS rates were 45.4% and 20.0%, respectively (P=0.022). The 5-year OS rates of with or without neoadjuvant chemotherapy were 78.4% and 30.1% (P=0.002), and the 5-year PFS rates were 49.1% and 25.1% (P=0.087), respectively. The 5-year OS rates with or without TURBT before radiotherapy were 45.5% and 51.9% (P=0.233) and the 5-year PFS rates were 30.8% and 39.9% (P=0.198), respectively. Multivariate Cox regression analysis results showed that the clinical stage (HR=0.422, 95% CI: 0.205-0.869) was independent prognostic factor for PFS of invasive bladder cancer. The multivariate analysis showed that clinical stages (HR=0.278, 95% CI: 0.114-0.678), concurrent chemoradiotherapy (HR=0.391, 95% CI: 0.165-0.930), neoadjuvant chemotherapy (HR=0.188, 95% CI: 0.058-0.611), and recurrences (HR=10.855, 95% CI: 3.655-32.638) were independent prognostic factors for OS of invasive bladder cancer. Conclusion: Unresectable localized invasive bladder cancer can achieve satisfactory long-term outcomes with bladder-preserving combination therapy based on radiotherapy, most patients can retain normal bladder function with acceptable late adverse effects and improved survival particularly evident in patients with early, concurrent chemoradiotherapy and neoadjuvant chemotherapy.

[Epidemiological investigation on allergic diseases related to animal dander of cats, dogs and horses].

Objective: A multicenter Chinese mainland survey was conducted to investigate the sensitization distribution characteristics of cat, dog and horse dander in patients with allergic diseases, so as to provide clinicians with epidemiological data of common animal allergens and useful information for the prevention and treatment of allergies in cats, dogs and horses. Methods: The epidemiological investigation and design was adopted. This study is based on the national epidemiological survey of allergic diseases led by the first affiliated Hospital of Guangzhou Medical University. From January to December in 2021, a total of 2 122 patients diagnosed with allergic diseases were included in the outpatient department of respiratory department/pediatrics/allergy department of 14 units such as the First Affiliated Hospital of Guangzhou Medical University, and 222 healthy subjects were included as controls from the physical examination center of the above units in the same period. All the subjects filled out the allergic disease questionnaire under the guidance of doctors, and the allergen-specific immunoglobulin E (sIgE) of cats, dogs and horses of all subjects were detected by magnetic particle chemiluminescence system. The epidemiological characteristics of three animal allergens in different diseases, ages and regions were analyzed. Chi square test was used to analyze the frequency difference between groups, t test or Mann Whitney U test was used to test the distribution difference between two groups, and one-way ANOVA or Kruskal Wallis H test was used to compare the distribution difference between multiple groups. Bar chart, Venn-plot and radar chart were drawn to show the sensitization distribution characteristics. A small number of missing values caused by subjects' omission have been excluded during the analysis. Results: The 2 122 patients with allergic diseases were 57.35% male (1 217/2 122) and 40.95% female (869/2 122), and 1.70% (36/2 122) patients had loss of gender information. The age of patients with allergic diseases was 9.0 (6.0, 28.0) years, while that of healthy controls was 29.0 (13.0, 39.0) years old, and there were 1.7% (36/2 122) and 0.9% (2/222) subjects with missing age information, respectively. The proportion of caesarean section in allergic patients was significantly higher than that in healthy controls (31.4% vs. 17.6%,χ2=16.582,P<0.001) [2.5% (54/2 122) of the patient group and 5.4% (12/222) of the control group had missing birth mode information], and the proportion of patients with allergic diseases who reported that both parents had allergic diseases was significantly higher than that of the control group (35.7% vs. 9.5%, χ2=65.171,P<0.001). Patients with allergic diseases are mainly school-age (6-12 years old) and adolescents (12-18 years old). 16.4% of patients with allergic diseases were sensitized to cat dander, 10% and 6% to dog and horse dander. The sensitization rate of cat dander in patients with rhinitis, asthma, conjunctivitis, food allergy and atopic dermatitis was the highest (16.4%-21.6%), followed by dog dander (10.2%-15.2%). The prevalence of allergic rhinitis was the highest among different animal sensitized populations. The proportion of cat, dog and horse allergens sensitized at the same time is between 10%-15%, and the proportion of any two or more animal dander sensitized at the same time is about 45%. Animal allergens are associated with respiratory allergic diseases, especially allergic rhinitis with allergic conjunctivitis. There were significant differences in the distribution of positive rates of three animal allergens in different regions, and the highest positive rate of cat dander was found in all provinces of the country. Conclusion: The sensitization rate of animal dander allergens increased significantly, and the highest was in children and adolescents. Cat dander is the most common animal allergen, followed by dog. Different animals show obvious cross or common sensitization due to their high homology.

[China guideline for the screening and early detection of prostate cancer (2022, Beijing)].

Prostate cancer (PC) is one of the malignant tumors of the genitourinary system that occurs more often in elderly men. Screening, early diagnosis, and treatment of the PC high risk population are essential to improve the cure rate of PC. The development of the guideline for PC screening and early detection in line with epidemic characteristics of PC in China will greatly promote the homogeneity and quality of PC screening. This guideline was commissioned by the Bureau of Disease Control and Prevention of the National Health Commission. The National Cancer Center of China initiated and convened a working group comprising multidisciplinary experts. This guideline strictly followed the World Health Organization Handbook for Guideline Development and combined the most up-to-date evidence of PC screening, China's national conditions, and practical experience in cancer screening. A total of fifteen detailed evidence-based recommendations were provided with respect to the screening population, technology, procedure management, and quality control in the process of PC screening. This guideline aimed to standardize the practice of PC screening and improve the effectiveness and efficiency of PC prevention and control in China.

[Early infantile epileptic encephalopathy caused by PACS2 gene variation: three cases report and literature review].

Objective: To explore the clinical features of three early-onset infantile epileptic encephalopathy (EIEE) patients with variations in phosphofurin acidic cluster sorting protein 2 (PACS2) gene and to review related literature. Methods: The clinical data and genetic features of three early infantile epileptic encephalopathy 66 (EIEE66) patients with a PACS2 gene variant diagnosed by the Department of Neurology, Wuhan Children's Hospital, Tongji Medical College, Huazhong University of Science and Technology, from January 2019 to January 2020 were retrospectively analyzed. A literature search with "PACS2 gene" "PACS2" "epileptic encephalopathy, early infantile, 66" and"early infantile epileptic encephalopathy 66" as key words was conducted at PubMed, China National Knowledge Infrastructure (CNKI), and Wanfang Data Knowledge Service Platform (up to July 2020). Case reports of patients with PACS2 gene variants and related clinical data were chosen and reviewed. Results: Case 1, a girl aged 2 years and 2 months was hospitalized because of repetitive seizures within more than two years and 6 convulsions within 2 days due to fever. The seizures occurred at the age of 7 days, characterized by focal seizures and generalized tonic-clonic seizures. Sometimes, the frequency of seizures increased with high fever. Regular treatment had not been implemented in the early stage, later seizures were controlled by valproic acid treatment. Case 2, a female 5 months of age, was admitted due to recurrent convulsions in nearly five months. Focal seizures occured at the age of 5 days. And the brain magnetic resonance imaging (MRI) confirmed abnormal cerebellar hemispheres and cerebellar vermis, as well as cerebellar dysplasia. Several antiepileptic drugs and ketogenic diet were ineffective in the early months, and later seizures were controlled with the treatment with levetiracetam and valproic acid. Case 3, a five-month-old girl, was admitted because of recurrent convulsions for nearly five months. At the age of 3 days, she had tonic seizures, and showed good response to levetiracetam and valproic acid. All the three cases were accompanied by development delay and dysmorphic facial appearance, and got seizure-free with the treatment with valproic acid. All copy-number variant analysis and trio whole exome sequencing revealed a recurrent heterozygous missense variant (c.625G>A) in PACS2 gene. No related reports were found in Chinese journals, while 4 reports were found in English literature, describing 17 patients in total. With these 3 patients included, 20 cases had only two missense PACS2 gene variants, in whom 19 cases carried the variant c. 625G>A (p.Glu209Lys) and 1 case carried the variant c. 631G>A (p.Glu211Lys). Epilepsy was the first reported symptom in all patients, and 17 cases had seizures during the first week of life. Out of the various seizure types observed, focal seizures were the predominant types (13 cases), whereas tonic, clonic, tonic-clonic seizures and non-motor seizures (such as facial flushing) were also reported. Almost all patients showed facial dysmorphism and developmental delay to different degrees. Total of 16 patients had abnormal brain MRI recordings, and 13 cases had cerebellar hypoplasia. More specifically, 7 cases showed inferior vermian hypoplasia, and 3 cases showed hypothalamic fusion anomaly. The treatment was mainly aimed to control the symptoms. And the recommended effective treatment for epilepsy has not been reported yet. Conclusions: PACS2-related early infantile epileptic encephalopathy is an autosomal dominant disease, characterized by seizure onset within the first week of life in most cases, dysmorphic facial appearance, and various degrees of developmental retardation. Treatment with valproic acid showed good effect.

[Performance of loop-mediated isothermal amplification (LAMP) assay for detection of Schistosoma japonicum infection in Oncomelania snails in schistosomiasis transmission-interrupted regions].

OBJECTIVE: To compare the effectiveness of loop-mediated isothermal amplification (LAMP) assay and microscopic examinations for detection of Schistosoma japonicum infections in Oncomelania hupensis in transmission-interrupted regions, so as to provide insights into the optimization of snail surveillance tools in these regions. METHODS: Four hilly schistosomiasis-endemic villages where transmission interruption was achieved were selected in Heqing County of Yunnan Province as the study villages, including Xinzhuang and Gule villages in hilly regions and Lianyi and Yitou villages in dam regions. Snail survey was performed by means of systematic sampling combined with environmental sampling in July 2018. All captured snails were identified for S. japonicum infections using microscopy. In addition, 10 to 20 snails were randomly sampled from each snail habitat following microscopy, numbered according to environments and subjected to LAMP assay. The positive rate of settings with S. japonicum-infected snails was compared among villages. RESULTS: A total of 7 949 living snails were captured from 83 snail habitats in 4 villages, and no S. japonicum infection was detected in snails. There were 226 mixed samples containing 1 786 snails subjected to LAMP assay, and positive LAMP assay was found in 3 mixed samples from 3 snail habitats in 2 dam villages. The positive rates of settings with S. japonicum-infected snails were comparable between Lianyi Village (one setting) and Yitou Village (2 set tings) (5.89% vs. 14.29%, P = 0.344). However, the overall positive rate of settings with S. japonicum-infected snails was significantly higher in dam villages (9.67%, 3/31) than in hilly villages (0) (P = 0.048). CONCLUSIONS: LAMP assay is more sensitive to detect S. japonicum infections in O. hupensis than conventional microcopy method, which may serve as a supplementary method for detection of S. japonicum infections in O. hupensis in high-risk snail habitats in hilly transmission-interrupted regions.

[Genetic expression differences of 11 beta-hydroxysteroid dehydrogenase in the bone microvascular endothelial cells derived from different regions of the human femoral head].

Objective: To investigate the expression levels and activation differences of 11beta-hydroxysteroid dehydrogenase (11beta-HSD) gene in bone microvascular endothelial cells (BMECs) in different regions of human femoral head. Methods: Tissue specimens of femoral heads were obtained from hip arthroplasty carried out in China-Japan Friendship Hospital from January 2017 to June 2018. And the BMECs we isolated, purified, identified and cultured from different regions of the human femoral head: in the subchondral and cancellous bone regions. The BMECs from the two regions were intervened by hydrocortisone with a series of low concentration gradients (0, 0.03, 0.06, 0.10 mg/ml) respectively. The cell phenotype and functional status of BMECs and cell migration were detected by scratch experiments, and the angiogenesis in different regions of the femoral head was observed. The mRNA and protein expression of 11beta-HSD1, 11beta-HSD2 in BMECs were detected by real-time fluorescence quantitative polymerase chain reaction (RT-PCR) and Western-blot method, respectively. Results: With the increase of the concentration of hydrocortisone, the 11beta-HSD1 mRNA and protein expression of BMECs in the subchondral and cancellous bone regions of the femoral head increased significantly, and the 11beta-HSD1 mRNA and protein expression of BMECs in the subchondral bone region was significantly lower than those in cancellous bone region (all P<0.05). The 11beta-HSD2 mRNA and protein expression of BMECs in the cancellous bone region showed a slow decrease first and then increased slightly at 0.10 mg/ml, while the expression in the subchondral bone region was the opposite. The 11beta-HSD2 mRNA and protein expression of BMECs in subchondral bone region was slightly higher than those in cancellous bone region (all P<0.05), but there was no significant statistical difference between the two regions at 0.10 mg/ml (0.123±0.018 vs 0.126±0.021, 0.577±0.231 vs 0.609±0.174, t=1.380, 0.409, both P>0.05). At different times of the 0.06 mg/ml hydrocortisone intervention, there was no significant differences in scratch closure rate, the number of BMECs lumen, the number of buds and the length of tubule branches in different regions of the femoral head (all P>0.05). Conclusion: The 11beta-HSD expression of BMECs in different regions of human femoral head is significantly different. The 11beta-HSD1 is high-expressed, but 11beta-HSD2 is low-expressed in BMECs of the cancellous bone region, and those are opposite in the subchondral bone region, which helps to explain the pathological characteristics and pathogenesis of hormonal osteonecrosis.

[Application of molecular analysis in differential diagnosis of ovarian adult granulosa cell tumors].

Objective: To investigate the application value of molecular detection in the differential diagnosis of ovarian adult granulosa cell tumors (AGCT) by analyzing FOXL2, AKT1 and DICER1 mutations in these tumors. Methods: A total of 48 cases of ovarian sex cord-stromal tumor (SCST) were selected from July 2012 to June 2019 in Beijing Obstetrics and Gynecology Hospital, including 21 adult granulosa cell tumors (AGCT), 15 fibromas/fibrothecomas, 8 Sertoli-Leydig cell tumors (SLCT) and 4 other types of ovarian SCST. Genomic DNA was extracted from the formalin-fixed paraffin-embedded tissue sections. Polymerase chain reaction amplification for FOXL2, AKT1 and DICER1 genes was performed, followed by sequencing using capillary electrophoresis. Fisher exact test was used to compare the prevalence difference of FOXL2, AKT1 and DICER1 mutations among the groups. P<0.05 was considered significant. Results: Eighteen of the 21 (85.7%) AGCT harbored FOXL2 mutation. Compared with other SCST (13.0%, 3 of 23; including fibromas/fibrothecomas and SLCT), FOXL2 mutation was significantly higher in AGCT (P<0.001). In addition, FOXL2 mutation was also detected in one fibrothecoma, two SLCT and two gynandroblastomas. DICER1 mutation was identified in four of eight SLCT, and these cases were moderately to poorly differentiated. FOXL2 mutation was found in one SLCT with DICER1 mutation. There was no DICER1 mutation in other ovarian SCST. No AKT1 mutation was detected in all the patients. Conclusions: FOXL2 mutation is a highly specific biomarker for adult AGCT and may be helpful to resolve problematic cases. Diagnosis should also be taken into consideration of the clinical and histological features as FOXL2 mutation is also found in other SCST. The detection of DICER1 mutation is helpful for the differential diagnosis of ovarian SLCT. Synchronous DICER1 and FOXL2 mutation in the SLCT has been observed, and its significance needs to be further studied.

Dexmedetomidine protects against lidocaine-induced neurotoxicity through SIRT1 downregulation-mediated activation of FOXO3a.

Lidocaine, a typical local anesthetic, has been shown to directly induce neurotoxicity in clinical settings. Dexmedetomidine (DEX) is an alpha-2-adrenoreceptor agonist that has been used as anxiolytic, sedative, and analgesic agent which has recently found to protect against lidocaine-induced neurotoxicity. Nicotinamide adenine dinucleotide-dependent deacetylase sirtuin-1 (SIRT1)/forkhead box O3 (FOXO3a) signaling is critical for maintaining neuronal function and regulation of the apoptotic pathway. In the present study, we designed in vitro and in vivo models to investigate the potential effects of lidocaine and DEX on SIRT1 and FOXO3a and to verify whether SIRT1/FOXO3a-mediated regulation of apoptosis is involved in DEX-induced neuroprotective effects against lidocaine. We found that in both PC12 cells and brains of mice, lidocaine decreased SIRT1 level through promoting the degradation of SIRT1 protein. Lidocaine also increased FOXO3a protein level and increased the acetylation of SIRT1 through inhibiting SIRT1. Upregulation of SIRT1 or downregulation of FOXO3a significantly inhibited lidocaine-induced changes in both cell viability and apoptosis. DEX significantly inhibited the lidocaine-induced decrease of SIRT1 protein level and increase of FOXO3a protein level and acetylation of FOXO3a. Downregulation of SIRT1 or upregulation of FOXO3a suppressed DEX-induced neuroprotective effects against lidocaine. The data suggest that SIRT1/FOXO3a is a potential novel target for alleviating lidocaine-induced neurotoxicity and provide more theoretical support for the use of DEX as an effective adjunct to alleviate chronic neurotoxicity induced by lidocaine.

[Clinical phenotypes of epilepsy associated with GABRA1 gene variants].

Objective: To summarize the clinical phenotypes of epilepsy in patients with GABRA1 gene variants. Methods: A total of 11 epileptic patients (4 boys and 7 girls) who were treated in the Department of Pediatrics, Peking University First Hospital from March 2016 to July 2019 and detected with GABRA1 gene heterozygous pathogenic variants by targeted next-generation sequencing were enrolled. The features of clinical manifestations, electroencephalogram (EEG), and neuroimaging were analyzed retrospectively. Results: A total of 11 epileptic patients carried GABRA1 gene pathogenic variants, of whom 10 were de novo variants and the other one was inherited from the patient's mother. Two patients had the same variants. Six variants were novel. Ages at seizure onset ranged from 3 to 14 months, and the median age was 8 months. The seizure was first observed within 1 year in 10 patients and beyond 1 year of age in 1 patient. Multiple seizure types were observed, including focal seizures in 10 patients, generalized tonic clonic seizures (GTCS) in 3 patients, myoclonic seizures in 3 patients, and epileptic spasm in 2 patients. There were 5 patients with multiple seizure types. Sensitivity to fever was observed in 9 patients, among whom 6 patients had a history of status epilepticus. Two patients had photoparoxysmal response. Five patients had abnormal EEG background, and 6 patients had abnormal discharges in EEG during interictal phase. Brain magnetic resonance imaging (MRI) was normal in all patients. Developmental delay in various degrees was present in 9 patients. Among the 11 patients, Dravet syndrome was diagnosed in 5 patients, West syndrome in 2 patients, undiagnosed early-onset epileptic encephalopathy in 1 patient, and focal epilepsy in the other 3 patients. The ages at the last follow-up ranged from 8 months to 12 years. During follow-up, 8 patients were seizure-free for 6 months to 8 years, and 1 patient had discontinuation of medication. Conclusions: In epilepsy associated with GABRA1 gene variants, de novo pathogenic variants are more common than inherited. Most epilepsy caused by GABRA1 gene variants occurs in infancy. Most patients have multiple seizures and focal seizures are common. Most patients have a comparatively favorable prognosis, but they may still have varied degrees of developmental delay.

The roles of NF-kB in the development of lung injury after one-lung ventilation.

OBJECTIVE: To explore the roles of NF-kB in the development of lung injury after one-lung ventilation. MATERIALS AND METHODS: Eighteen Sprague-Dawley (SD) rats were randomly divided into 3 groups including control group, one-lung ventilation (OL) group and NF-kB inhibitor pyrrolidine dithiocarbamate (PDTC) group, with 6 rats in each group. Rats in OL and PDTC groups were used to establish one-lung ventilation model, and rats in PDTC group were subjected to intravenous injection of NF-kB specific inhibitor PDTC at 30 min before model construction. One-lung ventilation was performed for 3 h, and arterial blood gas analyzer was used for blood gas analysis. The hemodynamics and respiratory mechanics parameters were detected. The respiratory index (RI) and oxygenation index (OI) were calculated. The pathological changes of lung tissue were observed by HE staining. The levels of TNF-α, IL-1ß, IL-6, and IL-8 in lung tissue were detected by ELISA. The expression levels of p65, p-p65, p-IκBα and IκBα and the activity of NF-Kß in lung tissue were detected by Western Blot. RESULTS: Compared with OL group, HR, RI and W/D were significantly reduced and MAP and OI were significantly increased in PDTC group (p<0.05). Compared with OL group, alveolar fluid exudation, pulmonary interstitial thickening and inflammatory cell infiltration were significantly improved in PDTC group. The levels of TNF-α, IL-1ß, IL-6 and IL-8 in PDTC group were significantly lower than in OL group (p<0.05). The ratios of p-p65/p65 and p-IκBα/IκBα and the activity of NF-kB in OL group were significantly reduced than in PDTC group (p<0.05). CONCLUSIONS: NF-kB can promote lung injury after one-lung ventilation, and the inhibition of NF-kB may be a new way for the treatment of this disease.

[KRAS mutations analysis in mucinous epithelial lesions of the endometrium].

Objective: To investigate the frequency of KRAS mutation in mucinous epithelial lesions of the endometrium, and analyze the correlation between KRAS mutation and the clinicopathologic features. Methods: The cohort included forty-three cases of mucinous epithelial lesions of the endometrium selected from July 2015 to October 2017 from Beijing Obstetrics and Gynecology Hospital, and 22 control cases. Genomic DNA was extracted from formalin-fixed paraffin-embedded tissue sections. Polymerase chain reaction amplification for KRAS exons 2 and 3 was performed, followed by sequencing using capillary electrophoresis. The Fisher exact test was used to compare the prevalence of KRAS mutation among the different groups. Results: The patients'age ranged from 33 to 77 years [mean (55.12±9.34) years, median 55 years]. None of the eight cases of endometrial hyperplasia with mucinous differentiation without atypia showed KRAS mutation. The frequency of KRAS mutations was 1/10 in endometrial atypical hyperplasia, 1/12 in endometrioid carcinoma, 4/11 in endometrial atypical hyperplasia with mucinous differentiation (EAHMD), 6/15 in endometrioid carcinoma with mucinous differentiation (ECMD) and 8/9 in mucinous carcinoma (MC), respectively. The differences were statistically significant between MC versus EC (P<0.01) and MC versus ECMD (P<0.05). Conclusion: The high frequency of KRAS mutation in EAHMD, ECMD and MC indicates that KRAS mutational activation is implicated in the pathogenesis of endometrial mucinous carcinoma.

[Clinical application of STR genotyping diagnosis for hydatidiform mole and nonmolar gestation].

Objective: To investigate the value of short tandem repeat (STR) genotyping in the diagnostic workup of molar and non-molar gestations with correlation of histological characteristics. Methods: Six hundred and fifty-six cases were selected based on clinically suspected hydropic abortion and/or molar pregnancy from July 2015 to September 2017 at Beijing Obstetrics and Gynecology Hospital. DNA was extracted from dissected chorionic villi and paired maternal endometrial FFPE tissue samples by Simplex OUP™ FFPE DNA Tissue Kit. STR genotyping was performed by PowerPlex 16 HS system. Results: DNA genotyping was informative in 649 of 656 cases, leading to identification of 215 hydatidiform mole gestations and 434 non-molar gestations. Most of non-molar gestations (375 cases, 86.4%) were diploid hydropic abortion. Various trisomy syndromes were found (53 cases, 12.2%), including trisomy 2, 3, 4, 7, 8, 13, 16 and 21. Only 2(0.5%) digynic triploid gestations were detected. Moreover, 4 cases (0.9%) of uniparental disomies (homologous or heterologous) were found. There were 196 cases with histologic diagnostic suspicious of hydatidiform moles were accurate sub-classified. Among them, 59 cases hydatidiform moles were under-diagnosed as diploid hydropic abortions, and 28 cases diploid hydropic abortions were over-diagnosed as hydatidiform moles.Compared with partial moles(PHM), there were no specific histomorphological features between the various types of non-molar gestations and partial moles for definitive diagnostic separation. There was no significant difference in the expression of p57(kip2) among PHM, trisomy and diploid hydropic abortions group (P=0.247). Conclusions: STR genotyping can distinguish non-molar gestations from early hydatidiform moles, and efficiently avoid misdiagnosis based only on histological evaluation. Therefore, using STR genotyping, not only can the overdiagnosis of non-molar pregnancy be avoided, but also individualized management can be offered to patients including monitoring of serum hCG.

[The status quo and analysis of quality control of cancer chemotherapy in 76 hospitals in Beijing].

Objective: Investigated the status quo of quality control of cancer chemotherapy in hospitals in Beijing to discover the main problems and provide the improvement measures. Methods: One medical record of cancer chemotherapy was taken every month for examination of quality control, and a total of 10 medical records in each hospital were examined. A total of 756 medical records from 76 hospitals were examined. Results: The results of analysis showed that the overall standardization and quality control of cancer chemotherapy was positively correlated with the grade of hospital. Only 36.8% of the hospitals were equipped with Pharmacy Intravenous Admixture Services (PIVAS). In terms of quality control of chemotherapy and medicine, the department of oncology had better performance than other departments (P<0.01). The scores of quality control of chemotherapy and medicine in the hospitals with clinical specialist pharmacists were 50.6 and 14.5, significantly higher than 47.2 and 12.7 of those without clinical specialist pharmacists (P<0.05). Conclusion: We should focus on the quality control of cancer chemotherapy in secondary hospitals, reinforce the training of oncology specialists, establish the admission system of oncologists, enhance the training of oncology clinical pharmacists and promote the standardization of cancer chemotherapy.

Effects of sevoflurane post-conditioning in cerebral ischemia-reperfusion injury via TLR4/NF-κB pathway in rats.

OBJECTIVE: The aim of the study was to investigate the anti-inflammatory effect of sevoflurane post-conditioning on cerebral ischemia-reperfusion injury in rats. MATERIALS AND METHODS: Thirty Sprague Dawley (SD) rats were randomly divided into 3 groups: sham operation group (Sham), ischemia/reperfusion injury (I/R) group and sevoflurane post-conditioning group (Se). Hematoxylin-eosin (HE) staining was used to observe the inflammatory response in the brain tissue. The levels of TNF-α, IL-1ß, IL-6 in serum were measured by ELISA. The mRNA and protein expression of TLR4 and NF-κB p65 were detected by RT-PCR and Western blot in the brain tissue. RESULTS: The post-conditioning of sevoflurane decreased the level of inflammatory reaction in ischemic-reperfusion rat cerebral infarction area and reduced the levels of pro-inflammatory cytokines such as TNF-α, IL-1ß, IL-6 in rats with ischemia-reperfusion injury. In addition, after treatment with sevoflurane, the mRNA and protein expression of TLR4 and NF-κBp65 in TLR4/NF-κB pathway was inhibited. CONCLUSIONS: Sevoflurane post-conditioning can decrease the inflammatory reaction in cerebral infarct area induced by cerebral ischemia-reperfusion injury in rats. The neuroprotective effect mechanism of sevoflurane may be related to TLR4/NF-κB signaling pathway.

[Current applications of artificial intelligence in tumor histopathology].

The tasks of artificial intelligence (AI) in tumor histopathology include image segmentation and classification. Currently, the specific contents including lymph node metastasis, pathological classification, grade and prognostic evaluation of malignant diseases, such as breast cancer, lung cancer and prostate cancer, have been studied by AI. Evaluation of sentinel lymph node metastasis of breast cancer has been the most mature application of AI technology, whose level can be analogous to the excellent pathologists. In the future, with the close cooperation of pathologists and engineers, the research of AI will be focus on improving the technology of simple and repetitive clinical diagnosis and differential diagnosis, such as the diagnosis of sentinel lymph node metastasis of breast cancer from biopsy frozen section and the judgment of incisal margin. Ultimately, AI will help us to precisely diagnose the tumor.

The effects of add-on exenatide to insulin on glycemic variability and hypoglycemia in patients with type 1 diabetes mellitus.

OBJECTIVE: To investigate the effect of add-on exenatide to insulin on glycemic excursion and the counter-regulatory hormone in response to hypoglycemia in patients with type 1 diabetes mellitus (T1DM). METHODS: 30 patients with T1DM were recruited and randomly assigned to exenatide + insulin-treated group (group 1, n = 15) or insulin-only-treated group (group 2, n = 15) for 4 weeks. All patients had continuous glucose monitor system (CGMS) applied at before (week-0) and after (week-4) treatment to evaluate the glycemic variability. All patients had an arginine-stimulated test at before and after treatment. Six patients from each group also had hypoglycemic clamp test to assess counter-regulatory hormone level. RESULTS: Patients in the exenatide group had significant reductions in body weight, body mass index (BMI), total insulin dose, bolus insulin dose, fructosamine, and glycemic excursion after 4 weeks' treatment. Compared with patients in group 2, the mean amplitude of glycemic excursion (MAGE) and coefficient of variation (CV) of exenatide group decreased significantly. Similarly, a significant decrease of glucagon (GLC) in the arginine-stimulated test was found in group 1. No significant changes of GLC, growth hormone (GH), cortisol (COR), epinephrine (E), and norepinephrine (NE) were found in both groups during hypoglycemia clamp test. However, patients who had residual islet function in group 1 showed an upward trend of basic C-peptide (C-P) and GLC during the hypoglycemia period. CONCLUSION: Although exenatide could inhibit glucagon secretion during euglycemia or hyperglycemia in patients with T1DM, it has no effect on GLC and counter-regulatory hormones during hypoglycemia clamp in patients with no functional residual islet test.

A comparison of clinical efficacy and economic value in Basalin- and Lantus-treated patients with type 2 diabetes using continuous glucose monitoring system.

AIM: To determine the clinical non-inferiority of recombinant glargine-Basalin vs glargine-Lantus, in treatment of type 2 diabetes mellitus (T2DM) using continuous glucose monitoring system (CGMS). METHODS: One hundred patients with T2DM were recruited. They were either regularly taking Basalin (Basalin group) or Lantus (Lantus group) (n = 50 each). CGMS was employed to real-time monitor blood glucose profile for 4 days (from day 1 to day 5). To exclude the effect of patient background, the study design was to have a blinded crossover from glargine-Basalin to glargine-Lantus on day 3, and vice versa. 24-hour mean blood glucose (24hMBG), 24-hour standard deviation of blood glucose (24hSDBG), 24-hour mean amplitude of glycemic excursion (24hMAGE), and number of glycemic excursion (NGE) every 24 h (24hNGE) were calculated for each glargine from 100 patients. RESULTS: No significant difference of 24hMBG, 24hSDBG, 24hMAGE, and 24hNGE (p > 0.05 for all) was found between Basalin and Lantus treatments. The glucose area under the curve and time when blood glucose was below 3.9 mmol/L, between 3.9 and 10.0 mmol/L, or above 10.0 mmol/L were similar between Basalin and Lantus treatment. The frequency of hypoglycemic episodes was also similar. However, the mean cost of Basalin was only 72% of Lantus's in one treatment course. CONCLUSION: Glargine-Basalin is non-inferior in clinical efficacy compared to glargine-Lantus. In view of the large difference in the cost of glargine-Basalin, it would be much more cost-effective for our patients.