BACKGROUND: Lung cancer is one of the leading causes of cancer-related mortality worldwide, with above 80% of cases be non-small cell lung cancer (NSCLC), among which lung squamous cell carcinoma (LUSC) occupies a significant proportion. Although comprehensive cancer therapies have considerably improved the overall survival of patients, patients with advanced LUSC have a poorer prognosis. Therefore, there is a need for a biomarker to predict the progress of advanced LUSC in order to improve prognosis through early diagnosis. Previous studies have shown that miRNAs are differentially expressed in lung cancer tissues and play roles as potential oncogenes or tumor suppressors. The aim of this study is to identify differentially expressed miRNAs between early-stage and advanced-stage LUSC, and to establish a set of miRNAs that can predict the progress of advanced LUSC. METHODS: Clinical data and miRNA-related data of LUSC patients were downloaded from The Cancer Genome Atlas (TCGA) database. Bioinformatic methods were applied to analyze the data. Receiver operating characteristic (ROC) curves were plotted, and various online tools were used to predict target genes, with subsequent analysis of the potential biological mechanisms of these genes. RESULTS: A total of 58 differentially expressed miRNAs were identified between the experiment group and the control group. Seven miRNAs were selected for potential construction of a miRNA biomarker through LASSO regression, and based on the area under the curve (AUC) values of each miRNA, four of these miRNAs (miR-377-3p, miR-4779, miR-6803-5p, miR-3960) were ultimately chosen as biomarkers for predicting advanced LUSC. The AUC under the ROC curve for the combined four miRNAs was 0.865. Enrichment analysis showed that these target genes were involved in several pathways, including cancer-related pathways, mitogen-activated protein kinase (MAPK) signaling pathway, serine/threonine kinase, and tyrosine kinase signaling pathways. CONCLUSIONS The combined use of miR-377-3p, miR-4779, miR-6803-5p and miR-3960 provides a good predictive ability for the progress of advanced LUSC patients, with an AUC of 0.865.
Humans ; MicroRNAs/metabolism* ; Lung Neoplasms/metabolism* ; Biomarkers, Tumor/metabolism* ; Carcinoma, Squamous Cell/pathology* ; Gene Expression Regulation, Neoplastic ; Male ; Female ; Prognosis ; ROC Curve ; Middle Aged

Objective:To preliminarily investigate the clinical outcomes of secondary loop electrosurgical excision procedure (LEEP) combined with transcervical resection of endocervical tissue (i.e., second combined surgeries) in patients with positive endocervical margins following the initial LEEP for high-grade squamous intraepithelial lesion (HSIL) or adenocarcinoma in situ (AIS) of the cervix.Methods:Patients who underwent second combined surgeries due to positive endocervical margins after the initial LEEP for cervical HSIL or AIS at Obstetrics and Gynecology Hospital, Fudan University between August 2015 and September 2023 were included. Postoperative cytological examinations, high-risk human papillomavirus (HR-HPV) testing, colposcopic biopsy results, and cervical canal length were followed up to evaluate the clinical efficacy of second combined surgeries.Results:(1) General clinical data: a total of 67 patients were enrolled, including 34 with cervical HSIL (HSIL group) and 33 with AIS (AIS group). In the HSIL group before the time of initial LEEP, the mean age was (41.3±5.3) years, with all patients positive for HR-HPV preoperatively. Preoperative cytology results revealed ≤low-grade squamous intraepithelial lesion (LSIL) in 13 cases and ≥HSIL in 21 cases. The preoperative cervical canal length was (3.71±0.17) cm. Patients in the AIS group before their the first LEEP were at an average age of (39.1±8.7) years old, with preoperative HR-HPV positive. Among them, 16 cases showed preoperative cytological results of ≤LSIL, while 17 cases showed ≥HSIL. The preoperative cervical canal length was (3.64±0.21) cm. (2) Pathological findings and postoperative follow-up of the HSIL group following second combined surgeries:in the HSIL group, the residual rate of HSIL in the endocervical canal tissue (ECT) was 24% (8/34). Out of the 34 HSIL patients, 10 cases (29%, 10/34) remained with positive endocervical margins post-second combined surgeries. Among these 10 patients, 5 cases (5/10) had no lesion detected in ECT, while the remaining 5 cases (5/10) exhibited HSIL in their ECT. Conversely, 24 patients (71%, 24/34) had negative endocervical margins after second combined surgeries. Of these 24 patients, 3 cases (12%, 3/24) were found to have HSIL in ECT, and 21 cases (88%, 21/24) had no lesion in ECT. During follow-ups conducted at 6 and 12 months post-second combined surgeries, the clearance rates of HR-HPV were 91% (31/34) and 100% (34/34), respectively. Notably, among the 29 patients (85%, 29/34) who were followed up for a period of 2 years or longer, all cases maintained a consistently negative HR-HPV status, highlighting the effectiveness of second combined surgeries in achieving long-term HR-HPV clearance (100%, 29/29). (3) Pathological findings and postoperative follow-up of the AIS group following second combined surgeries: the residual rate of AIS in the ECT following second combined surgeries among AIS patients was 15% (5/33). Out of the 33 AIS patients, 11 cases (33%, 11/33) had positive endocervical margins post-operation, among whom AIS was detected in the ECT of 2 cases (2/11), while 1 case (1/11) was diagnosed with adenocarcinoma in the cervical canal tissue (subsequently underwent radical surgery and was excluded from this study). In contrast, 22 patients (67%, 22/33) had negative endocervical margins post-operation, with AIS found in the ECT of 2 cases (9%, 2/22) and no lesions detected in the remaining 20 cases (91%, 20/22). Follow-up evaluations conducted at 6 and 12 months postoperatively revealed HR-HPV clearance rates of 91% (29/32) and 97% (31/32), respectively. All 32 (100%, 32/32) AIS patients were followed up for a duration of ≥2 years post-second combined surgeries, during which HR-HPV remained consistently negative. (4) Complications and cervical length following second combined surgeries: neither the HSIL group nor the AIS group experienced significant complications such as hemorrhage, infection or cervical canal adhesion. At the 6-month follow-up, the cervical length of both HSIL and AIS patients exceeded 3 cm. By the 12-month follow-up, the cervical length had recovered to 96.5% and 97.5% when compared to the original length, respectively, for the HSIL and AIS groups.Conclusions:For patients with HSIL or AIS who exhibit positive endocervical margins following the initial LEEP procedure, undergoing second combined surgeries presents as an optimal choice. This surgical intervention guarantees thorough excision of the lesion, and subsequent colposcopic follow-up evaluations consistently demonstrate an absence of residual disease or recurrence. Moreover, it augments the rate of sustained HR-HPV negativity, thereby contributing to more favorable clinical outcomes.

Objective To explore the possible causes of CAST/EiJ mouse susceptibility to multiple pathogens,the immune cell phenotypes in the peripheral blood and spleen of CAST/EiJ mice were analyzed to clarify their composition.Methods Classical dendritic cells(cDCs),natural killer(NK)cells,B lymphocytes,T lymphocytes,and their subsets in the peripheral blood and spleen of CAST/EiJ mice and C57BL/6J mice were detected by flow cytometry using the cell surface markers CD3,CD4,CD8,CD11b,CD11c,CD19,CD27,CD49b,and TCRβ.Results There was no significant difference in the proportion of cDCs between CAST/EiJ and C57BL/6J mice,but the cDC1 cell subset population was smaller in CAST/EiJ.The proportions of NK cells(mainly mature NK cell subsets)and T lymphocytes(mainly CD8+T cells)were both lower in CAST/EiJ mice than C57BL/6J mice,while the proportion of B cells was higher in CAST/EiJ mice than C57BL/6J mice.Conclusions The proportions of NK and T lymphocytes in CAST/EiJ mice were lower than those in C57BL/6J mice.

BACKGROUND: Lung cancer represents the main cause of cancer-related deaths worldwide, and non-small cell lung cancer (NSCLC) is the most main subtype. More than half of NSCLC patients have already developed distant metastasis (DM) at the time of diagnosis and have a poor prognosis. Therefore, it is necessary to find new biomarkers for predicting NSCLC DM in order to guide subsequent treatment and thus improve the prognosis of NSCLC patients. Numerous studies have shown that microRNAs (miRNAs) are abnormally expressed in lung cancer tissues and play an important role in tumorigenesis and progression. The aim of this study is to identify differentially expressed miRNAs in lung adenocarcinoma tissues with DM group compared to those with non-distant metastasis (NDM) group, and to construct a miRNA signature for predicting DM of lung adenocarcinoma. METHODS: We first obtained miRNA and clinical data for patients with lung adenocarcinoma from The Cancer Genome Atlas (TCGA) database. Subsequently, bioinformatics analysis, which included different R packages, Kaplan-Meier analysis, receiver operating characteristic (ROC) curve, and a range of online analysis tools, was performed to analyze the data. RESULTS A total of 12 differentially expressed miRNAs were identified between the DM and NDM groups, and 8 miRNAs (miR-377-5p, miR-381-5p, miR-490-5p, miR-519d-5p, miR-3136-5p, miR-320e, miR-2355-5p, miR-6784-5p) were screened for constructing a miRNA signature. The efficacy of this miRNA signature in predicting DM was good with an area under the curve (AUC) of 0.831. Logistic regression analysis showed that this miRNA signature was an independent risk factor for DM of lung adenocarcinoma. Next, target genes of the eight miRNAs were predicted, and enrichment analysis showed that these target genes were enriched in a variety of pathways, including pathways in cancer, herpes simplex virus I infection, PI3K-Akt pathway, MAPK pathway, Ras pathway, etc. CONCLUSIONS: This miRNA signature has good efficacy in predicting DM of lung adenocarcinoma and has the potential to be a predictor of DM of lung adenocarcinoma.
Humans ; MicroRNAs/metabolism* ; Lung Neoplasms/diagnosis* ; Male ; Neoplasm Metastasis ; Female ; Gene Expression Regulation, Neoplastic ; Middle Aged ; Prognosis ; Gene Expression Profiling ; Aged ; Biomarkers, Tumor/genetics*

Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease worldwide. Fat accumulation "sensitizes" the liver to insult and leads to nonalcoholic steatohepatitis (NASH). G protein-coupled receptor 35 (GPR35) is involved in metabolic stresses, but its role in NAFLD is unknown. We report that hepatocyte GPR35 mitigates NASH by regulating hepatic cholesterol homeostasis. Specifically, we found that GPR35 overexpression in hepatocytes protected against high-fat/cholesterol/fructose (HFCF) diet-induced steatohepatitis, whereas loss of GPR35 had the opposite effect. Administration of the GPR35 agonist kynurenic acid (Kyna) suppressed HFCF diet-induced steatohepatitis in mice. Kyna/GPR35 induced expression of StAR-related lipid transfer protein 4 (STARD4) through the ERK1/2 signaling pathway, ultimately resulting in hepatic cholesterol esterification and bile acid synthesis (BAS). The overexpression of STARD4 increased the expression of the BAS rate-limiting enzymes cytochrome P450 family 7 subfamily A member 1 (CYP7A1) and CYP8B1, promoting the conversion of cholesterol to bile acid. The protective effect induced by GPR35 overexpression in hepatocytes disappeared in hepatocyte STARD4-knockdown mice. STARD4 overexpression in hepatocytes reversed the aggravation of HFCF diet-induced steatohepatitis caused by the loss of GPR35 expression in hepatocytes in mice. Our findings indicate that the GPR35-STARD4 axis is a promising therapeutic target for NAFLD.

Objective:To isolate and culture WU polyomavirus (WUPyV), and to analyze the genome-wide evolutionary patterns, homology and population dynamics.Methods:Real-time quantitative PCR was used to detect the nasopharyngeal aspirate samples of hospitalized children with respiratory tract infection in Beijing Friendship Hospital during 2020 to 2022. Primary human airway epithelial cells cultured at the air-liquid interface were used to isolate and culture WUPyV. Whole genome sequence of the isolated strain was obtained by Sanger sequencing. For phylogenetic and evolutionary dynamics analysis, the whole genome was compared with the published whole genome sequences in GenBank database.Results:The detection rate of WUPyV was 4.7% (31/659) during 2020 to 2022, and a clinical strain BJ0593 of WUPyV type Ⅲc was successfully isolated. The homology of the whole genome and gene fragments of WUPyV was high. The average evolutionary rate of VP2 gene was about 1.256×10 -4 substitution/site every year, and the population dynamics of WUPyV tended to be flat in the last decade. Conclusions:This study successfully isolated a clinical WUPyV type Ⅲ strain for the first time, which provided the basis for further investigation on the molecular evolution and pathogenicity of WUPyV.

Objective:To analyze the risk factors of bronchopulmonary dysplasia(BPD)in very preterm infants(VPI), and to provide scientific basis for the prevention and treatment of BPD in VPI.Methods:A prospective multicenter study was designed to collect the clinical data of VPI in department of neonatology of 28 hospitals in 7 regions from September 2019 to December 2020.According to the continuous oxygen dependence at 28 days after birth, VPI were divided into non BPD group and BPD group, and the risk factors of BPD in VPI were analyzed.Results:A total of 2 514 cases of VPI including 1 364 cases without BPD and 1 150 cases with BPD were enrolled.The incidence of BPD was 45.7%.The smaller the gestational age and weight, the higher the incidence of BPD( P<0.001). Compared with non BPD group, the average birth age, weight and cesarean section rate in BPD group were lower, and the incidence of male infants, small for gestational age and 5-minute apgar score≤7 were higher( P<0.01). In BPD group, the incidences of neonatal respiratory distress syndrome(NRDS), hemodynamically significant patent ductus arteriosus, retinopathy of prematurity, feeding intolerance, extrauterine growth restriction, grade Ⅲ~Ⅳ intracranial hemorrhage, anemia, early-onset and late-onset sepsis, nosocomial infection, parenteral nutrition-associated cholestasis were higher( P<0.05), the use of pulmonary surfactant(PS), postnatal hormone exposure, anemia and blood transfusion were also higher, and the time of invasive and non-invasive mechanical ventilation, oxygen use and total hospital stay were longer( P<0.001). The time of starting enteral nutrition, cumulative fasting days, days of reaching total enteral nutrition, days of continuous parenteral nutrition, days of reaching 110 kcal/(kg·d) total calorie, days of reaching 110 kcal/(kg·d) oral calorie were longer and the breastfeeding rate was lower in BPD group than those in non BPD group( P<0.001). The cumulative doses of amino acid and fat emulsion during the first week of hospitalization were higher in BPD group( P<0.001). Multivariate Logistic regression analysis showed that NRDS, invasive mechanical ventilation, age of reaching total enteral nutrition, anemia and blood transfusion were the independent risk factors for BPD in VPI, and older gestational age was the protective factor for BPD. Conclusion:Strengthening perinatal management, avoiding premature delivery and severe NRDS, shortening the time of invasive mechanical ventilation, paying attention to enteral nutrition management, reaching whole intestinal feeding as soon as possible, and strictly mastering the indications of blood transfusion are very important to reduce the incidence of BPD in VPI.

Objective:To estimate risks of cervical intraepithelial neoplasia (CIN) Ⅱ or worse (CINⅡ +) on loop electrosurgical excisional procedure (LEEP) specimens with the diagnosis of endocervical curettage (ECC) CINⅠ compared with biopsy CINⅠ, and also to investigate the hierarchical management scheme of ECC CINⅠ based on the relevant factors of CINⅡ + risk. Methods:(1) A retrospective computer-based research for subjects enrolled in the Obstetrics and Gynecology Hospital, Fudan University from Jan. 2013 to Jun. 2021 was performed. The case group comprised women with an ECC CINⅠ (ECC results of CINⅠ with colposcopy-directed biopsy results ≤CINⅠ), and the control group comprised women with a biopsy CINⅠ (colposcopy-directed biopsy results of CINⅠ with negative ECC findings) were divided after LEEP surgery and diagnosis in the next three months. The clinical data of all patients before LEEP were analyzed, and the pathological diagnosis between two groups after LEEP was compared. (2) Variables, including age, cytology, high-risk human papillomavirus (HR-HPV), ECC results, cervical transformation zone (TZ) and colposcopy impression, were included to describe the characteristics and compare the incidence of LEEP CINⅡ +. (3) Univariate analysis and Multivariate logistic regression method were used to analyze the related factors that affect the LEEP CINⅡ + in CINⅠ patients. Further, the specific risks caused by related factors and conduct a stratified study in LEEP CINⅡ + were analyzed. Results:(1) Overall, 2 581 women with ECC CINⅠ or biopsy CINⅠ diagnosis who underwent LEEP participated in the study with the mean age (43.6±9.5) years old. Chi square test found that the age and cytology of patients in ECC CINⅠ group were statistically different from those of biopsy CINⅠ group (all P<0.05). There was no significant difference in HR-HPV detection, TZ type and colposcopy impression between the two groups (all P>0.05). ECC CINⅠ comprised 957 women, with LEEP histopathology results revealing 288 (30.1%, 288/957) CINⅡ +, which was significantly higher than that of biopsy CINⅠ which was comprised 1 624 women, with LEEP histopathology results showing 333 (20.5%, 333/1 624) CINⅡ + ( χ2=30.31, P<0.001). (2) Compared by LEEP CINⅡ + with LEEP ≤CINⅠ group, there were no significant difference in the age, HR-HPV, colposcopy impression (all P>0.05); but there were significantly differences in cytology, ECC CINⅠ, type Ⅲ TZ (all P<0.001). Multivariate logistic regression analysis showed that atypical squamous epithelial cells (ASC-H; OR=2.77, 95% CI: 2.04-3.77), high-grade squamous intraepithelial lesions and worse (HSIL +; OR=2.93, 95% CI: 2.24-3.81), ECC CINⅠ ( OR=1.89, 95% CI: 1.56-2.29) and type Ⅲ of TZ ( OR=1.76, 95% CI: 1.45-2.11) were independent risk factors for LEEP CINⅡ + (all P<0.05). (3) When cytology was ≤low-grade squamous intraepithelial lesion (LSIL) and ≥ASC-H, the detection rate of CINⅡ + in ECC CINⅠ was significantly higher than that of biopsy CINⅠ (all P<0.001). In ECC CINⅠ, the rate of CINⅡ + with cytology ≤LSIL was significantly lower than that in cytology ≥ASC-H (56.0% vs 25.9%; χ2=49.38, P<0.001). In type Ⅰ/Ⅱ of TZ, the detection rate of CINⅡ + between ECC CINⅠand biopsy CINⅠ had no significantly different; while in type Ⅲ of TZ, there was significantly different (72.7% vs 46.2%; χ2=4.02, P=0.045). In ECC CINⅠ, type Ⅲof TZ was significantly higher in the rate of CINⅡ + than that of type Ⅰ/Ⅱ of TZ (72.7% vs 21.7%; χ2=16.38, P<0.001). When cytology ≥ASC-H, type Ⅲ of TZ and colposcopy impression of HSIL were combined, the rate of CINⅡ + in ECC CINⅠ was 6/6 while 1/3 in biopsy CINⅠ. Conclusions:Cytology ≥ASC-H, ECC CINⅠ and type Ⅲ TZ are the risk factors of LEEP CINⅡ +. However, cytology ≥ASC-H is more valuable in predicting LEEP CINⅡ + than ECC CINⅠ. For patients with ECC CINⅠ to perform LEEP, it is recommended that cytology ≥ASC-H is taken as the first level stratification, and type Ⅲ TZ is taken as the second level stratification. The colposcopy impression of patients is recommended for a reference parameter.

Objective To explore the job satisfaction of the staff in Pharmacy Intravenous Admixture Services (PIVAS), and analyze its status quo and influencing factors. Methods From March to May 2018, totally 105 PIVAS subjects were selected from 4 Class Ⅲ Grade A teaching hospitals in Harbin by random sampling and investigated with Minnesota Satisfaction Questionnaire (MSQ) for their job satisfaction. Data were collected through questionnaire survey, and the influencing factors to the job satisfaction was analyzed. Totally 105 questionnaires were distributed in this survey, and 98 valid questionnaires were recovered, accounting for an effective recovery rate of 93.33％. Results The overall standardized score of MSQ in the 98 PIVAS staff was (4.09±0.57), including (4.13±0.59) for internal satisfaction and (4.03±0.65) for external satisfaction, and the difference was statistically significant (t=2.217,P < 0.05). Multivariate linear regression analysis revealed that marital status and working years were the influencing factors of job satisfaction of the PIVAS staff. Conclusions The external satisfaction of the PIVAS staff is lower than their internal satisfaction, and the satisfaction of married and veteran employees is relatively low. It is recommended that the managers of PIVAS should actively handle the relationship between staff and focus on the job satisfaction of the married staff and staff with long working years.

Objective:To explore the value of contrast-enhanced ultrasound(CEUS) in distinguishing of renal oncocytoma(RO) and chromophobe renal cell carcinoma(chRCC).Methods:The ultrasonic image features of 49 ROs and 72 chRCCs between October 2007 and January 2020 were retrospectively analyzed, all lesions underwent ultrasonic examination (including 19 ROs and 70 chRCCs with CEUS imaging) and were pathologically approved in our institution. The statistically significant parameters from univariate analyses were then entered for further multivariable Logistic regression. The value of each ultrasonic imaging feature in differentiating RO and chRCC was evaluated.Results:According to the univariate analyses, all imaging features on conventional ultrasound were not statistically different between RO and chRCC (all P>0.05), while the characteristics of tumor wash-in/out pattern, enhancement degree and homogeneity at peak time and pseudocapsule around tumor were significantly different (all P<0.05). After multivariable analyses, tumor wash-in and wash-out pattern were excluded for tumor differentiation ( P>0.05), and the parameters of enhancement degree or homogeneity at peak time and pseudocapsule around tumor were still significantly different between tumor types (all P<0.05, odd ratio was 8.683, 6.667 and 18.774 respectively). The overall sensitivity, specificity and accuracy of these three parameters in diagnosing RO was 68.4%, 91.4% and 86.5%, respectively. Conclusions:CEUS can provide some useful information for the differentiation of RO and chRCC.