Objective:To investigate the effectiveness and safety of the coaxial needle technique in percutaneous liver biopsy for patients with coagulation function abnormalities.Methods:Clinical data of 210 patients who underwent percutaneous liver biopsy using the coaxial needle technique under ultrasound guidance from December 2018 to May 2021 in 3 centers were collected. A retrospective analysis was conducted to compare the puncture success rate, number of samples obtained, pathology qualification rate, intraoperative and postoperative bleeding rates between the group with coagulation function abnormalities and the group with normal coagulation function.Results:After propensity score matching, there were 105 patients in each group, with a puncture success rate of 100% in both groups. The pathology qualification rate was 100% for all samples.Intraoperative bleeding occurred in 78 cases (74.3%, 78/105) in the coagulation function abnormalities group and in 64 cases (61.0%, 64/105) in the normal coagulation function group, with a statistically significant difference between the two groups ( P=0.006). Postoperative bleeding occurred in 3 cases (2.9%, 3/105) in the coagulation function abnormalities group and in 0 case in the normal coagulation function group, with no statistically significant difference between the two groups ( P=0.081). Conclusions:The use of the coaxial needle technique for percutaneous liver biopsy in patients with coagulation function abnormalities not only allows for obtaining an adequate tissue sample but also demonstrates good safety.

Objective:To summarize the ultrasonographic characteristics, genetic etiology, and perinatal prognosis of fetuses with absence of ductus venosus (ADV).Methods:A retrospective study enrolled 84 singleton pregnancies that underwent prenatal ultrasound examination and were diagnosed with fetal ADV at the First Affiliated Hospital of Zhengzhou University from June 2017 to July 2022. Based on prenatal ultrasonographic findings, the cases were divided into isolated ADV group ( n=37), ADV with ultrasound soft markers group ( n=9), and ADV with definite ultrasound abnormalities group ( n=38). According to the gestational age at the initial diagnosis of ADV, they were categorized into early pregnancy group (11-13 weeks of 6 days) with 17 cases, mid-pregnancy group (14-27 weeks of 6 days) with 45 cases, and late pregnancy group (≥28 weeks) with 22 cases. Depending on the direction of blood flow in the intra-abdominal segment of the umbilical vein, they were classified into umbilical vein directly entering the portal sinus group ( n=75), intrahepatic umbilical vein abnormal shunt group ( n=4), and extrahepatic umbilical vein shunt group ( n=5). The clinical characteristics of each group were summarized, and compared using the Chi-square, trend Chi-square tests, Fisher's exact test and Bonferroni correction test. Results:The common ultrasonographic abnormalities in the 84 cases of ADV fetuses were cardiac anomalies (27.4%, 23/84), cystic hygroma (10.7%, 9/84), fetal hydrops (9.5%, 8/84), and body cavity effusion (8.3%, 7/84). The proportions of fetuses with ADV and definite ultrasound abnormalities detected in the early, mid, and late pregnancy were 16/17, 44.4% (20/45), and 9.1% (2/22), respectively, with a higher proportion of definite ultrasound abnormalities associated with earlier detection of ADV ( χ 2trend=27.25, P<0.001). Among them, 21 cases underwent chromosomal karyotyping and/or chromosomal copy number variation sequencing or expanded non-invasive prenatal testing, with five abnormalities detected, including 45,X, trisomy 13, trisomy 22 mosaicism, trisomy 7 mosaicism, and a 14 Mb duplication at 22q12.3q13.33. The neonatal survival (28 days after birth) rates with ADV detected in the early, mid, and late pregnancy gradually increased, at 1/17, 43.9% (18/41), and 90.5% (19/21), respectively ( χ 2trend=27.04, P<0.001). The neonatal survival rates of the isolated ADV group and the group with ultrasound soft markers were higher than that of the group with definite ultrasound abnormalities [93.9% (31/33) and 6/9 vs. 2.7% (1/37), Bonferroni corrected, both P<0.001]. The neonatal survival rates of the umbilical vein directly entering the portal sinus group, intrahepatic umbilical vein abnormal shunt group, and extrahepatic umbilical vein shunt group were 50.0% (35/70), 0/4, and 1/5, respectively, with no statistically significant difference (Fisher's exact test, P=0.105). Conclusions:The earlier the detection of fetal ADV, the more likely it is to be associated with definite ultrasound abnormalities and have lower neonatal survival rates. This highlights the importance of ultrasonographic examination of the fetal ductus venosus. Once ADV is detected, attention should be paid to other potential ultrasound abnormalities, and genetic testing should be completed.

Many epigenetic transcriptome studies have found that N 6 methyladenine (m 6A) methylation, as the most abundant chemical modification on eukaryotic mRNA, plays an important role in the occurrence and development of malignant tumors. It might affect the effectiveness and prognosis of tumor radiotherapy by regulating radiation induced DNA damage, participating in radiation resistance of tumor stem cells, controlling tumor radiosensitivity, intervening in radiation related adverse reactions, and optimizing the synergistic effect of radiotherapy combined with other treatments. In this article, the research progress in the epigenetic mechanism of m 6A RNA methylation modification in tumor radiotherapy was reviewed, aiming to provide ideas for exploring potential new targets for tumor radiotherapy and searching for radiation sensitization and toxicity reduction biomarkers.

One case of COVID-19 infection secondary to pulmonary mucormycosis in a recipient of simultaneous pancreas-kidney transplantation was described. Early identification of the pathogen was achieved by metagenomic next-generation sequencing. On the basis of disease status and liver function changes, targeted treatments included intravenous amphotericin B liposome, amphotericin B nebulization& gargling and subsequently a maintenance therapy of oral posaconazole. This regimen resulted in the absorption of lung infection, stabilization of transplanted pancreas function and reduced levels of creatinine and urea as compared to pre-infection period. The therapeutic efficacy was decent.

Objective:To summarize the distributional characteristics of postoperative occurrence of multi-drug resistant organism (MDRO) infections and their risk factors in simultaneous pancreas-kidney transplantation (SPK) recipients and examine the impact of MDRO infections on the survival of SPK recipients.Method:From January 2016 to December 2022, the relevant clinical data were retrospectively reviewed for 218 SPK recipients. The source of donor-recipient specimens and the composition percentage of MDRO pathogens were examined. According to whether or not MDRO infection occurred post-transplantation, they were assigned into two groups of MDRO (98 cases) and non-MDRO (120 cases). The clinical data of two groups of donors and recipients were analyzed. And the risk factors for an onset of MDRO infection were examined by binary Logistic regression. The survival rate of two recipient groups was compared by Kaplan-Meier method.Result:A total of 98/218 recipients (45%) developed MDRO infections. And 46 (46.9%) of sputum and 34 (34.7%) of urine were cultured positively and 49 (50%) pathogens expressed extended spectrum beta-lactamase. There were pneumonia (46 cases, 46.9%), urinary tract infections (34 cases, 34.7%), abdominal infections (16 cases, 16.3%) and bloodstream infections (2 cases, 2.0%). Univariate regression analysis revealed that length of renal failure ( P=0.037), length of hospitalization ( P<0.001), length of antibiotic use ( P<0.001), novel antibiotics ( P=0.014), albumin ( P<0.001) and leukocyte count ( P<0.001) were risk factors for an onset of MDRO infections. The results of multifactorial regression indicated that low albumin ( OR=0.855, 95% CI: 0.790~0.925, P<0.001) and leukopenia ( OR=0.656, 95% CI: 0.550~0.783, P<0.001) were independent risk factors for an onset of MDRO infections. The survival rates of recipients in MDRO group at Year 1/3 post-operation were 92.9% (91/98) and 89.8% (88/98). And the survival rate of recipients in non-MDRO group was 96.7% (116/120) at Year 1/3 post-operation. Inter-group difference was not statistically significant in 1-year survival rate of two recipient groups ( P=0.201); statistically significant inter-group difference in 3-year survival rate between two recipient groups ( P=0.041) . Conclusion:Low albumin and leukopenia are risk factors for MDRO infection. Infection with MDRO has some impact on the survival of recipients.

Objective Neuromuscular electrical stimulation(NMES)-evoked kinesthetic information in muscle spindle can be purely extracted from the mixed motor and sensory afferents using Ischemic nerve block(INB).This study aims to investigate the somatosensory cortical response evoked by NMES activating muscle spindle afferents in forearm.Methods All subjects performed four experimental tasks designed according to a 2×2 factors,including one factor of the INB state(without INB and within INB)and the other of the stimulation intensity(above and below motor threshold).During the experiment,we recorded EEG data with 64 channels and then beta event-related desynchronization(Beta ERD)were utilized quantize somatosensory cortical excitability evoked by the tasks.The subjective perception about the sensation and movement of the right hand were evaluated by a psychophysical test after the right wrist was performed by INB.Results INB significantly reduced beta ERD on the contralateral somatosensory cortex evoked by NMES above the motor threshold,and there was significant difference of NMES-evoked beta ERD values on the contralateral somatosensory cortex between above and below motor threshold.Meanwhile,contralateral dominance of NMES-evoked beta ERD on the somatosensory cortex was transferred to ipsilateral hemisphere under INB.Conclusion INB can significantly reduce NMES-evoked somatosensory cortical response above motor threshold and decrease cortical perception on the stimulus intensity,which may be due to INB resulting in rapid functional reorganization of somatosensory cortex.

Background::T-cell-mediated immunity is crucial for the effective clearance of viral infection, but the T-cell-mediated immune responses that are induced by booster doses of inactivated severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines in people living with human immunodeficiency virus (PLWH) remain unclear.Methods::Forty-five PLWH who had received antiretroviral therapy (ART) for more than two years and 29 healthy controls (HCs) at Beijing Youan Hospital were enrolled to assess the dynamic changes in T-cell responses between the day before the third vaccine dose (week 0) and 4 or 12 weeks (week 4 or week 12) after receiving the third dose of inactivated SARS-CoV-2 vaccine. Flow cytometry, enzyme-linked immunospot (ELISpot), and multiplex cytokines profiling were used to assess T-cell responses at the three timepoints in this study.Results::The results of the ELISpot and activation-induced marker (AIM) assays showed that SARS-CoV-2-specific T-cell responses were increased in both PLWH and HCs after the third dose of the inactivated SARS-CoV-2 vaccine, and a similar magnitude of immune response was induced against the Omicron (B.1.1.529) variant compared to the wild-type strain. In detail, spike-specific T-cell responses (measured by the ELISpot assay for interferon γ [IFN-γ] release) in both PLWH and HCs significantly increased in week 4, and the spike-specific T-cell responses in HCs were significantly stronger than those in PLWH 4 weeks after the third vaccination. In the AIM assay, spike-specific CD4 + T-cell responses peaked in both PLWH and HCs in week 12. Additionally, significantly higher spike-specific CD8 + T-cell responses were induced in PLWH than in HCs in week 12. In PLWH, the release of the cytokines interleukin-2 (IL-2), tumour necrosis factor-alpha (TNF-α), and IL-22 by peripheral blood mononuclear cells (PBMCs) that were stimulated with spike peptides increased in week 12. In addition, the levels of IL-4 and IL-5 were higher in PLWH than in HCs in week 12. Interestingly, the magnitude of SARS-CoV-2-specific T-cell responses in PLWH was negatively associated with the extent of CD8 + T-cell activation and exhaustion. In addition, positive correlations were observed between the magnitude of spike-specific T-cell responses (determined by measuring IFN-γ release by ELISpot) and the amounts of IL-4, IL-5, IL-2 and IL-17F. Conclusions::Our findings suggested that SARS-CoV-2-specific T-cell responses could be enhanced by the booster dose of inactivated COVID-19 vaccines and further illustrate the importance of additional vaccination for PLWH.

Objective:To explore the involvement of miR-126 and the role of mammalian target of rapamycin (mTOR)/hypoxia-induced factor 1 α (HIF-1 α) pathway in regulating human umbilical cord mesenchymal stem cells (hUCMSCs) exosomes (Exo) on vascular endothelial growth factor (VEGF)-A levels in high glucose-induced human retinal vascular endothelial cells (HRECs).Methods:The hREC was cultured in EGM-2-MV endothelial cell culture medium with 30 mmol/L glucose and placed in hypoxic cell incubator by 1% oxygen concentration. The cell model of high glucose and low oxygen was established. After modeling, divided HRECs into Exo group, phosphate buffer saline (PBS) group, PBS+anti-miR126 group, Exo+anti-miR126 group, PBS+anti-mTOR group, and PBS+anti-HIF-1 α group. High-glucose and hypoxia-induced hREC in the PBS and Exo groups were respectively co-cultured with PBS and 100 μg/ml hUCMSC Exo. PBS+anti-mTOR group, PBS+anti-HIF-1 α group: 500 nmol/L mTOR inhibitor ADZ2014, 25 μmol/L HIF-1 α inhibitor YC-1 pretreatment for hREC 12 h, and then co-culture with PBS after High-glucose and hypoxia-induced. PBS+anti-miR126 group, Exo+anti-miR126 group: miR-126 LNA power inhibitor probe was transfected with high glucose, and co-cultured with PBS and hUCMSC Exo 6 h after transfection. Real-time polymerase chain reaction (qPCR) measured miRNA-126 expression levels in PBS, and Exo groups for 0, 8, 16 and 24 h. After 24 h of co-culture, the levels of mTOR and HIF-1 α in the cells of PBS and Exo groups were detected by immunofluorescence, Western blot and qPCR, respectively. Western blot, qPCR detection of VEGF-A expression levels in cells of the PBS+anti-mTOR and PBS+anti-HIF-1 α groups. The expression of VE GF-A, mTOR, and HIF-1 α mRNA was measured in cells of PBS+anti-miR126 group and Exo+anti-miR126 group by qPCR. Comparison between two groups was performed by t-test; one-way ANOVA was used for comparison between multiple groups. Results:At 0, 8, 16 and 24 h, the relative mRNA expression of miR-126 gradually increased in the Exo group ( F=95.900, P<0.05). Compared with the PBS group, The mTOR, HIF-1 α protein ( t=3.466, 6.804), mRNA in HRECs in the Exo group, VEGF-A mRNA expression ( t=8.642, 7.897, 6.099) were all downregulated, the difference was statistically significant ( P<0.05). The relative expression level of VEGF-A protein ( t=3.337, 7.380) and mRNA ( t=8.515, 10.400) was decreased in HRECs of the anti-mTOR+PBS group and anti-HIF-1 α+PBS group, differences were statistically significant ( P<0.05). The relative expression of VEGF-A, mTOR, and HIF-1 α mRNA was significantly increased in the cells of the Exo+anti-miR126 group, the differences were all statistically significant ( t=4.664, 6.136, 6.247; P<0.05). Conclusions:miR-126 plays a role in regulating the effect of hUCMSCs exosomes on VEGF-A levels in high glucose-induced HRECs via mTOR-HIF-1 α pathway.

BACKGROUND: T-cell immunoreceptor with immunoglobulin and immunoreceptor tyrosine-based inhibition motif domains (TIGIT), an inhibitory receptor expressed on T cells, plays a dysfunctional role in antiviral infection and antitumor activity. However, it is unknown whether TIGIT expression on T cells influences the immunological effects of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) inactivated vaccines. METHODS: Forty-five people living with HIV (PLWH) on antiretroviral therapy (ART) for more than two years and 31 healthy controls (HCs), all received a third dose of a SARS-CoV-2 inactivated vaccine, were enrolled in this study. The amounts, activation, proportion of cell subsets, and magnitude of the SARS-CoV-2-specific immune response of TIGIT + CD4 + and TIGIT + CD8 + T cells were investigated before the third dose but 6 months after the second vaccine dose (0W), 4 weeks (4W) and 12 weeks (12W) after the third dose. RESULTS: Compared to that in HCs, the frequency of TIGIT + CD8 + T cells in the peripheral blood of PLWH increased at 12W after the third dose of the inactivated vaccine, and the immune activation of TIGIT + CD8 + T cells also increased. A decrease in the ratio of both T naïve (T N ) and central memory (T CM ) cells among TIGIT + CD8 + T cells and an increase in the ratio of the effector memory (T EM ) subpopulation were observed at 12W in PLWH. Interestingly, particularly at 12W, a higher proportion of TIGIT + CD8 + T cells expressing CD137 and CD69 simultaneously was observed in HCs than in PLWH based on the activation-induced marker assay. Compared with 0W, SARS-CoV-2-specific TIGIT + CD8 + T-cell responses in PLWH were not enhanced at 12W but were enhanced in HCs. Additionally, at all time points, the SARS-CoV-2-specific responses of TIGIT + CD8 + T cells in PLWH were significantly weaker than those of TIGIT - CD8 + T cells. However, in HCs, the difference in the SARS-CoV-2-specific responses induced between TIGIT + CD8 + T cells and TIGIT - CD8 + T cells was insignificant at 4W and 12W, except at 0W. CONCLUSIONS TIGIT expression on CD8 + T cells may hinder the T-cell immune response to a booster dose of an inactivated SARS-CoV-2 vaccine, suggesting weakened resistance to SARS-CoV-2 infection, especially in PLWH. Furthermore, TIGIT may be used as a potential target to increase the production of SARS-CoV-2-specific CD8 + T cells, thereby enhancing the effectiveness of vaccination.
Humans ; Antibodies, Viral ; CD8-Positive T-Lymphocytes ; COVID-19/complications* ; COVID-19 Vaccines/immunology* ; HIV Infections/complications* ; Receptors, Immunologic ; SARS-CoV-2

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine can induce a potent cellular and humoral immune response to protect against SARS-CoV-2 infection. However, it was unknown whether SARS-CoV-2 vaccination can induce effective natural killer (NK) cell response in people living with human immunodeficiency virus (PLWH) and healthy individuals. METHODS: Forty-seven PLWH and thirty healthy controls (HCs) inoculated with SARS-CoV-2 inactivated vaccine were enrolled from Beijing Youan Hospital in this study. The effect of SARS-CoV-2 vaccine on NK cell frequency, phenotype, and function in PLWH and HCs was evaluated by flow cytometry, and the response of NK cells to SARS-CoV-2 Omicron Spike (SARS-2-OS) protein stimulation was also evaluated. RESULTS: SARS-CoV-2 vaccine inoculation elicited activation and degranulation of NK cells in PLWH, which peaked at 2 weeks and then decreased to a minimum at 12 weeks after the third dose of vaccine. However, in vitro stimulation of the corresponding peripheral blood monocular cells from PLWH with SARS-2-OS protein did not upregulate the expression of the aforementioned markers. Additionally, the frequencies of NK cells expressing the activation markers CD25 and CD69 in PLWH were significantly lower than those in HCs at 0, 4 and 12 weeks, but the percentage of CD16 + NK cells in PLWH was significantly higher than that in HCs at 2, 4 and 12 weeks after the third dose of vaccine. Interestingly, the frequency of CD16 + NK cells was significantly negatively correlated with the proportion of CD107a + NK cells in PLWH at each time point after the third dose. Similarly, this phenomenon was also observed in HCs at 0, 2, and 4 weeks after the third dose. Finally, regardless of whether NK cells were stimulated with SARS-2-OS or not, we did not observe any differences in the expression of NK cell degranulation markers between PLWH and HCs. CONCLUSION s:SARS-CoV-2 vaccine elicited activation and degranulation of NK cells, indicating that the inoculation of SARS-CoV-2 vaccine enhances NK cell immune response.
Humans ; COVID-19 Vaccines/therapeutic use* ; COVID-19 ; SARS-CoV-2 ; Killer Cells, Natural ; HIV Infections ; Antibodies, Viral