[Evaluation of the efficacy and safety of intravenous infusion of ferric derisomaltose in the treatment of iron deficiency anemia: a single-center retrospective analysis].

Objective: To investigate the clinical efficacy and safety of ferric derisomaltose injection versus iron sucrose injection in the treatment of iron deficiency anemia (IDA) . Methods: A total of 120 patients with iron deficiency anemia admitted from June 2021 to March 2023 were given intravenous iron supplementation with ferric derisomaltose to assess the efficacy and safety of hemoglobin (HGB) elevation before and after treatment. Simultaneously, the clinical effects of iron supplementation with iron sucrose were compared to those of inpatient patients during the same period. Results: Baseline values were comparable in both groups. Within 12 weeks of treatment, the elevated HGB level in the ferric derisomaltose group was higher than that of the iron sucrose group, with a statistical difference at all time points, and the proportion of HGB increased over 20 g/L in the patients treated for 4 weeks was higher (98.7%, 75.9% ). During the treatment with ferric derisomaltose and iron sucrose, the proportion of mild adverse reactions in the ferric derisomaltose group was slightly lower than that of the iron sucrose group, and neither group experienced any serious adverse reactions. The patients responded well to the infusion treatment, with no reports of pain or pigmentation at the injection site. Conclusion: The treatment of IDA patients with ferric derisomaltose has a satisfactory curative effect, with the advantages of rapidity, accuracy, and safety. Therefore, it is worthy of widespread clinical use.

[Role and clinical significance of MUC4 gene mutations in thrombotic events in patients with classic paroxysmal nocturnal hemoglobinuria].

Objective: This study aimed to investigate the role and clinical significance of MUC4 gene mutations in thrombotic events in patients with classic paroxysmal nocturnal hemoglobinuria (PNH) patients. Methods: A retrospective analysis was conducted on the clinical data and gene sequencing results of 45 patients with classic PNH admitted to the Department of Hematology, Tianjin Medical University General Hospital, from June 2018 to February 2022. MUC4 gene mutations in patients with classic PNH were summarized, and the risk factors for thrombotic events in these patients were analyzed. Additionally, the effects of MUC4 gene mutations on the cumulative incidence and survival of thrombotic events in patients with classic PNH were determined. Results: The detection rate of MUC4 gene mutations in patients with classic PNH who experienced thrombotic events (thrombotic group) was 68.8% (11/16), which was significantly higher than that in the non-thrombotic group [10.3% (3/29) ] (P<0.001). All mutations occurred in exon 2. MUC4 mutation (OR=20.815, P=0.010) was identified as an independent risk factor for thrombotic events in patients with classic PNH. The cumulative incidence of thrombotic events was 78.6% (11/14) in the MUC4 gene mutation group (mutation group) and 16.1% (5/31) in the non-mutation group, showing a statistically significant difference between the two groups (P<0.001). Survival analysis showed a lower overall survival (OS) rate in the thrombotic group compared with that in the non-thrombotic group [ (34.4±25.2) % vs. (62.7±19.3) % ] (P=0.045). The OS rate of patients was (41.7±29.9) % in the mutation group and (59.1±18.3) % in the non-mutation group (P=0.487) . Conclusion: MUC4 gene mutations are associated with an increased incidence of thrombotic events in classic PNH patients, highlighting their role as independent risk factors for thrombosis in this population. These mutations can be considered a novel predictive factor that aids in evaluating the risk of thrombosis in patients with classic PNH.

[Membrane anatomy-based radical resection for esophageal cancer].

Radical resection of gastrointestinal tumors based on the membrane anatomy theory has significantly reduced the postoperative recurrence rate and improved the surgical efficacy. However, the theory of membrane anatomy has not been widely adopted in radical surgery for esophageal cancer. Our study found that the esophagus also has a membranous anatomical structure. As a foregut organ, the esophagus also has a mesenteric structure, and there is also a fifth metastasis pathway within the esophageal mesentery for esophageal cancers. The leak and metastasis of cancer caused by destruction of the mesenteric integrity may be the fundamental reason for the high postoperative recurrence rate. Using the nano carbon and indocyanine green fluorescence tracing technique, we demonstrated the lymphatic drainage of the upper esophageal segment to the left gastric artery mesenteric lymph nodes. Therefore, in the radical resection of esophageal cancer, we used the membrane anatomy theory for guidance to completely remove the esophageal cancer, esophageal mesentery, left gastric artery and its mesentery, as well as all structures within the mesentery, preventing the spread of cancer cells through the blood vessels, lymphatic system, and mesentery, and improving the efficacy and prognosis. This article elaborates on the theoretical basis of the anatomical structure of the esophageal membrane, embryonic development, imaging, autopsy, and endoscopic observation of the structure, as well as the application effect of the esophageal membrane anatomical theory in esophageal cancer radical surgery. It elucidates the anatomical structure of the esophageal membrane and the lymphatic drainage characteristics of esophageal cancer, reveals the law of lymphatic metastasis in esophageal cancer, optimizes lymphatic dissection strategies, and improves the efficacy of esophageal cancer radical surgery.

Cluster of Differentiation 147 (CD147) serves as a promoter of atherosclerosis in patients with cerebral infarction.

OBJECTIVE: The aim of this study was to investigate the correlations of cluster of differentiation 147 (CD147) with plaque stability of carotid atherosclerosis (AS), degree of stenosis, inflammatory factors, matrix metalloproteinase-9 (MMP-9) expression and vascular endothelial function in patients with cerebral infarction. PATIENTS AND METHODS: A total of 50 patients diagnosed with cerebral infarction (cerebral infarction group), 70 patients diagnosed with AS plaque (plaque group, with no infarction but plaques only) and 30 healthy people receiving physical examination (control group) in our hospital from March 2018 to July 2019 were collected. The levels of biochemical indexes, CD147, MMP-9, vascular endothelial function indexes [endothelin-1 (ET-1) and C-reactive protein (CRP)] and inflammatory factors [interleukin-10 (IL-10), IL-16 and tumor necrosis factor-alpha (TNF-α)] in the blood of each group of patients were detected via radioimmunoassay and enzyme-linked immunosorbent assay (ELISA). Moreover, ultrasonic examination and Gensini score system were applied to score the degree of carotid stenosis in cerebral infarction group. Finally, the differences in various parameters were compared among the three groups, and the correlations of CD147 with different indexes were evaluated using Spearman method. RESULTS: Compared with those in control group, the levels of CD147, MMP-9, hemoglobin, platelets, total cholesterol, triglyceride, low-density lipoprotein (LDL), high-density lipoprotein (HDL), apolipoprotein A, apolipoprotein B, IL-10, IL-13 and TNF-α in the blood were remarkably elevated in cerebral infarction group and plaque group (p<0.05). Cerebral infarction group had notably higher levels of CD147, hemoglobin, triglyceride, apolipoprotein B, IL-10, IL-13 and TNF-α in the blood than plaque group (p<0.05). The plaque score was markedly higher in cerebral infarction group than that in plaque group [(3.27±2.86) points vs. (0.93±1.44) points] (p<0.05). In comparison with control group, plaque group and cerebral infarction group exhibited evidently raised levels of blood ET-1 and CRP (p<0.05). The serum CD147 level was significantly associated with MMP-9 (p=0.003, r=0.616), Gensini score (p=0.006, r=0.656), plaque score (p=0.027, r=0.396), IL-10 (p=0.004, r=0.603), TNF-α (p=0.001, r=0.746) and CRP (p=0.037, r=0.450) in cerebral infarction group. CONCLUSIONS: CD147 level is prominently increased in carotid AS and closely related to inflammatory responses, and CD147 may become a new reference for the prediction and treatment of AS and cerebral infarction.

[Analysis of the development status and trend of vaccines in China's immunization program in the past decade].

Vaccines for immunization programs play a pivotal role in the prevention and control of infectious diseases in China. Since the implementation of the Expanded Program on Immunization in 2007, a total of 15 vaccines have been used in the national immunization program, which can prevent 15 kinds of diseases. The development of vaccines in China's immunization program in the past decade is analyzed in terms of variety, quantity, production enterprise, quality standard, and supervision system. The results show that the average dose of vaccines for China's immunization planning is about 570 million doses per year from 2011 to 2020. The overall development of the vaccine industry for immunization planning is stable, and there are between one to five manufacturers for each type of vaccine mainly relying on domestic production. Vaccine quality standards have been continuously improved and are basically consistent with international standards. The vaccine supervision system has been continuously completed and covered the entire process of research and development, production and distribution.

[Clinical application value of peripheral blood metagenomic next-generation sequencing test for patients with hematological diseases accompanied by fever].

Objective: To investigate the clinical application value of peripheral blood metagenomic next-generation sequencing (mNGS) test for patients with hematological diseases accompanied by fever. Methods: The blood mNGS results and clinical data of inpatients with hematological diseases accompanied by fever treated in the Hematology Department of Tianjin Medical University General Hospital in March 2020 to June 2021were retrospectively analyzed. A total of 90 patients with 98 cases of specimens were included. The pathogen distribution characteristics and mNGS test performance were analyzed. Results: The positive rate of peripheral blood mNGS was significantly higher than that of traditional examination (68.37% vs 37.76%, P<0.001) and blood culture (68.37% vs 9.18%, P<0.001) . Viral, bacterial, and fungal infections accounted for 38.81%, 14.93%, and 2.99% in patients with single-pathogen infections, respectively. Polymicrobial infections accounted for 43.28%, in which viral and bacterial coinfections were the most common type (25.37%) . There were 55 virus-positive cases (82.09%) , 30 bacteria-positive cases (44.78%) , and 14 fungus-positive cases (20.90%) . The clinical approval rate of peripheral blood mNGS was 64.63% (63/98) . The sensitivity, specificity, positive predictive value, and negative predictive value (NPV) of peripheral blood mNGS were 75.68%, 36.07%, 41.79%, and 70.97%, respectively, and the overall consistency rate with traditional examination was 51.02%. Of the 22 pulmonary infection cases with no detectable pathogens by conventional tests, the pathogens were identified by peripheral blood mNGS in 14 cases, 10 of which were clinically approved. Conclusion: The positive rate of peripheral blood mNGS was significantly higher than that of blood culture and traditional laboratory examination. Peripheral blood mNGS had a high clinical recognition rate, sensitivity, and NPV in the detection of pathogens in patients with hematological diseases accompanied by fever.

[Analysis of COL1A1 gene variation and clinical prevention and treatment in patients with Van der Hoeve syndrome].

Objective: To investigate the clinical phenotype, treatment and prevention of Van der Hoeve syndrome, and analyze the variation characteristics of its related gene COL1A1. Methods: Hearing and sequencing data of syndromic deafness patients who had undergone genetic testing for deafness at the Chinese People's Liberation Army General Hospital since January 2008 to October 2020 were retrospectively reviewed. The variation of the COL1A1 gene and return visits to traceable patients and families were summarized, the disease progress and clinical treatment effects were analyzed, and the prevention strategies were discussed. Results: A total of 7 patients with COL1A1 gene mutation underwent clinical intervention. The mutation sites were c.1342A>T (p.Lys448*), c.124C>T (p.Gln42*), c.249insG(p.Ala84*), c.668insC(p.Gly224*), c.2829+1G>C, c.1081C>T (p.Arg361*), c.1792C>T (p.Arg598*), of which c.1081C>T and c.1792C>T had been previously reported, and the remaining 5 were novo mutations that have not been reported. All the 7 probands underwent stapes implantation and received genetic counseling and prevention guidance. Conclusions: Van der Hoeve syndrome belongs to osteogenesis imperfecta type Ⅰ. The disease has high penetrance. Timely surgical intervention for hearing loss can improve the life quality in patients. Accurate genetic counseling and preimplantation genetic diagnosis can achieve the primary prevention for the disease.

Dendritic cell TLR4 induces Th1-type immune response against Cryptosporidium parvum infection.

The objective of this study was to investigate the mechanism of Toll-like receptor (TLR4)- mediated dendritic cell (DC) immune against Cryptosporidium parvum infection. C. parvum sporozoites were labeled with 5,6-carboxyfluorescein diacetate succinimidyl ester. Murine bone marrow-derived DCs were isolated, and divided into TLR4 antibody blocking (TAB; infected with 2 × 105 labeled sporozoites and 0.5 µg TLR4 blocking antibody), TLR4 antibody unblocking (TAU; infected with 2 × 105 labeled sporozoites), and blank control (BC; with 1.5 mL Roswell Park Memorial Institute 1640 medium) groups. The adhesion of Cryptosporidium sporozoites to DCs and CD11c+ levels were examined by fluorescence microscopy and flow cytometry. Male KM mice were orally injected with C. parvum. The proliferation of T lymphocytes in spleen, expression of cytokines in peripheral blood, and TLR4 distribution features in different organs were further determined by immunohistochemistry. A significantly higher expression of CD11c+ and higher C. parvum sporozoite adhesion were found in the TAU group compared with other groups. The expression of CD4+CD8- /CD8+CD4- in the spleen were obviously differences between the TAB and TAU groups. The expression of TLR4, interleukin IL-4, IL-12, IL-18 and IFN-γ improved in the TAU group compared with TAB group. Higher expression of TLR4 was detected in the lymph nodes of mice in the TAU group, with pathological changes in the small intestine. Hence, TLR4 could mediate DCs to recognize C. parvum, inducing Th1 immune reaction to control C. parvum infection.

Dendritic cell TLR4 induces Th1-type immune response against Cryptosporidium parvum infection

@#The objective of this study was to investigate the mechanism of Toll-like receptor (TLR4)- mediated dendritic cell (DC) immune against Cryptosporidium parvum infection. C. parvum sporozoites were labeled with 5,6-carboxyfluorescein diacetate succinimidyl ester. Murine bone marrow-derived DCs were isolated, and divided into TLR4 antibody blocking (TAB; infected with 2 × 105 labeled sporozoites and 0.5 μg TLR4 blocking antibody), TLR4 antibody unblocking (TAU; infected with 2 × 105 labeled sporozoites), and blank control (BC; with 1.5 mL Roswell Park Memorial Institute 1640 medium) groups. The adhesion of Cryptosporidium sporozoites to DCs and CD11c+ levels were examined by fluorescence microscopy and flow cytometry. Male KM mice were orally injected with C. parvum. The proliferation of T lymphocytes in spleen, expression of cytokines in peripheral blood, and TLR4 distribution features in different organs were further determined by immunohistochemistry. A significantly higher expression of CD11c+ and higher C. parvum sporozoite adhesion were found in the TAU group compared with other groups. The expression of CD4+CD8- /CD8+CD4- in the spleen were obviously differences between the TAB and TAU groups. The expression of TLR4, interleukin IL-4, IL-12, IL-18 and IFN-γ improved in the TAU group compared with TAB group. Higher expression of TLR4 was detected in the lymph nodes of mice in the TAU group, with pathological changes in the small intestine. Hence, TLR4 could mediate DCs to recognize C. parvum, inducing Th1 immune reaction to control C. parvum infection.

Long-chain non-coding RNA LINC01554 promotes NGFR expression and inhibits cell proliferation, migration, and invasion in hepatocellular carcinoma by binding to microRNA-3681-3p.

OBJECTIVE: The aim of this study was to analyze the role of LINC01554 in the pathogenesis of hepatocellular carcinoma (HCC) and explore the potential mechanism through which LINC01554 affects the migration and proliferation of HCC cells. PATIENTS AND METHODS: LINC01554 expression in HCC tissues and its link to the prognosis of patients were analyzed by The Cancer Genome Atlas (TCGA) database. Quantitative Real Time-Polymerase Chain Reaction (qRT-PCR) was carried out to examine LINC01554 levels in 60 cases of HCC clinical tissues and HCC cell lines. Then, LINC01554 overexpression model was constructed using lentivirus in HCC cell lines. HCC proliferation and invasive ability were evaluated through Cell Counting Kit (CCK-8) and transwell tests, respectively. Furthermore, the potential action mechanism of LINC01554 was explored using bioinformatics analysis and in vitro cell experiments. RESULTS: Analysis of the TCGA database revealed that LINC01554 was remarkably under-expressed in HCC tissues. Decreased expression of LINC01554 predicted a poor prognosis for patients. Besides, LINC01554 overexpression markedly blunted the proliferation and migratory capacities of HCC cells. LINC01554 competed with NGFR to bind to microRNA-3681-3p, thereby providing possible mechanisms by which LINC01554 could participate in the progression of HCC. CONCLUSIONS: This study shows for the first time that LINC01554 modulates NGFR expression by binding to microRNA-3681-3p, thereby participating in the progression of HCC.

Pravastatin alleviates oxidative stress and decreases placental trophoblastic cell apoptosis through IL-6/STAT3 signaling pathway in preeclampsia rats.

OBJECTIVE: The aim of this study was to explore the effects of pravastatin on oxidative stress and placental trophoblastic cell apoptosis in preeclampsia rats via the interleukin (IL)-6/signal transducer and activator of transcription 3 (STAT3) signaling pathway. MATERIALS AND METHODS: Experimental rats were randomly assigned into three groups, including control group (C group), model group (M group) and pravastatin group (P group). The rat model of preeclampsia was successfully established. Blood pressure, urinary protein and nitric oxide (NO) as well as oxidative stress indicators in rats were detected at 7, 14 and 21 d, respectively. The content of serum IL-6 was determined via enzyme-linked immunosorbent assay (ELISA). The messenger ribonucleic acid (mRNA) expression of IL-6 in the placenta of rats in each group was detected using quantitative polymerase chain reaction (qPCR). Western blotting (WB) was used to determine the protein expression level of STATs in the placental tissues of rats. In addition, cell counting kit (CCK)-8 assay was conducted to detect the proliferation of rat placental trophoblasts. RESULTS: The content of serum NO was (14.32±2.32) µM in M group, (28.37±3.32) µM in C group and (22.54±3.12) µM in P group, respectively. It was significantly elevated in P group compared with M group (p<0.05). Blood pressure in M group was evidently higher than that in C group at 14 and 21 d (p<0.05). However, P group exhibited distinctly lower blood pressure than M group (p<0.05). No statistically significant differences were observed in the urinary protein of rats among all the three groups at 7 d (p>0.05). At 14 and 21 d, the content of urinary protein in M group was considerably higher than that in C group (p<0.05). However, P group had distinctly lower urinary protein content than M group (p<0.05). Compared with C group, the content of malondialdehyde (MDA) and advanced oxidation protein products (AOPP) rose significantly in M group, whereas the content of superoxide dismutase (SOD) declined remarkably (p<0.05). In comparison with M group, P group exhibited declined MDA and AOPP content and increased SOD content, with statistically significant differences between the two groups (p<0.05). The expression level of serum IL-6 in rats in M group was markedly higher than that in C group (p<0.05). Meanwhile, the expression level of serum IL-6 evidently declined in P group compared with M group (p<0.05). Compared with C group, the protein expressions of phosphorylated STAT1 (p-STAT1) and p-STAT3 were considerably up-regulated in M group (p<0.01). However, they decreased prominently in P group in comparison with M group (p<0.01). C group exhibited a remarkably worse proliferation ability of rat placental trophoblasts than C group (p<0.01). In comparison with M group, the proliferation ability of rat placental trophoblasts was evidently enhanced in P group (p<0.05). Flow cytometry results indicated that the apoptosis of trophoblastic cells increased significantly in M group compared with that in C group (p<0.01). However, it significantly declined in P group in comparison with M group (p<0.05). CONCLUSIONS: Pravastatin can repress the IL-6/STAT3 signaling pathway to alleviate oxidative stress, improve preeclampsia and decrease the apoptosis of placental trophoblastic cells in preeclampsia rats.

[CT manifestations and prognosis of acute paraquat induced lung injury].

Objective: To investigate the CT features of lung injury induced by paraquat poisoning and its relationship with prognosis, and to provide reference for the judgment of the condition and prognosis of paraquat poisoning. Methods: 146 cases of paraquat poisoning patients were treated in the Third People's Hospital of Xuzhou City from January 2013 to April 2016. The cases were divided into mild group, moderate-severe group and fulminant group according to the concentration of paraquat in urine. The clinical data and CT imaging findings were analyzed and reconstructed in three-dimensional reconstruction. The extent of the lesion was observed and the relationship between CT and prognosis was explored. Results: Paraquat lung injury has many manifestations on CT images, and it's performance can be intersecting at the same time. Early lesions lighter cases, late CT imaging lesions can be completely absorbed or residual fibrosis, the prognosis was good; the early lesion was pulmonary consolidation, pleural effusion cases, the late CT image was usually pleural thickening and bronchiectasis, the prognosis was relatively good; early lesions were large patches of ground glass opacity cases, finally, pulmonary fibrosis was common, the mortality rate of 56.57%. There were significant differences in the extent of lung injury between different groups (P<0.001) , and the difference in mortality was statistically significant when the lung injury was different (P<0.001) . Multivariate stepwise Logistic regression analysis showed that ground-glass opacity (OR value=2.013) , interstitial lung fibrosis (OR=3.779) and mediastinal emphysema (OR=33.118) were risk factors for death of lung injury caused by paraquat poisoning (P<0.05) . Conclusion: There were many manifestations on CT images of paraquat lung injury, and the manifestations of paraquat lung injury can be intersecting at the same time. The pulmonary manifestations and outcomes of different paraquat types were different. The CT manifestations of lung injury in paraquat poisoning were mainly exudative changes at early stage, and can be gradually absorbed or evolved into interstitial changes at later stage. The cumulative damage range can be used as a reference for evaluating the prognosis. Ground-glass opacity, interstitial pulmonary fibrosis and mediastinal emphysema are the risk factors for death of lung injury caused by paraquat poisoning.

[Preliminary study of human serum albumin level in early warning onset of preeclampsia].

Objective: To observe the dynamic changes of human serum albumin (HSA) level during pregnancy and study the early warning significance of HSA level on the onset of preeclampsia (PE) . Methods: Totally 369 PE pregnant women (PE group) and 309 normal pregnant women (control group) without PE who admitted in Haidian Maternal and Child Health Hospital from January 2013 to December 2017 were selected. HSA levels were tested before meeting the criterion of PE in the first trimester, the early-third trimester and the late-third trimester, the difference between the two groups were compared. The relationship between the HSA level and the incidence of complications in PE patients was analyzed. Results: (1)The mean values of HSA level in PE group and control group were (41.9±3.1) versus (40.0±2.2) g/L, (34.2±2.7) versus (35.4±2.7) g/L and (33.7±2.9) versus (36.7±3.3) g/L in the first trimester,the early-third trimester and the late-third trimester respectively,the difference in the first trimester was no significance (P>0.05), while the differences in the early-third trimester and the late-third trimester were both significant (all P<0.05). (2) The HSA level during pregnancy of PE group showed a continuous downward trend, while the control group was V-shaped trend. The receiver operating characteristic (ROC) curve analysis showed that PE could be early warned by the decrease of HSA level in PE group [area under curve (AUC)=0.742, cut-off value=5.97 g/L, sensitivity 70.8%, specificity 62.8%], the same result was in severe PE (AUC=0.756, cut-off value=6.85 g/L, sensitivity 70.8%, specificity 72.0%). The level of HSA was negatively correlated with the incidence of complications (r=-0.19, P<0.01). Conclusions: Excessive decrease of HSA level is an early warning factor for PE onset. The higher the baseline of HSA level and the greater the extent of pregnancy decline, the risk of PE in pregnant women is higher. The lower of HSA level in PE, the incidence of complications is higher. The excessive decrease of HSA level may be the first clinical manifestation before the onset of clinical symptoms of PE, so it may be the warning factor and one of the laboratory indicators in the PE sub-clinical stage.