Objective To analyze the virus subtypes, molecular evolutional and molecular transmission network features of the first confirmed mpox case in Huai’an City, Jiangsu Province, so as to provide insights into understanding of the transmission and evolution dynamics of mpox virus and formulation of the mpox control strategy in the city. Methods Genomic DNA was extracted from swabs of the first confirmed mpox case’s skin lesions in Huai’an City, and the amplicon sequencing library was constructed using the hypersensitive mpox virus whole-genome capture kit. High-throughput sequencing was performed using the GridION X5 nanopore sequencer on the Nanopore sequencing platform, and single nucleotide polymorphism (SNP) analysis of mpox virus genome sequences was performed following sequence assembly. In addition, phylogenetic analysis, genetic genealogy and molecular traceability analysis were performed. Results The virus whole genome sequence of the first confirmed mpox case was successfully obtained by high-throughput sequencing, with a full length of 197 182 bp, and was named hMpxV/China/JS-HA01/2023, which belonged to the clade IIb (West African clade) lineage B.1.3. Compared with the mpox virus reference sequence MPXV-M5312_HM12_Rivers-001 (GenBank accession number: NC_063383), the genome sequence of the Huai’an virus isolate carried 86 SNPs, including 40 SNPs in the coding region as non-synonymous mutations and 73 SNPs as nucleotide mutations caused by APOBEC3 (APOBEC3). Of the 97 mpox virus gene sequences, 79 sequences were included in the molecular network (81.44%), and the threshold of the genetic distance accessed to the network was 0.35/10⁵. There were two large molecular transmission clusters and one scattered cluster in the molecular transmission network of the mpox virus, andthehMpxV/China/JS-HA01/2023 sequence was located in the large cluster. The 97 gene sequences formed 92 haplotypes, including three shared haplotypes Hap_4, Hap_6 and Hap_38, and an exclusive haplotype Hap_1 of hMpxV/China/JS-HA01/2023 generated from mutation of the exclusive haplotype Hap_43, while the exclusive haplotype Hap_43 was generated from mutation of the shared haplotype Hap_38. Conclusions The whole genome sequence of the mpox virus isolated from the first confirmed mpox case in Huai’an City has been successfully obtained, and the molecular evolutionary and molecular transmission network characteristics of the virus have been preliminarily understood.

Objective:To evaluate the efficacy of cerebral-placental-uterine ratio(CPUR)in predicting late-on-set fetal growth restriction(FGR).Methods:From May 2020 to May 2021,1255 women with singleton pregnancy who underwent prenatal examinations at the University of Hong Kong Shenzhen Hospital were selected for fetal growth and Doppler measurements at 35-37 +6 weeks of gestation.Pregnant women with birth weight of newbo-rns＜the 10th percentile were the FGR group.The pulsatility index(PI)of uterine artery(UtA),umbilical artery(UA)and fetal middle cerebral artery(MCA)were analyzed separately and in combination.ROC curve was used to analyze the cerebral-placental-uterine ratio(CPUR),cerebral-placental ratio(CPR),cerebral-uterine ratio(C-UtA)for predicting late-onset FGR;and to evaluate the sensitivity,positive and negative predictive value and of CPUR in the prediction of late-onset FGR.Results:The area under the curve(AUC)of CPUR,CPR,C-UtA and mean UtA-PI for FGR grope were 0.88,0.86,0.84 and 0.72.Under certain cut-off values and 87% specificity,the specificity of CPUR,CPR,C-UtA and mean UtA-Pifor predicting FGR group was 43.2%,46.6%,39.8% and 23.9%,respectively.The positive predictive values of CPUR,CPR,C-UtA and mean UtA-PI,UA-PI for predicting FGR group were 90.5%,71.9%,83.3%,63.6%and 5.2%,respectively.Conclusions:CPUR is more effective in predicting late onset FGR than CPR,C-UtA and mean UtA-PI.It can effectively increase the detection rate of fetal growth restrictionand reduce the FGR risk.

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.

Objective:To construct a novel chimeric antigen receptor T (CAR-T) cell targeting CD138 and to investigate its cytotoxicity against myeloma cells.Methods:The hybridoma strain that can stably secrete the CD138 monoclonal antibody (mAb) was prepared and obtained through monoclonal antibody screening technology. The hybridoma strain cells were intraperitoneally injected into mice to produce ascites containing monoclonal antibodies, which were then collected and purified to obtain pure CD138 mAb. Further examinations were performed to assess the biological characteristics of CD138 mAb. The variable region sequence of this antibody was amplified through reverse transcription polymerase chain reaction and was used as the antigen recognition domain of CD138 CAR, which was subsequently expressed on the surface of T cells by lentiviral infection. Flow cytometry was employed to assess the phenotype of CD138 CAR-T cells. In vitro cytotoxicity and degranulation assays were performed to evaluate their antitumor effects.Results:① We successfully prepared anti-human CD138 antibody hybridoma cell lines and screened a hybridoma cell strain, 5G2, which could persistently and stably secrete the anti-CD138 antibody. ② The purified CD138 (5G2) mAb can especially recognize CD138 + cells with a binding affinity constant (K D) of 6.011×10 -9 mol/L and showed no significant binding activity with CD138 - cells. ③The variable region sequence of the CD138 (5G2) antibody was obtained using molecular cloning technology, and CD138 (5G2) CAR was successfully constructed and expressed on T cells through lentivirus infection and, concurrently, demonstrated effective binding to recombinant human CD138 protein.④ The proliferation of T cells transduced with the CD138 (5G2) CAR was highly efficient. The phenotype analysis revealed that CD138 (5G2) CAR-T cells exhibited a greater tendency to differentiate into central memory T cells and memory stem T cells, with a reduced proportion of terminally differentiated effector memory subsets. ⑤CD138 (5G2) CAR-T cells demonstrated specific cytotoxicity against CD138 + myeloma cell line H929, whereas CD138 - cell line K562 remained unaffected. The percentage of residual H929 cells was (12.92±8.02) % after co-culturing with CD138 (5G2) CAR-T cells, while (54.25±15.79) % was left in the Vector-T group (E∶T=1∶2; P<0.001). ⑥Results of degranulation assays demonstrated a significant activation of CD138 (5G2) CAR-T cells after co-culture with the H929 cell line, whereas no significant activation was observed in Vector-T cells [ (25.78±3.35) % vs (6.13±1.30) %, P<0.001]. ⑦After co-culturing with CD138 + cells, CD138 (5G2) CAR-T cells exhibited a significant increase in cytokine secretion compared to the Vector-T group [interleukin-2: (1 697.52±599.05) pg/ml vs (5.07±1.17) pg/ml, P<0.001; interferon-γ: (3 312.20±486.38) pg/ml vs (9.28±1.46) pg/ml, P<0.001; and tumor necrosis factor-α: (1 837.43±640.49) pg/ml vs (8.75±1.65) pg/ml, P<0.001]. However, no significant difference was observed in cytokine secretion levels between the two groups after co-culturing with CD138 - cells. Conclusion:This study successfully prepared a novel monoclonal antibody against CD138, and CAR-T cells constructed with the antigen recognition domain derived from this 5G2 mAb demonstrated effective antitumor activity against myeloma cells. This can be used as a new option for the detection of the CD138 antigen and proposes a novel strategy for multiple myeloma immunotherapy.

OBJECTIVES: Graves' ophthalmopathy (GO) is a multifactorial disease, and the mechanism of non coding RNA interactions and inflammatory cell infiltration patterns are not fully understood. This study aims to construct a competing endogenous RNA (ceRNA) network for this disease and clarify the infiltration patterns of inflammatory cells in orbital tissue to further explore the pathogenesis of GO. METHODS: The differentially expressed genes were identified using the GEO2R analysis tool. The Kyoto encyclopedia of genes and genomes (KEGG) and gene ontology analysis were used to analyze differential genes. RNA interaction relationships were extracted from the RNA interactome database. Protein-protein interactions were identified using the STRING database and were visualized using Cytoscape. StarBase, miRcode, and DIANA-LncBase Experimental v.2 were used to construct ceRNA networks together with their interacted non-coding RNA. The CIBERSORT algorithm was used to detect the patterns of infiltrating immune cells in GO using R software. RESULTS: A total of 114 differentially expressed genes for GO and 121 pathways were detected using both the KEGG and gene ontology enrichment analysis. Four hub genes (SRSF6, DDX5, HNRNPC,and HNRNPM) were extracted from protein-protein interaction using cytoHubba in Cytoscape, 104 nodes and 142 edges were extracted, and a ceRNA network was identified (MALAT1-MIR21-DDX5). The results of immune cell analysis showed that in GO, the proportions of CD8⁺ T cells and CD4⁺ memory resting T cells were upregulated and downregulated, respectively. The proportion of CD4 memory resting T cells was positively correlated with the expression of MALAT1, MIR21, and DDX5. CONCLUSIONS This study has constructed a ceRNA regulatory network (MALAT1-MIR21-DDX5) in GO orbital tissue, clarifying the downregulation of the proportion of CD4⁺ stationary memory T cells and their positive regulatory relationship with ceRNA components, further revealing the pathogenesis of GO.
Humans ; CD8-Positive T-Lymphocytes ; RNA, Long Noncoding/genetics* ; Algorithms ; CD4-Positive T-Lymphocytes ; Down-Regulation ; Graves Ophthalmopathy/genetics* ; Gene Regulatory Networks ; MicroRNAs/genetics* ; Serine-Arginine Splicing Factors ; Phosphoproteins

[This corrects the article DOI: 10.1016/j.apsb.2022.06.009.].

Objective:To investigate the association of non-high-density lipoprotein cholesterol (non-HDL-C) level with non-alcoholic fatty liver disease (NAFLD) in patients with early-onset type 2 diabetes.Methods:The clinical data of 100 patients with early-onset type 2 diabetes who were admitted to Beijing Chaoyang Diabetes Hospital from June 2008 to June 2012 were retrospectively analyzed. These patients were divided into a NAFLD group and a non-NAFLD group, with 50 patients in each group, according to the presence or absence of NAFLD. Clinical data, biochemical indices [blood lipids, blood glucose, liver function, uric acid, high-sensitivity C-reactive protein], and glycosylated hemoglobin were collected. Body mass index and non-HDL-C levels were recorded. The association of non-HDL-C level with NAFLD in patients with early-onset type 2 diabetes was analyzed using logistic regression analysis. The predictive value and optimal cut-off point of non-HDL-C for early-onset T2 diabetes complicated by NAFLD were evaluated using the receiver operating characteristic curve.Results:Body mass index, waist-to-hip ratio, systolic blood pressure, and diastolic blood pressure in the NAFLD group were (28.55 ± 3.47) kg/m 2, (0.94 ± 0.05), (121.00 ± 10.25) mmHg (1 mmHg = 0.133 kPa), and (80.00 ± 8.51) mmHg respectively, which were significantly higher than (23.95 ± 2.87) kg/m 2, (0.90 ± 0.07), (115.20 ± 13.36) mmHg, and (73.70 ± 7.75) mmHg in the non-NAFLD group ( t = -7.23, -3.11, -2.44, -3.87, all P < 0.05). Non-HDL-C, total cholesterol, triglyceride, low-density lipoprotein cholesterol, alanine aminotransferase, aspartate aminotransferase, γ-glutamyl transpeptidase, uric acid, high-density lipoprotein cholesterol, and glycosylated hemoglobin levels in the NAFLD group were (4.88 ± 3.01) mmol/L, (6.33 ± 3.23) mmol/L, (4.50 ± 6.03) mmol/L, (3.27 ± 1.26) mmol/L, (39.80 ± 23.58) U/L, (27.72 ± 13.83) U/L, (52.96 ± 46.16) U/L, (350.32 ± 102.12) μmol/L, (1.26 ± 0.88) mg/L, and (9.3 ± 2.5)%, respectively, which were significantly higher than (3.35 ± 1.03) mmol/L, (4.81±1.24) mmol/L, (1.87 ± 2.29) mmol/L, (2.70 ± 0.71) mmol/L, (23.76 ± 13.45) U/L, (21.98 ± 10.13) U/L, (35.24 ± 35.41) U/L, (296.04 ± 88.26) μmol/L, (0.22 ± 1.54) mg/L, (8.2 ± 2.7)% in the non-NAFLD group ( t = -3.40, -3.11, -2.88, -2.81, -4.18, -2.36, -2.14, -2.85, -4.12, -2.08, all P < 0.05). Logistic regression analysis showed that the increase in non-HDL-C level was an independent risk factor for T2 diabetes mellitus complicated by NAFLD ( OR = 3.064, 95% CI: 1.604-5.852, P = 0.001). The receiver operating characteristic curve analysis results showed that the optimal cut-off point, sensitivity, and specificity of non-HDL-C level to predict NAFLD were 3.60 mmol/L, 0.700, and 0.620 respectively. Conclusion:An increase in non-HDL-C level is an independent risk factor for NAFLD complicated by early-onset type 2 diabetes When non-HDL-C is > 3.60 mmol/L, NAFLD can be predicted.

The poor prognosis of triple negative breast cancer (TNBC) results from a lack of approved targeted therapies coupled with aggressive proliferation and metastasis, which is associated with high recurrence and short overall survival. Here we developed a strategy by employing tumor-targeted self-assembled nanoparticles to coordinately regulate BACH1 (BTB domain and CNC homology 1) and mitochondrial metabolism. The BACH1 inhibitor hemin and mitochondria function inhibitor berberine derivative (BD) were used to prepare nanoparticles (BH NPs) followed by the modification of chondroitin sulfate (CS) on the surface of BH NPs to achieve tumor targeting (CS/BH NPs). CS/BH NPs were found to be able to inhibit tumor migration and invasion by significantly decreasing the amounts of tumor cell metabolites, glycolysis and metastasis-associated proteins, which were related to the inhibition of BACH1 function. Meanwhile, decreased mitochondrial membrane potential, activated caspase 3/9 and increased ROS production demonstrated coordinated regulation of BACH1 and mitochondrial metabolism. In a xenograft mice model of breast cancer, CS/BH NPs significantly inhibited tumor growth and metastasis due to the synergetic effect of hemin and BD without showing obvious toxicities for major organs. In sum, the results of efficacy and safety experiments suggest potential clinical significance of the prepared self-assembled CS/BH nanoparticles for the treatment of TNBC.

Objective:To establish a method of serum detection by Raman spectroscopy for the diagnosis of gastric cancer.Methods:Between April and November 2019, 110 patients with gastric cancer [73 males, 37 females, age (57.4±10.3) years] and 74 patients with colorectal cancer [48 males and 26 females, aged (58.3±12.2) years] were collected at the First Affiliated Hospital of Army Military Medical University, along with 100 healthy subjects [59 males and 41 females, aged (55.6±10.61) years] during the same period. Fasting venous blood serum samples were collected from the subjects. A Raman spectrometer XploRA PLUS was used in this experiment, with an excitation light source of 532 nm, a field of view of 100 times, and a spectrum range of 200-2 000 cm -1, etc. The serum samples were detected by nondestructive and non-contact rapid detection, and the Raman spectra of serum samples were collected. Using the Raman spectrum acquisition and processing supporting software LabSpec6 to smooth, baseline, and normalize the obtained Raman spectrum. Multivariate statistical analysis software SIMCA14.1 were applied to import and analyze the obtained Raman spectrum data by principal component analysis (PCA), orthogonal partial least squares discriminant analysis (OPLS-DA), and other methods for statistical analysis. An operating characteristic curve (ROC) was constructed to evaluate the model analysis effect between serum samples of healthy people and those with gastric cancer. Serum samples from the colorectal cancer group were used to verify the reliability of the model. Results:Six Raman peaks with good repeatability were detected in serum samples in health and gastric cancer group, and peaks were located at 1 001.17, 1 154.63, 1 337.89, 1 446.85, 1 515.33, and 1 658.34 cm -1, respectively. Raman intensities at six Raman peaks were significantly different between healthy and gastric cancer groups. At the displacement of 1 001.17, 1 154.63, and 1 515.33 cm -1, the Raman intensity in the healthy group was higher than that in the gastric cancer group. At 1 337.89, 1 446.85, and 1 658.34 cm -1 displacement, the Raman intensity of the gastric cancer group was higher than that of the healthy group. An OPLS-DA model was constructed to analyze the serum samples of the healthy group and the gastric cancer group. In the model, R 2 is the fitting power, and Q 2 is the predictive ability. The closer the values of R 2 and Q 2 are to 1, the better the performance of the model, and the obtained model's R 2X(cum)=0.809, R 2Y(cum)=0.819, Q 2(cum)=0.758. ROC characteristic curve was drawn based on the OPLS-DA model. The area under the curve (AUC) of the gastric cancer group was 0.998. Six peaks with good repeatability were detected in the serum Raman spectra of gastric cancer stage Ⅰ, Ⅱ, Ⅲ, and Ⅳ, which were located at the displacement of 1 001.85, 1 155.07, 1 338.36, 1 445.75, 1 515.92, and 1 657.68 cm -1, respectively, and at the displacement of 1 155.07 and 1 515.92 cm -1. The Raman intensity of gastric cancer stage Ⅳwas significantly higher than that of gastric cancer stages Ⅰ, Ⅱ, and Ⅲ. Conclusions:According to the model reliability verification, the healthy group, gastric cancer group and colorectal cancer group can also be effectively separated based on OPLS-DA results; it showed a good performance in separating the healthy group from the gastric cancer group. It is possible to detect serum samples from healthy people and gastric cancer patients unlabeled by combining Raman spectroscopy and the OPLS-DA method in multivariate statistics.

Objective:To investigate the effects of early Comfort using Analgesics, minimal Sedatives and maximum Humane care (eCASH) patterns on the risk of negative mood and continuous renal replacement therapy (CRRT)-related adverse events in patients with severe CRRT.Methods:A total of 90 patients with severe CRRT in Shenzhen Integrated Traditional Chinese and Western Medicine Hospital from October 2018 to October 2020 were selected as the study subjects, and they were divided into observation group and control group according to random number table method, with 45 patients in each group. The control group was given routine nursing program, and the observation group was given eCASH mode on the basis of the control group.Nursing satisfaction, CRRT-related adverse events and negative mood scores before and after nursing were compared between 2 groups.Results:The nursing satisfaction degree of the observation group was 86.67% (39/45), significantly higher than that of the control group (66.67%, 30/45), and the difference was statistically significant ( χ2=5.03, P<0.05). After nursing, the Hospital Anxiety and Depression Scale-Anxiety(HADS-A) and Hospital Anxiety and Depression Scale-Depression(HADS-D) scores of the observation group were 5.18 ± 0.67 and 5.27 ± 0.61, respectively, lower than 8.14 ± 1.18, 7.94 ± 1.07 before intervention, and 6.33 ± 0.72, 5.94 ± 0.49 of the control group. Barthel Index(BI) (65.17 ± 8.67) was significantly higher than that before nursing 41.56 ± 6.46 and control group 60.48 ± 6.47, the difference was statistically significant ( t values were 5.74-20.76, all P<0.05). The scores of Visual Analogue Scale(VAS), Present Pain Intensity(PPI), sensory total score and emotional total score of observation group after nursing were 3.24 ± 0.56, 1.18 ± 0.25, 6.38 ± 0.89, 2.68 ± 0.59 significantly lower than those before nursing 6.24 ± 0.87, 3.24 ± 0.56, 11.24 ± 1.81, 6.37 ± 1.04 and 4.36 ± 0.67, 1.31 ± 0.31, 7.26 ± 0.96, 2.98 ± 0.62 of the control group. The difference was statistically significant ( t values were 2.19-20.70, P<0.05). Conclusions:eCASH model can significantly improve the negative emotions of patients with severe CRRT, improve their comfort and reduce the risk of related adverse events, which is worthy of clinical promotion.