[Explorations about the correlation between biological changes of meninges in periodontitis mice and cognitive impairment via single-cell RNA sequencing].

Objective: To clarify the potential correlation between biological changes of meninges in periodontitis mice and cognitive impairment by analyzing the biological changes of meninges in periodontitis mice using single-cell RNA sequencing. Methods: Thirty C57BL/6 mice were divided into two groups by using random number table method (15 mice in each group). Mice in the control group were locally administered 2% carboxyl methyl cellulose (CMC) without Porphyromonas gingivalis (Pg) on both buccal sides. A mixture of Pg and 2% CMC was applied on both buccal sides in the experimental group mice three times a week, lasting for 16 weeks in total. The absorption of alveolar bone, locomotor activity and cognitive function, the activation of microglia and astrocytes in the cortex were observed and assessed. The mRNA expression levels of Occludin in meninges and brain were detected in two groups. Single-cell RNA sequencing data of meninges were processed by uniform manifold approximation and projection (UMAP). Differential genes expressions of endothelial cells were processed by gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. In addition, real-time fluorescence quantitative PCR (RT-qPCR) was used to verify the expressions of Atf3 and Apold1. Results: Methylene blue staining found the distances of buccal and palatal cement-enamel junction-alveolar bone crest (CEJ-ABC) in experimental mice [(185.60±17.60), (206.90±13.37) µm] increased significantly compared with the control group [(135.33±9.57), (163.05±14.98) µm] (t=5.02, P=0.002; t=4.37, P=0.005). Open field experiment showed the total distance and average speed of mice in the experimental group [(971.88±164.57) cm; (3.25±0.55) cm/s] were not statistically significant compared with the control group [(914.24±278.81) cm; (3.05±0.93) cm/s] (t=0.65, P=0.525; t=0.65, P=0.520). The recognition index of the experimental group [(48.02±16.92) %] was lower than the control group [(66.27±17.90) %] (t=2.40, P=0.027) by novel object recognition tests. Compared with the control group [(63.56±11.88) %], the alternation of experimental group [(50.99±14.17) %] was significantly decreased in Y maze tests (t=2.33, P=0.030). Immunohistochemistry results showed microglia and astrocytes were activated in the cortex of experimental mice. Compared with the control group (1.02±0.25, 1.04±0.31), the relative mRNA expressions of Occludin decreased significantly in the meninges and brain of periodontitis mice, respectively (0.61±0.10, 0.64±0.20) (t=3.47, P=0.010; t=2.66, P=0.024). By single-cell RNA sequencing, meninges cells were divided into 11 types, such as endothelial cells, fibroblasts, immune cells and so on. Endothelial cells were the main cell types in meninges [the control group: 26.47% (1 589/6 004), the experimental group: 26.26% (807/3 073)]. Compared with the control group [5.56% (334/6 004)], the percentage of granulocytes increased in the periodontitis mice [11.65% (358/3 073)]. Using clustering analysis to further focus on endothelial cells, GO enrichment analysis revealed differential genes were mainly related to angiogenesis, cell adhesion, apoptosis and so on. KEGG enrichment analysis revealed that differential genes were related to signaling pathways of interleukin-17, relaxin and so on. The relative mRNA expressions of Atf3 and Apold1 in meninges of periodontitis mice (0.42±0.24, 0.54±0.27) were significantly lower than the control group (1.03±0.26, 1.02±0.23) (t=3.88, P=0.005; t=3.02, P=0.017). Conclusions: The mice chronically infected with W83 occurred memory impairment, neuroinflammation and changes of barrier function. In the meninges of periodontitis mice, there were infiltration of immune cells and down-regulation expressions of Atf3 and Apold1 by single-cell RNA sequencing. Meningeal immunity and changes of barrier function may play an important role in the cognitive impairment caused by periodontitis.

[Research progress on pseudocirrhosis].

Presently, pseudocirrhosis occurs in most patients with liver metastases from malignant tumors and can exhibit clinical manifestations related to portal hypertension, such as edema, ascites, and gastrointestinal bleeding. Imaging features include malignant tumor liver metastasis, the appearance of nodules accompanied with or without hepatic contour, segmental liver volume reduction, and caudate lobe enlargement. Histology shows the typical pathological manifestations of liver cirrhosis, such as diffuse tumor cell infiltration, fibrosis around the infiltrating lesion, hepatic sinus vascular thrombosis, nodular hyperplasia, non-accompanied bridging necrosis, bridging fibrosis, and pseudolobule formation. The possible pathogenesis of pseudocirrhosis is tumor cell infiltration and toxic reactions of tumor cells and liver cells to chemotherapy. The presence of pseudocirrhosis in patients diagnosed with malignant tumors is one of the challenges affecting their survival cycle and shortening the median survival time. The relationship between its onset, tumor type and metastasis, and the use of chemotherapy drugs is still unclear. The atypical clinical manifestations and imaging characteristics bring about great challenges for clinicians and patients. Thus, based on the existing case reports, observational studies, and meta-analysis results, this article reviews the research progress on the prevalence, etiology, pathogenesis, diagnosis, treatment, and prognosis of pseudocirrhosis.

[Application of optical coherence tomography in the evaluation of cervical lesions: a multicenter study].

Objective: To explore the value of optical coherence tomography (OCT) imaging system in evaluating cervical lesions in vivo. Methods: A total of 1 214 patients with cervical lesions were collected from January 2020 to December 2021 in the Third Affiliated Hospital of Zhengzhou University, Maternal and Chlid Heaith Hospital of Gushi County, Xinyang City, Henan Province, and Maternal and Chlid Heaith Hospital of Sui County, Shangqiu City, Henan Province. The age of the patients was (38.9±10.5) years (range: 16-77 years). All patients underwent in vivo cervical OCT examination and cervical biopsy pathology examination, and summarized the OCT image features of in vivo cervical lesions. Using the pathological diagnosis as the "gold standard", the accuracy, specificity, sensitivity, positive predictive value (PPV) and negative predictive value (NPV) of OCT image interpretation results were evaluated, as well as the consistency of OCT image diagnosis and pathological diagnosis. At the same time, the in vivo cervical OCT imaging system, as a newly developed screening tool, was compared with the traditional combined screening of human papillomavirus (HPV) and Thinprep cytologic test (TCT), to assess the screening effect. Results: By comparing the OCT images of the cervix in vivo with the corresponding HE images, the OCT image characteristics of the normal cervix and various types of cervical lesions in vivo were summarized. The accuracy, sensitivity, specificity, PPV and NPV of OCT image in the diagnosis of high-grade squamous intraepithelial lesion (HSIL) and above (HSIL+) were 93.4%, 88.5%, 95.0%, 85.0% and 96.2%, respectively. The accuracy, sensitivity, specificity, PPV and NPV of OCT for low-grade squamous intraepithelial lesion (LSIL) were 84.7%, 61.7%, 96.3%, 89.3% and 83.2%, respectively. The consistency between OCT image diagnosis and pathological diagnosis was strong (Kappa value was 0.701).The accuracy, sensitivity and specificity of OCT screening, HPV and TCT combined screening were 83.7% vs 64.9% (χ²=128.82, P<0.001), 77.8% vs 64.5% (χ²=39.01, P<0.001), 91.8% vs 65.4% (χ²=98.12, P<0.001), respectively. The differences were statistically significant. Conclusions: OCT imaging system has high sensitivity and specificity in the evaluation of cervical lesions in vivo, and has the characteristics of non-invasive, real-time and high efficiency. OCT examination is expected to become an effective method for the diagnosis of cervical lesions and cervical cancer screening.

Ratio of 4:1 between ZnGeAs2and MnAs phases in a single composite and its impact on the structure-driven magnetoresistance.

A strong influence of the lattice degree of freedom on magnetoresistance (MR) under high pressure underlies the conception of 'structure-driven' magnetoresistance (SDMR). In most magnetic or topological materials, the suppression of MR with increasing pressure is a general trend, while for some magnetic composites the MR enhances and even shows unusual behavior as a consequence of structural transition. Here we investigated the SDMR in the composite material based on the ZnGeAs2semiconductor matrix and MnAs magnetic inclusions in a phase ratio of 4:1. At ambient pressure, its magnetic and transport properties are governed by MnAs inclusions, i.e. it shows a Curie temperatureTC≈ 320 K and metallic-like conductivity. Under high pressure, the low-field room temperature MR undergoes multiple changes in the pressure range up to 7.2 GPa. The structural transition in the ZnGeAs2matrix has been found at ∼6 GPa, slightly lower than in the pure ZnGeAs2(6.2 GPa). The huge SDMR as high as 85% at 6.8 GPa and 2.5 kOe, which contains both positive and negative MR components, is accompanied by a pressure-induced metallic-like-to-semiconductor-like transition and the enhanced ferromagnetic order of MnAs inclusions. This observation offers a competing mechanism between the robust extrinsic ferromagnetism and high-pressure electronic properties of ZnGeAs2.

An Acid-Responsive Iron-Based Nanocomposite for OSCC Treatment.

Oral squamous cell carcinoma (OSCC) is the most common type of oral cancer, characterized by invasiveness, local lymph node metastasis, and poor prognosis. Traditional treatment and medications have limitations, making the specific inhibition of OSCC growth, invasion, and metastasis a challenge. The tumor microenvironment exhibits mildly acidity and high concentrations of H2O2, and its exploitation for cancer treatment has been widely researched across various cancers, but research in the oral cancer field is relatively limited. In this study, by loading ultra-small Prussian blue nanoparticles (USPBNPs) into mesoporous calcium-silicate nanoparticles (MCSNs), we developed an acid-responsive iron-based nanocomposite, USPBNPs@MCSNs (UPM), for the OSCC treatment. UPM demonstrated excellent dual enzyme activities, generating toxic ·OH in a mildly acidic environment, effectively killing OSCC cells and producing O2 in a neutral environment to alleviate tissue hypoxia. The results showed that UPM could effectively inhibit the proliferation, migration, and invasion of OSCC cells, as well as the growth of mice solid tumors, without obvious systemic toxicity. The mechanisms may involve UPM inducing ferroptosis of OSCC cells by downregulating the xCT/GPX4/glutathione (GSH) axis, characterized by intracellular iron accumulation, reactive oxygen species accumulation, GSH depletion, lipid peroxidation, and abnormal changes in mitochondrial morphology. Therefore, this study provides empirical support for ferroptosis as an emerging therapeutic target for OSCC and offers a valuable insight for future OSCC treatment.

Improving chilling tolerance of peanut seedlings by enhancing antioxidant-modulated ROS scavenging ability, alleviating photosynthetic inhibition, and mobilizing nutrient absorption.

Peanut production is threatened by climate change. Damage to seedlings from low temperatures in early spring can limit yield. Plant adaptations to chilling stress remain unclear in peanut seedlings. It is essential to understand how peanut acquires chilling tolerance. We evaluated effects of chilling stress on growth and recovery of peanut seedlings. We compared and analysed biological characteristics, antioxidants, photosynthesis, biochemical and physiological responses, and nutrient absorption at varying levels of chilling. Compared with chilling-sensitive FH18, the reduced impact of chilling stress on chilling-tolerant NH5 was associated with reduced ROS accumulation, higher ascorbate peroxidase activity and soluble sugar content, lower soluble protein content, and smaller reductions in nutrient content during stress. After removal of chilling stress, FH18 had significant accumulation of O2 •- and H2O2, which decreased photosynthesis, nutrient absorption, and transport. ROS-scavenging reduced damage from chilling stress, allowed remobilization of nutrients, improved chilling tolerance, and restored plant functioning after chilling stress removal. These findings provide a reference for targeted research on peanut seedling tolerance to chilling and lay the foundation for bioinformatics-based research on peanut chilling tolerance mechanisms.

[Construction and validation of an in-hospital mortality risk prediction model for patients receiving VA-ECMO: a retrospective multi-center case-control study].

OBJECTIVE: To investigate the risk factors of in-hospital mortality and establish a risk prediction model for patients receiving venoarterial extracorporeal membrane oxygenation (VA-ECMO). METHODS: We retrospectively collected the data of 302 patients receiving VA-ECMO in ICU of 3 hospitals in Guangdong Province between January, 2015 and January, 2022 using a convenience sampling method. The patients were divided into a derivation cohort (201 cases) and a validation cohort (101 cases). Univariate and multivariate logistic regression analyses were used to analyze the risk factors for in-hospital death of these patients, based on which a risk prediction model was established in the form of a nomogram. The receiver operator characteristic (ROC) curve, calibration curve and clinical decision curve were used to evaluate the discrimination ability, calibration and clinical validity of this model. RESULTS: The in-hospital mortality risk prediction model was established based the risk factors including hypertension (OR=3.694, 95% CI: 1.582-8.621), continuous renal replacement therapy (OR=9.661, 95%CI: 4.103-22.745), elevated Na2 + level (OR=1.048, 95% CI: 1.003-1.095) and increased hemoglobin level (OR=0.987, 95% CI: 0.977-0.998). In the derivation cohort, the area under the ROC curve (AUC) of this model was 0.829 (95% CI: 0.770-0.889), greater than those of the 4 single factors (all AUC < 0.800), APACHE II Score (AUC=0.777, 95% CI: 0.714-0.840) and the SOFA Score (AUC=0.721, 95% CI: 0.647-0.796). The results of internal validation showed that the AUC of the model was 0.774 (95% CI: 0.679-0.869), and the goodness of fit test showed a good fitting of this model (χ2=4.629, P>0.05). CONCLUSION: The risk prediction model for in-hospital mortality of patients on VA-ECMO has good differentiation, calibration and clinical effectiveness and outperforms the commonly used disease severity scoring system, and thus can be used for assessing disease severity and prognostic risk level in critically ill patients.

[Prognostic performance of pulmonary effective arterial elastance in patients with heart failure].

Objective: To explore the predictive value of pulmonary effective arterial elastance (Ea) in patients with heart failure (HF). Methods: This is a retrospective cohort study, which retrospectively included 284 patients with HF who underwent right heart catheterization at Heart Failure Center in Fuwai Hospital between September 2013 and February 2022. Data regarding baseline clinical characteristics, hemodynamic profiles, and prognosis were collected. Ea was calculated as mean pulmonary arterial pressure/stroke volume. Patients were divided into Ea<0.555 group and Ea≥0.555 group according to the median value of Ea (0.555 mmHg/ml, 1 mmHg=0.133 kPa). The primary outcome was the primary clinical event, set as the first occurrence of a series of composite events, including all-cause death, heart transplantation, left ventricular assist device implantation, and HF rehospitalization. Event-free survival was defined as the absence of primary clinical events. Spearman correlation analysis was used to calculate the correlation coefficient between Ea and parameters reflective of right heart function. The Kaplan-Meier analysis was used to compare the different groups for the estimation of outcomes with the log-rank test. We used Cox proportional-hazards regression models to estimate hazard ratios (HR) for primary clinical event. Subgroup analysis was performed based on the age, gender, New York Heart Association (NYHA) functional class, left ventricular ejection fraction, presence of pulmonary hypertension, and serum N-terminal pro-B-type natriuretic peptide (NT-proBNP) values. We used receiver operating characteristic (ROC) curve to calculate the area under the curve (AUC) of Ea for predicting event-free survival in patients with HF. Results: The median age was 51 years, and 206 (72.5%) patients were male. Ea and pulmonary vascular resistance (PVR) were significantly correlated (r=0.698, P<0.001). The correlation between Ea and pulmonary arterial elastance (PAC) were even more significant (r=-0.888, P<0.001). Compared with Ea<0.555 group, Ea≥0.555 group presented with higher serum NT-proBNP values (4 443 (1 792, 8 554) ng/L vs. 1 721 (480, 4 528)ng/L,P<0.001), higher PVR (3.4 (2.5, 4.7) Wood vs. 1.4 (0.9, 2.2) Wood, P<0.001), lower cardiac output (3.0 (2.3, 3.9) L/min vs. 4.3 (3.8, 4.9) L/min, P<0.001), and lower PAC (1.6 (1.3, 2.0) ml/mmHg vs. 4.0 (3.0, 6.0) ml/mmHg, P<0.001). The median follow-up time was 392 (166, 811) days. The Kaplan-Meier survival curve demonstrated a lower event-free survival rate in the Ea≥0.555 group compared to the Ea<0.555 group (Plog-rank<0.001). After multivariate adjustment, Ea (HR=1.734, P<0.001) remained significantly associated with the primary outcome. Subgroup analysis indicated that Ea was associated with the primary outcome across all subgroups. The AUC was 0.724 (P<0.001) for Ea to predict event-free survival calculated from ROC analysis. Conclusions: Ea is closely related to parameters reflective of right ventricular afterload. Increased Ea is an independent predictor of adverse outcomes in patients with HF.

[Metformin suppresses hypoxia-inducible factor-1α expression in cancer-associated fibroblasts to block tumor-stromal cross-talk in breast cancer].

OBJECTIVE: To investigate the mechanism of metformin for regulating tumor-stromal cell cross-talk in breast cancer. METHODS: Tumor associated fibroblasts (CAFs) co-cultured with breast cancer cells were treated with metformin, and the changes in expressions of hypoxia-inducible factor-1α (HIF-1α), p-AMPK, stroma-derived factor-1 (SDF-1) and interleukin-8 (IL-8) in the CAFs were detected using ELISA, RT-qPCR or Western blotting; Transwell assay was used to evaluate the invasiveness of the tumor cells and its changes following treatment with exogenous SDF-1, IL-8 and TGF-ß1. The effects of HIF-1α shRNA or overexpression plasmid, AMPK shRNA, and treatment with OG (a proline hydroxylase inhibitor) or 2-OXO (a proline hydroxylase activator) were examined on p-AMPK, HIF-1α, SDF-1 and IL-8 expressions and invasiveness of the CAFs. RESULTS: Metformin treatment significantly increased the expression levels of p-AMPK, SDF-1 and IL-8 (P<0.05) and decreased HIF-1α expression (P<0.05) without affecting AMPK expression level (P>0.05) in the CAFs. The invasion ability of metformintreated breast cancer cells was significantly decreased (P<0.05). Exogenous SDF-1 and IL-8, HIF-1α overexpression, and OGinduced upregulation of HIF-1α all significantly attenuated the inhibitory effects of metformin on breast cancer cell invasion (P<0.05) and HIF-1α, SDF-1 and IL-8 expressions in CAFs (P<0.05). Transfection with HIF-1α shRNA or treatment with 2-OXO significantly decreased the invasiveness of breast cancer cells (P<0.05). P-AMPK knockdown significantly suppressed the inhibitory effect of metformin on HIF-1α expression in CAFs and on invasion of breast cancer cells (P<0.05). Treatment with TGF-ß1 partially decreased the inhibitory effect of metformin on HIF-1α expression in CAFs and invasiveness of the breast cancer cells (P<0.05). CONCLUSION: Metformin suppresses HIF-1α expression in CAFs to block tumor-stromal cross talk in breast cancer.

[Gastrointestinal tumors with SWI/SNF complex deficiency: a clinicopathological analysis of 36 cases].

Objective: To investigate the clinicopathological characteristics of gastrointestinal tumors with SWI/SNF complex deficiency and to perform a prognostic analysis of the patients. Methods: Gastrointestinal tumor cases with SWI/SNF complex deficiency expression diagnosed at the Department of Pathology, Zhongshan Hospital, Fudan University, Shanghai, China from August 2021 to May 2023 were collected. Hematoxylin and eosin (HE) stained slides were reviewed, and immunohistochemical results were analyzed. Clinical and pathological information was recorded, and relevant literature was reviewed. Results: A total of 36 cases of gastrointestinal tumor with loss of SWI/SNF complex expression were identified, including 28 males (77.8%) and 8 females (22.2%). The average age at diagnosis was 70 years (range 48-85 years). Clinical staging showed 3 cases in stage Ⅰ (8.3%), 12 cases in stage Ⅱ (33.3%), 19 cases in stage Ⅲ (52.8%), and 2 cases in stage Ⅳ (5.6%). Complete or partial loss of ARID1A expression was observed in 20 cases (55.6%); complete or partial loss of SMARCA2 expression was observed in 24 cases (66.7%). SMARCA4 exhibited complete loss of expression in 4 cases (11.1%). Eleven cases (30.6%) showed concurrent complete or partial losses of both ARID1A and SMARCA2 expression. Twelve cases (33.3%) had mismatch repair protein deficiency, all of which were characterized by MLH1/PMS2 absence. Mismatch repair protein deficiency was associated with loss of ARID1A expression (P<0.01). Patients with mismatch repair protein deficiency were also associated with earlier clinical stage and a lower risk of lymph node metastasis compared to the ones with intact mismatch repair proteins (P<0.05). Conclusions: SWI/SNF complex deficiency in gastrointestinal tumors is associated with dedifferentiation and often accompanied by mismatch repair protein deficiency. Compared to the cases with intact mismatch repair proteins, the cases with defective mismatch repair protein have an earlier clinical stage and a lower risk of lymph node metastasis.

[Mid-term analysis of prospective cohort study of rivaroxaban in preventing CRT in breast cancer].

Objective: To explore the efficacy and safety of Rivaroxaban in preventing catheter related thrombosis (CRT) in patients with breast cancer who are undergoing central venous catheter chemotherapy, and provide basis for making standardized prevention and treatment strategies. Methods: In this research, a prospective cohort study was adopted, and breast cancer patients who received central venous catheter chemotherapy in Sanhuan Cancer Hospital during September 2020 to March 2022 were selected as a treatment group to take the rivaroxaban anticoagulation therapy with 10 mg.po.qd for one month. The control group got no preventive anticoagulation therapy. Vascular ultrasound examination was taken to confirm the occurrence of CRT, and a chi-square test was done for comparison the disparity between the groups. Logistic regression was applied to analyze the univariate and multivariate factors for the formation of CRT. Results: In the research, a total of 235 patients were selected, and there were a total of 19 035 days of catheterization with 81 days of catheterization on average. While in the control group, the incidence of CRT was 28.0% (33/118), the incidence of CRT in the treatment group was 20.5% (24/117), the difference was no significant (P=0.183). Subgroup analysis results showed that the peripherally inserted central catheter (PICC) was performed in 165 cases with the CRT incidence of 18.2% (30/165) and thrombosis was mostly seen around axillary vein, accounting for 63.3%. Subclavian vein catheterization was performed in 63 cases with the CRT incidence of 39.7% (25/63), and thrombosis was mostly seen around subclavian vein, accounting for 88.0% (22/25). Implantable venous access port was implanted in 7 cases around subclavian vein and internal jugular vein with the CRT incidence of 28.6% (2/7). The patients who developed CRT within 30 days after catheterization accounted for 54.4% (31/57), 22.8% (13/57) in a period during 30 days and 60 days) and 22.8% (13/57) in a period during 60 days and 180 days). The diagnosed CRT patients had been treated with rivaroxaban 15 mg.bid.po for 3 months. During the 3 months, 100.0% of the thrombosis waned, 71.9% (41/57) of the thrombosis waned within 30 days, 19.3% (11/57) in a period during 30 and 60days and 8.8% (5/57) in a period during 60 days and 90 days. Univariate and multivariate analysis indicated that the risk of CRT in subclavian vein catheterization was higher than that in PICC, respectively (OR=2.898, 95% CI:1.386-6.056 P=0.005), and the type of catheterization was an independent factor for the formation of thrombosis. Safety analysis result showed that in the prevention of CRT, rivaroxaban treatment did not induce drug-related bleeding, liver function damage, bone marrow suppression or any other side effects. While CRT diagnosed patients were treated with anticoagulation, they kept the central venous catheter, and the infusion was smooth. These patients all finished the anti-tumor treatment as planned, and no abnormalities like new thrombosis or pulmonary embolism were observed. Conclusions: In the mid-term analysis, the proportion of Rivaroxaban in preventing anticoagulant CRT decreases, but it don't reach statistical significance. The sample size should be further increased for observation. Rivaroxaban is proved effective and very safe in the treatment of CRT, and does not affect the concurrent chemotherapy. Medical personnel should carry out the policy of "early prevention, early detection and early treatment" for CRT so as to improve the patients' quality of life.

[Effect of sirolimus combined with anti-CD20 monoclonal antibody desensitization on the prognosis of patients underwent haploidentical stem cell transplantation].

Objective: To investigate the effects of sirolimus combined with anti-CD20 monoclonal antibody desensitization on the prognosis of patients with haploidentical stem cell transplantation (haplo-SCT). Methods: Fifteen consecutive patients who received haplo-SCT and pre-transplant donor specific anti-human leukocyte antigen (HLA) antibody (DSA) positive [mean fluorescence intensity (MFI)≥2 000] in the Institute of Hematological Diseases from November 2021 to March 2023 were retrospectively recruited into the desensitized group. There were 4 males and 11 females, with a median age [M(Q1, Q3)] of 48 (37, 59) years. All patients were desensitized with sirolimus combined with anti-CD20 monoclonal antibody. The non-desensitized group included 29 patients with haplo-SCT who had not received desensitization treatment from August 2012 to June 2016. There were 12 males and 17 females with a median age of 42 (26, 50) years. Up to October 1, 2023, the median follow-up time was 13 (9, 18) months in the study group and 23 (14, 29) months in the control group. The changes of MFI before and after desensitization treatment and the prognosis of patients in the desensitized group were compared, including the incidence of primary implantation failure (pGF), neutrophil implantation time, platelet implantation time, grade Ⅱ-Ⅳ acute graft-versus-host disease (GVHD) and chronic GVHD incidence, non-recurrence related mortality, event-free survival rate, disease-free survival rate and overall survival rate. The survival curve was drawn by Kaplan-Meier method, and the survival rate between groups was compared with Log-rank test. Results: After desensitization treatment, the level of DSA MFI in the desensitized group decreased from 8 879 (7 544, 11 495) to 3 781 (1 638, 4 165) after desensitization treatment (P<0.01). All of the patients achieved hematopoietic recovery, and the median time for neutrophil and platelet engraftment were 14 (11, 15) and 20 (18, 25) days, respectively. The incidence of pGF in the desensitized group was 0, which was lower than that in the non-desensitized group (34.5%, 10/29) (P=0.011). The expected 1-year disease-free survival rate and overall survival rate in the desensitized group were 100% (15/15) and 100% (15/15) respectively, while those in the non-desensitized group were 75.9% (22/29) and 75.9% (22/29) respectively, the difference was not statistically significant (both P>0.05). The one-year event-free survival rate in the desensitized group was expected to be 100% (15/15), which was higher than that in the non-desensitized group (51.3%, 15/29) (P=0.002). Conclusion: Sirolimus combined with anti-CD20 monoclonal antibody desensitization therapy can reduce the DSA level of haplo-SCT recipients, promote hematopoietic engraftment after transplantation, and avoid the occurrence of pGF after transplantation.

[Characteristics of baseline viral load before antiretroviral therapy in newly reported HIV-infected patients in Tianjin, 2019-2022].

Objective: To understand the baseline viral load (VL) of newly reported HIV- infected patients before antiretroviral therapy and related factors in Tianjin. Methods: Data were obtained from the China Disease Control and Prevention Information System, and the study subjects were HIV-infected patients before the first antiretroviral therapy in Tianjin from 2019 to 2022, and the information about their socio-demographic characteristics, baseline CD4+T lymphocyte (CD4) counts before antiretroviral therapy and baseline VL test results were collected, the baseline high VL was defined as ≥100 000 copies/ml. The effect of different factors on viral load were analyzed. Software SPSS 24.0 was used for statistical analysis. Results: A total of 1 296 newly reported HIV-infected patients were included in the study, in whom 15.89% (206/1 296) had high baseline VL, and multifactorial logistic regression analysis showed that those with history of STD (aOR=1.45, 95%CI:1.00-2.08) were more likely to have high baseline VL. Compared with those with baseline CD4 counts <200 cells/µl, those with baseline CD4 counts 200-350 cells/µl (aOR=0.40, 95%CI: 0.27-0.57), 351-500 cells/µl (aOR=0.32, 95%CI: 0.20-0.49), and >500 cells/µl (aOR=0.30, 95%CI: 0.18-0.49) were less likely to have high baseline VL. Conclusions: The proportion of HIV-infected patients with high baseline VL before antiretroviral therapy was low in Tianjin during 2019-2022. History of STD and baseline CD4 counts <200 cells/µl were associated with high baseline VL in HIV-infected patients, to which close attention needs to be paid in AIDS prevention and control.

[Research progress on neurotoxicity induced by metal pollutants through astrocytes].

Metal pollutants in the natural environment and industrial environment can enter organisms through the respiratory tract and digestive tract causing adverse health effects. Many kinds of literatures confirm that metal pollutants have neurotoxicity. Recent studies have showed that astrocytes play an important role in neurotoxicity induced by metal pollutants. In this review, the latest progress of neurotoxicity induced by lead, mercury, cadmium, antimony and copper through astrocytes in recent years is summarized, which provides a new clue for the neurotoxicity research of metal pollutants.

[System analysis of the ecological distribution of bacteriophages in hospital wastewater].

Phage therapy is one of the most important tools for the treatment of infections with multi-drug resistant bacteria. Such phages are usually isolated from hospital effluents, however, no systematic study on the distribution of phages in hospital effluents has been conducted so far. The aim of this study was to isolate the corresponding phages of common pathogenic bacteria isolated in the clinic as hosts, so as to assess the ecological distribution of phages in hospital wastewater and to provide a reference for the isolation and application of phages of drug-resistant bacteria in the clinic. A cross-sectional study design was used in this study. The 125 pathogenic bacteria (belonging to 16 different strains) isolated from the clinical microbiology laboratory of Qilu Hospital of Shandong University from May to June 2023 were selected as the target strains, and the phages corresponding to these strains were isolated and purified from the hospital wastewater by using the double-layer plate sandwich method. At the same time, the distribution of pathogenic bacteria in the same batch of wastewater was analyzed with the help of mNGS sequencing technology, so as to preliminarily investigate the abundance correspondence between pathogenic bacteria and phages in wastewater. The results showed that a total of 56 phage strains were isolated from 125 clinical pathogens as hosts, corresponding to six pathogens, including Acinetobacter baumannii, Klebsiella pneumoniae, Escherichia coli, Staphylococcus aureus, Pseudomonas aeruginosa, and Stenotrophomonas maltophilia. All six pathogenic bacteria contained strains with different degrees of drug resistance, with a higher percentage of multi-drug resistant strains in A. baumannii, Escherichia coli and P. aeruginosa. The phage acquisition rates of these six pathogens were, in descending order, Escherichia coli (80%), Stenotrophomonas maltophilia (75%), Pseudomonas aeruginosa (70%), Klebsiella pneumoniae (66.67%), Acinetobacter baumannii (36.36%) and Staphylococcus aureus (12.5%). Preliminary mNGS sequencing results showed that the pathogenic bacteria with higher abundance in the batch of effluent were Enterococcus faecalis, Klebsiella pneumoniae, Escherichia coli, Enterococcus faecalis, Acinetobacter baumannii, Klebsiella aerogenes, Klebsiella michiganensis and Pseudomonas aeruginosa. In conclusion, phages of most common clinical Gram-negative pathogens were isolated from hospital wastewater with high isolation rates; however, phages of Gram-positive pathogens were isolated at lower rates, and only phages corresponding to Staphylococcus aureus were isolated in this study. The corresponding mNGS sequencing results showed that the distribution of Gram-negative pathogens in sewage may had a positive correlation with the ecological distribution of phages.

[Oncological outcomes of laparoscopic radical trachelectomy for early stage cervical cancer].

Objective: To analyze and summarize the oncological outcomes after laparoscopic radical trachelectomy (LRT) for early stage cervical cancer. Methods: The clinical data and follow-up results of 148 patients with early stage cervical cancer who underwent LRT in Renji Hospital, School of Medicine, Shanghai Jiao Tong University from July 2014 to June 2023 were collected, while tumor outcomes and postoperative pregnancy were analyzed retrospectively. Results: (1) General situation: the median age of 148 patients with LRT was 33 years (range: 19-42 years). Pathological type: 111 cases of squamous cell carcinoma, 36 cases of adenocarcinoma, 1 case of adenosquamous carcinoma. International Federation of Gynecology and Obstetrics (2018) stage: 17 cases of stage Ⅰa1 with lympho-vascular space invasion, 25 cases of stage Ⅰa2, 102 cases of stage Ⅰb1, and 4 cases of stage Ⅰb2. (2) Tumor outcomes: 148 patients were followed up regularly after LRT, and the median follow-up time was 59 months (range: 2-104 months). During the follow-up period, 5 cases of tumor recurred (including 1 death), and the median recurrence time was 10 months (range: 4-33 months). Among them, there were 3 cases of pelvic metastasis, 1 case of distant metastasis, and 1 case of both pelvic and distant metastasis. Both 3-year and 5-year disease-free survival rates of 148 patients were 94.5%, and the 5-year overall survival rate was 98.9%. (3) Postoperative pregnancy: among 148 patients with LRT, 67 patients had pregnancy requirements, followed up for 1 year, and 20 of them were pregnant, with a pregnancy rate of 29.9% (20/67). Among the 20 pregnant patients, 2 cases early abortion, 1 case mid-term abortion, and 17 cases gave birth (including 4 cases of premature birth and 13 cases of full-term birth). Conclusion: Under the condition of strict control of surgical indications, guaranteed surgical scope and tumor-free operation, LRT in patients with early cervical cancer has a good outcome.

Knowledge domain and emerging trends in sacubitril/valsartan study from 2008 to 2023 - a visualized conclusive analysis based on novel scientometric tools.

OBJECTIVE: This study aimed to determine the evolution of sacubitril-valsartan research and analyze the publications quantitatively and qualitatively. MATERIALS AND METHODS: We used the bibliometric method and a combination of CiteSpace_6.1.6 and VOSviewer_1.6.18 to identify top authors, countries, institutions, co-cited articles, co-cited journals, keywords, and trends. This study prioritized key aspects in the existing global research on Entresto (Sacubitril/Valsartan) to assess our depth of knowledge in this field and identify potential insights. The objective was to generate a reference for the utilization of the "angiotensin receptor-neprilysin inhibitor" (ARNI). RESULTS: From 2008 to 2022, citations of sacubitril-valsartan showed an upward trend. VOSviewer keyword analysis of 3,408 publications identified 624 keywords and divided them into seven different clusters. The clustered network was constructed based on 1,191 references cited by 3,408 publications that met the terms, where the clustered network of sacubitril-valsartan was presented. These publications can be regarded as fundamental to Entresto's research. Analysis of co-cited reference clusters showed that other than Entresto's novel application in other diseases, the new combination with other medication or mechanical assistance therapies against heart failure was Entresto's latest focus. Analysis of citation bursts showed that the rank of the top 25 keywords, according to the chronological sequence, marked Entresto's research entering a new era of exploring the extended application in other diseases and novel combinations with other diverse therapies. CONCLUSIONS: We found that emerging new mechanisms in sacubitril-valsartan therapy intended for more targets in the pathogenesis of specific diseases will be the focus of further studies.