OBJECTIVES: To investigate the association of HOTAIR gene rs920778 single nucleotide polymorphism (SNP) with breast cancer susceptibility and response to HER2-targeted therapy in a Chinese population. METHODS: TaqMan probe-based real-time quantitative PCR was used for genotyping of the rs920778 locus (chr12:54,376,218) in peripheral blood genomic DNA from 287 breast cancer patients and 260 healthy individuals from northern Anhui Province. The genotype (GG, GT and TT) and allele (G/T) distribution frequencies were compared between the two groups to evaluate their association with breast cancer risk. Multivariate logistic regression analysis was conducted to assess the relationship between SNP at this locus and aggressive clinicopathological features (including tumor size, lymph node metastasis, ER/PR/HER2 status, and molecular subtypes) of breast cancer. For the HER2-positive subgroup, the association between rs920778 genotype and responses to dual-targeted therapy (trastuzumab [6 mg/kg q3w]+pertuzumab [420 mg q3w] + docetaxel [75 mg/m²]) was analyzed. The primary endpoints included pathological complete response rate (pCR), objective response rate (ORR), and progression-free survival (PFS). RESULTS: The TT genotype of rs920778 was associated with a significantly increased breast cancer susceptibility (OR=1.54, 95% CI: 1.09-2.19; P=0.017), an advanced tumor stage (P<0.001), lymph node metastasis (P<0.001), and the triple-negative subtype (P<0.001). In HER2-positive patients, TT genotype carriers had a markedly reduced objective response rate to dual HER2-targeted therapy (33.3% vs 89.3%, P=0.001) and a lower pathological complete response rate after neoadjuvant therapy (P=0.018). CONCLUSIONS The TT genotype of HOTAIR rs920778 serves as an independent risk factor for breast cancer susceptibility and aggressive progression in Chinese population and may predict the resistance to HER2-targeted therapies, suggesting its potential as a prognostic biomarker for precision oncology.
Adult ; Aged ; Female ; Humans ; Middle Aged ; Breast Neoplasms/drug therapy* ; Case-Control Studies ; China ; Drug Resistance, Neoplasm/genetics* ; Genetic Predisposition to Disease ; Genotype ; Polymorphism, Single Nucleotide ; Receptor, ErbB-2 ; RNA, Long Noncoding/genetics* ; East Asian People/genetics*

Patients with severe trauma require an extremely timely treatment and transfusion plays an irreplaceable role in the emergency treatment of such patients. An increasing number of evidence-based medicinal evidences and clinical practices suggest that patients with severe traumatic bleeding benefit from early transfusion of low-titer group O whole blood or hemostatic resuscitation with red blood cells, plasma and platelet of a balanced ratio. However, the current domestic mode of blood supply cannot fully meet the requirements of timely and effective blood transfusion for emergency treatment of patients with severe trauma in clinical practice. In order to solve the key problems in blood supply and blood transfusion strategies for emergency treatment of severe trauma, Branch of Clinical Transfusion Medicine of Chinese Medical Association, Group for Trauma Emergency Care and Multiple Injuries of Trauma Branch of Chinese Medical Association, Young Scholar Group of Disaster Medicine Branch of Chinese Medical Association organized domestic experts of blood transfusion medicine and trauma treatment to jointly formulate Chinese expert consensus on blood support mode and blood transfusion strategies for emergency treatment of severe trauma patients ( version 2024). Based on the evidence-based medical evidence and Delphi method of expert consultation and voting, 10 recommendations were put forward from two aspects of blood support mode and transfusion strategies, aiming to provide a reference for transfusion resuscitation in the emergency treatment of severe trauma and further improve the success rate of treatment of patients with severe trauma.

Background The incidence of Legionnaires' disease is increasing globally and artificial water environment is becoming a common source of outbreaks. Molecular typing techniques can help prevent and control Legionella. Objective To understand the molecular epidemiological characteristics of Legionella pneumophila in artificial water environment of Shanghai hospitals, and provide a scientific basis for the prevention and control of Legionnaires' disease. Methods Water samples were collected from artificial water environment in 14 hospitals from May to October each year from 2019 to 2020 in Shanghai. A total of 984 water samples were collected from 8 Grade-A tertiary hospitals and 6 non-Grade-A tertiary hospitals, including 312 samples of cooling water, 72 samples of chilled water, and 600 samples of tap water. The water samples were isolated and serotyped for Legionella pneumophila and preserved, and the positive rate of Legionella pneumophila in the samples was used as an indicator of contamination. The preserved strains were resuscitated and 81 surviving strains were obtained for pulsed field gel electrophoresis (PFGE) typing analysis. Results A total of 124 Legionella pneumophila positive water samples were detected, with a positive rate of 12.60%. The positive rate was higher in the Grade-A tertiary hospitals (16.54%, 87/526) than in the non-Grade-A tertiary hospitals (8.08%, 37/458) (χ²=15.91, P<0.001). The positive rate of cooling water (23.40%) was the highest among different types of water samples, and the difference was statistically significant (χ²=61.19, P<0.001). The difference in positive rate of tap water was statistically significant among different hospital departments (χ²=11.37, P<0.05). The positive rate in 2019 (15.06%) was higher than that in 2020 (9.84%) (χ²=6.23, P<0.05). From May to October, August had the highest annual average positive rate (16.46%) and October had the lowest (8.54%), but the difference in positive rates among months was not statistically significant (χ²=5.39, P=0.37). The difference in positive rate among districts was statistically significant (χ²=24.88, P<0.001). A total of 131 strains of Legionella pneumophila were isolated, with serotype 1 (80.15%, 105/131) predominating. Among the 81 surviving strains of Legionella pneumophila subjected to PFGE typing, the band-based similarity coefficients ranged from 41.30% to 100%. Among the 29 PFGE band types (S1-S29) recorded, each band type included 1-10 strains, and S28 was the dominant band type. Four clusters (I-IV) of PFGE band types were identified, accounting for 66.67% (54/81) of all strains and containing 13 band types. Conclusion Legionella pneumophila contamination is present in the artificial water environment of hospitals in Shanghai from 2019 to 2020, and the contamination in tap water deserves attention. The detected serotype of Legionella pneumophila is predominantly type 1, and PFGE typing reveals the presence of genetic polymorphism. Therefore, the monitoring and control of Legionella pneumophila in hospital artificial water environment should be strengthened.

Organoid models are used to study kidney physiology, such as the assessment of nephrotoxicity and underlying disease processes. Personalized human pluripotent stem cell-derived kidney organoids are ideal models for compound toxicity studies, but there is a need to accelerate basic and translational research in the field. Here, we developed an automated continuous imaging setup with the "read-on-ski" law of control to maximize temporal resolution with minimum culture plate vibration. High-accuracy performance was achieved: organoid screening and imaging were performed at a spatial resolution of 1.1 μm for the entire multi-well plate under 3 min. We used the in-house developed multi-well spinning device and cisplatin-induced nephrotoxicity model to evaluate the toxicity in kidney organoids using this system. The acquired images were processed via machine learning-based classification and segmentation algorithms, and the toxicity in kidney organoids was determined with 95% accuracy. The results obtained by the automated "read-on-ski" imaging device, combined with label-free and non-invasive algorithms for detection, were verified using conventional biological procedures. Taking advantage of the close-to-in vivo-kidney organoid model, this new development opens the door for further application of scaled-up screening using organoids in basic research and drug discovery.
Humans ; Kidney ; Organoids ; Pluripotent Stem Cells

Objective:To develop and validate a useful predictive model for large gestational age (LGA) in pregnancy using a machine learning (ML) algorithm and compare its performance with the traditional logistic regression model.Methods:Data were obtained from the National Free Preconception Health Examination Project in China, carried out in 220 counties of 31 provinces from 2010 to 2012, covering all rural couples with a planned pregnancy. This study included all teams of childbearing age who delivered newborns within 24-42 weeks of gestational age and their newborns. Ten different ML algorithms were used to establish LGA prediction models, and the prediction performance of these models was evaluated.Results:A total of 104 936 newborns were included, including 54 856 boys (52.3%) and 50 080 girls (47.7%). The incidence of LGA was 11.7% (12 279). The imbalance between the two groups was addressed by the under- sampling technique, after which the overall performance of the ML models was significantly improved. The CatBoost model achieved the highest area under the receiver-operating-characteristic curve (AUC) value of 0.932. The logistic regression model had the worst performance, with an AUC of 0.555.Conclusions:In predicting the risk for LGA in pregnancy, the ML algorithms outperform the traditional logistic regression method. Compared to other ML algorithms, CatBoost could improve the performance, and it deserves further investigation.

ObjectiveTo investigate the effect of the Yap1 gene and tanshinone ⅡA on the proliferation, migration, and invasion abilities of Huh-7 hepatoma cells. MethodsA total of 10 pairs of human hepatocellular carcinoma (HCC) samples and adjacent tissue samples were collected in Zhongnan Hospital of Wuhan University from June 1 to December 1, 2019. Quantitative real-time PCR and Western blotting were used to measure the expression of the Yap1 gene and phenotype-related molecules. MTT cell proliferation detection reagent was used to measure the inhibition rate of cell proliferation after the treatment with different concentrations of tanshinone ⅡA. Western blotting was used to measure the changes in the expression of apoptosis-and migration-related markers after different interventions. Flow cytometry and Transwell assay were used to measure apoptosis and cell migration and invasion abilities. The data of 375 cases of liver cancer and 50 cases of relatively normal liver tissue samples were downloaded from The Cancer Genome Atlas, including clinicopathological information. The t-test was used for comparison of continuous data between two groups, and the chi-square test was used for comparison of categorical data between two groups. ResultsIn 8 of the 10 pairs of HCC samples and adjacent tissue samples, HCC samples had significantly higher expression of Yap1 than the adjacent tissue samples. Compared with the normal human liver epithelial cells L02, the Huh-7 and HCCL-M3 hepatoma cells had a significant increase in the expression of Yap1. The silencing efficiency of si-Yap1-3 transfection reached 87.004% at the protein level. MTT results showed that tanshinone ⅡA effectively inhibited the proliferation of Huh-7 cells, with a half inhibitory concentration of 8.683 μmol/L. After the cells were treated with si-Yap1-3 and tanshinone ⅡA, there was an increase in the expression of the downstream marker for proliferation and migration E-cadherin and a reduction in the expression of vimentin, and the results of Transwell assay showed that compared with the si-NC group, the tanshinone ⅡA+si-Yap1-3 group had significant reductions in the migration and invasion abilities of Huh-7 cells (migration: 43.19±2.88 vs 132.20±10.03, t=8.527, P=0.001; invasion: 53.95±4.20 vs 179.10±11.11, t=4.484, P=0.011). The group treated with si-Yap1-3 and tanshinone ⅡA had an increase in the expression of the apoptosis-related marker Bax and a reduction in the expression of Bcl-2, as well as a significantly higher early apoptosis rate than the si-NC group (2598% vs 9.21%, χ2=4.078, P＜0.05). ConclusionOncogene Yap1 silencing combined with tanshinone ⅡA can promote the apoptosis of Huh-7 hepatoma cells and inhibit their migration and invasion, which can provide certain guiding significance for clinical medication.

Objective:To investigate the effect of natural hyperoxic environment on liver lipid metabolism and liver function based on the bile acid-farnesoid X receptor pathway in sub-healthy rats.Methods:Forty adult male Wistar rats were randomly divided into control group ( n = 10) and sub-healthy model group ( n = 30). The control group was fed a normal diet, and the model group was fed a high-fat-sugar diet with limited daily activities for 5 weeks. The sub-healthy model was successfully established and the feeding conditions were restored. The hyperoxic intervention group (healthy group) were placed in a natural hyperoxic environment for 7 days. The rats feeding status in the spontaneous recovery group were unchanged. The appearance and exhaustive swimming time were compared before and after in healthy rats. Peripheral blood was collected for biochemical measurement. The fluorescence intensity of FXR and peroxisome proliferator activated receptor α (PPAR α) in liver tissue was detected by fluorescence double staining. Real-time fluorescent semi-quantitative PCR and Western blot were used to detect the RNA and protein expression condition of bile acid-FXR signaling pathway related indicators (FXR, PPARα, and SREBP-1c) in liver tissues. Results:Compared with the control group, the model group had gained body weight, and the vitality was decreased, while triglycerides [TG, (1.18 ± 0.20) mmol/L vs. (0.65 ± 0.12) mmol/L] and total cholesterol [TC, (1.23 ± 0.29) mmol/L vs. (1.00 ± 0.25) mmol/L] level was increased, ( P < 0.05), which suggests the presence of hepatic steatosis. TG and TC level in the healthy group and spontaneous recovery group were lower than the model group, and the differences between the healthy group and the model group were statistically significant ( P < 0.05). Compared with the model group, the expression of FXR and PPARα in the liver of the healthy and the spontaneous recovery group was enhanced, while the expression of the sterol regulatory element binding protein 1c (SREBP-1c) was decreased. FXR and PPARα mRNA levels in the healthy group and the model group were (9.27 ± 0.26 vs. 6.77 ± 0.20), and (9.71 ± 0.21 vs. 7.09 ± 0.24), P < 0.01, respectively. Compared with the model group, spontaneous recovery group mRNA levels were 7.99 ± 0.30 and 8.44 ± 0.28, P < 0.05, respectively. FXR and SREBP-1c protein levels between the healthy group and the model group were (1.30 ± 0.19 vs.0.43 ± 0.28), and (1.56 ± 0.22 vs. 2.43 ± 0.19), P < 0.01, respectively. Compared with the model group, the FXR and SREBP-1c protein levels of the spontaneous recovery group were 0.81 ± 0.33 vs. 2.10 ± 0.38, P < 0.05, respectively. In addition, natural hyperoxic environment had enhanced liver lipid metabolism and improved lipid disorders. Conclusion:The natural hyperoxic environment have the ability to regulate liver lipid metabolism and can improve mild hyperlipidemia to a certain extent.

Objective:To investigate the MRI features of hepatic nodular regenerative hyperplasia (NRH) induced by chemotherapy.Methods:The clinical data and MRI of 20 cases with hepatic NRH induced by chemotherapy and confirmed by pathology in Zhongshan Hospital Fudan University from August 2014 to May 2019 were retrospectively analyzed. There were 13 males and 7 females, with an average age of 49.8 ± 9.7 years. Contrast-enhanced MR scan with Gd-DTPA was performed eighteen patients, and two patients underwent contrast-enhanced MR scan with hepatobiliary specific contrast (Gd-EOB-DTPA). The image analysis includes the number, location, size, shape, signal intensity in plain scan and enhancement pattern of lesions. The apparent diffusion coefficient (ADC) values of the lesions and adjacent hepatic parenchyma were measured on the ADC map, and the difference was compared with paired sample t test.Results:A total of 36 lesions in 20 patients were rounded or oval, including 23 (63.9%) lesions in the right lobe, 12 (33.3%) in the left lobe and 1 (2.8%) in the caudate lobe. The average diameter of all lesions was 15.4 ± 6.4 (7.0-37.0) mm. The boundary was clear in 9 (25.0%) lesions and blurred in 27 (75%) lesions. In T1WI, 35 (97.2%) lesions showed slightly hypointensity, and in 1 (2.8%) lesion was iosintensity. All 36 lesions showed slightly hyperintensity in T2WI. 33 (91.7%) lesions showed slightly hyperintensity in DWI, and 3 (8.3%) lesions showed iosintensity. 31 lesions with Gd-DTPA enhanced MR scan were significantly enhanced in the arterial phase and showed slightly high signal intensity in early portal vein phase, late portal vein phase and equilibrium phase. 5 lesions with Gd-EOB-DTPA enhanced MR scan were also significantly enhanced in the arterial phase and showed slightly high signal intensity in early portal vein phase, late portal vein phase and equilibrium phase, then all lesions showed circular high signal intensity in hepatobiliary specific phase. The average ADC value of 29 lesions was (1.471 ± 0.253) × 10 -3 mm 2/s, and that of adjacent liver parenchyma was (1.460 ± 0.235) ×10 -3 mm 2/s. There was no significant difference between the two groups ( P > 0.05). Conclusion:MR findings of NRH induced by chemotherapy have certain characteristics, and the morphological manifestations, diffusion-weighted imaging, enhanced imaging and hepatobiliary specific phase features of the lesions can help to diagnose the disease.

Objective:To analyze the clinical data on hospitalized spinal cord injury patients with calf muscle vein thromboses (MCVTs) seeking prevention and treatment techniques.Methods:The medical records of 423 patients with spinal cord injury were collected. Those with MCVT constituted the observation group, while those without served as controls. Their clinical data were compared.Results:The risk factors for MCVT were screened in logistic regression analyses. The results showed that age, an ASIA grade of A or B, spinal fusion, preventive anticoagulation, physiotherapy treatment and a homocysteine level >15μmol/L were risk factors for the occurrence of a MCVT.Conclusions:Age, an ASIA grade of A or B, spinal fusion or an elevated serum homocysteine level are all risk factors for MCVT. Active anticoagulation and physical therapy may reduce the risk.

Objective: To investigate the interventional effect of bicyclol on isoniazid-induced liver injury in rats and the expression of endoplasmic reticulum stress (ERS) protein, glucose regulatory protein 78 (GRP78), and growth arrest and DNA-damage-inducible gene 153(CHOP). Methods: Eighty Wistar rats were randomly divided into control group (8 rats) and model group (72 rats). After 10 days of intragastric administration of isoniazid, the model group rats were randomly divided into treatment group (A), natural recovery group (B), etiological persistence group (C) and etiological persistence plus treatment group (D). Sixteen rats from each group were sacrificed after 1 and 2 weeks of intervention with different methods. Serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were detected. Liver pathological morphology was observed. Apoptotic cells were detected by TUNEL assay. ERS protein expression was detected by Western blot. A t-test or randomized block analysis of variance, K-S test and Levene’s test were used to analyze the normality and homogeneity of variance. Kruskal-Wallis rank sum test was used for data that did not suit the conditions of t-test and variance analysis. Results: ALT and AST were elevated in the model group, and liver pathological examination showed liver tissue damage. Apoptotic index was higher than control group (7.13% ± 1.55% vs. 0.75% ± 0.71%, Z = -3.411, P < 0.01), and the expression value of ERS protein in model group was significantly higher than control group (GRP78: 1.16 ± 0.30 vs. 0.23 ± 0.05, t = -6.008, P < 0.01; CHOP: 0.98±0.23 vs. 0.20 ± 0.10, t = -6.378, P < 0.01). Serum enzymes, apoptotic index and ERS protein expressions of rats were decreased after treatment with bicyclol, and the pathological damage was eased. Rats in natural recovery group recovered less than the treatment group. Conclusion Isoniazid-induced liver injury is associated to ERS-related excessive apoptosis and the therapeutic effect of bicyclol on drug-induced liver injury may minimize ERS-induced apoptosis.