Objective:To evaluate the changes of ventricular function in the twin-to-twin transfusion syndrome (TTTS) fetuses before and after fetoscopy laser photocoagulation (FLP) by fetal heart qualifiction (fetal HQ) technology.Methods:A total of 30 TTTS pregnant women who underwent FLP and delivered in the Third Affiliated Hospital of Zhengzhou University from January 2023 to November 2023 were prospectively selected as the TTTS group, including 30 donor fetuses and 30 recipient fetuses. The control group included 34 normal monochorionic diamniotic (MCDA) twins (68 fetuses) at the same gestational age. The changes of cardiac function of donor and recipient fetuses before and one day, one week and one month after FLP treatment were investigated by fetal HQ. The correlations between stage and global strain(GS) and fractional area change(FAC) of ventricle were analyzed. The inter-observer and intera-observer repeatability tests were performed.Results:①Before FLP treatment, fractional shortening(FS)10-24 of left ventricle and FS10-11 of right ventricle in donor group were lower than the control group (all P<0.05).GS, FAC, FS10-24 of left ventricle and GS, FAC, FS1-24 of right ventricle in recipient group were lower than the control group (all P<0.05). In the donor group, Quintero stage was moderately positively correlated with GS of right ventricle and moderately negatively correlated with FAC of right ventricle ( rs=0.535, -0.515; P=0.004, 0.006). But there were no correlation between Quintero stage and GS and FAC of left and right ventricle in recipient group (all P>0.05). ②After FLP treatment, the left ventricular systolic function of the donor group recovered to the normal level one day after operation ( P>0.05). But the FS16-24 of left ventricle were lower than the control group one week after operation, and the FS21-24 of left ventricle were still lower than the control group one month after operation(all P<0.05). One day after operation, the systolic function of the right ventricle in the donor group decreased, and GS, FAC and FS6-24 of the right ventricle were lower than the control group (all P<0.05). However, the right ventricular systolic function recovered to the normal level one week after operation ( P>0.05). ③After FLP, the systolic function of left ventricle and right ventricle recovered in recipient group, especially for right ventricle. One month after operation, only FS12-16 of left ventricle were lower than the control group ( P<0.05). But GS and FAC of left and right ventricle and 24 segments FS of right ventricle recovered to the control level (all P>0.05). ④The ICC of left and right ventricular parameters were greater than 0.75, indicating good repeatability ( P<0.05). Conclusions:Fetal HQ technology can sensitively evaluate fetal heart function in TTTS fetuses with good repeatability. Before FLP, the ventricular function of donor and recipient fetuses are affected to varying degrees.After FLP, the left and right ventricular function of the donor and recipient fetuses are improved to varying degrees and have different recovery rules.

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.

Abstract Allergic diseases can occur in all systems of the body, covering the whole life cycle, from children to adults and to old age, can be lifelong onset and even fatal in severe cases. Children account for the largest proportion of the victims of allergic disease, Children s allergies start from scratch, ranging from mild to severe, from less to more, from single to multiple systems and systemic performance, so the prevention and treatment of allergic diseases in children is of great importance, which can not only prevent high risk allergic conditions from developing into allergic diseases, but also further block the process of allergy. At present, there is no consensus on the management system of allergic children in kindergartens and primary schools. The "Consensus on Allergy Management and Prevention in Kindergartens and Primary Schools", which includes the organizational structure, system construction and management of allergic children, provides evidence informed recommendations for the long term comprehensive management of allergic children in kindergartens and primary schools, and provides a basis for the establishment of the prevention system for allergic children.

To report a case of Noonan-like syndrome with loose anagen hair, and to detect gene mutations in the family. A 3-year-old female patient presented with a special facial appearance, short stature, deep palmar and plantar creases, and dark skin. The scalp hair was sparse and thin, dermoscopy showed black spot sign, single-hair follicular units, hair shafts varying in the diameter, upright hair and new vellus hair, and constriction of hair shafts and nodular hair were occasionally observed. Peripheral blood samples were collected from the proband and her parents, and the genomic DNA was extracted for whole-exome sequencing. A heterozygous missense mutation c.4A>G was identified in exon 2 of the SHOC2 gene in the proband, resulting in the substitution of serine by glycine at amino acid position 2 (p.S2G) . The mutation was not identified in either of her parents. Combined with the clinical phenotype and gene mutation, the diagnosis of Noonan-like syndrome with loose anagen hair was confirmed.

Objective:To improve the understanding of acute pain after thoracoscopic surgery in patients with early-stage lung adenocarcinoma, to analyze and screen out the independent risk factors that may induce acute postoperative pain. The patients' surgery experience may get improved through the corresponding timely and effective interventions.Methods:We retrospectively reviewed the clinical data of 204 patients with early-stage lung adenocarcinoma who were treated by a single medical team of our center from May 2021 to October 2021, and analyzed the assessment results of acute postoperative pain. Patients were grouped according to the general condition, past medical history, social and spiritual attributes, lesion characteristics, surgical approaches and anesthetic methods. Comparison of proportions of acute postoperative pain between the groups were made, and independent risk factors were identified.Results:A total of 84 males and 120 females were enrolled, with a mean age of(57.9±11.5)years old and a median operation time of 120(110, 145) min. No serious complication or perioperative death occurred in the whole group. Postoperative pain control failed in 76 cases(37.3%), 24 cases(11.8%) suffered from severe postoperative pain, and 33 cases(16.2%) required additional intramuscular injection of strong analgesics after surgery. Those who were younger than 60 years old, with a university degree or above, received two-incision surgery, operated for more than 2 h, received general anesthesia only, or in a state of depression, had significantly higher rates of postoperative acute pain, compared with their respective control groups( P<0.05). The independent risk factors for acute pain after thoracoscopic surgery included age( P=0.002), history of alcoholism( P=0.014), number of incisions( P=0.016), operation time( P=0.010), depression status( P=0.037) and enhanced anesthetic method( P=0.012). Conclusion:A large amount of patients with early-stage lung cancer suffered from acute pain after thoracoscopic surgery, which seriously affected their treatment experience and even quality of life. Young patients with a history of alcoholism and depression status were high-risk groups for postoperative acute pain. Applying Uniportal video-assisted thoracoscopic surgery, reducing the operation time as much as possible, and choosing enhanced analgesic anesthesia represented by epidural block combined with general anesthesia might be effective ways to reduce the probability of acute postoperative pain.

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

Objective:To evaluate the systolic function of 24 segments in dichorionic diamniotic (DCDA) twin pregnancy by fetal heart qualification (fetal HQ) analysis, and to compare the difference with singleton pregnancies.Methods:Thirty-one cases of DCDA twin pregnancy (observation group) and 100 cases of singleton pregnancy (control group) matched in gestational age were enrolled. They underwent perinatal health care in the Third Affiliated Hospital of Zhengzhou University from February 2022 to February 2023.Fetal HQ was applied to track endocardial motion trajectories and automatically calculate the global strain (GS), fractional area change (FAC) and fractional shortening (FS) of 24 segments of left and right ventricles in order to compare the difference between DCDA fetuses and singleton fetuses. One case of twins with growth discordance were selected to demonstrate the utility of this technique.Results:①There were no statistically significant differences in GS, FAC and 24-segments FS of left and right ventricles between the two fetuses in the observation group (all P>0.05). ②The LV-FS of segments 1-10 were higher in the observation group than the control group, and the differences were statistically significant (all P<0.05). However, there were no statistically significant differences in GS and FAC of left and right ventricles, LV-FS of segments 11-24 and RV-FS of segments 1-24 between the observation group and the control group (all P>0.05). The intraclass correlation coefficient(ICC) was greater than 0.75, indicating good repeatability. ③Two fetuses with discordant growth in dichorionic diamniotic twins had abnormal FS in some segments of the left and right ventricles. Conclusions:Fetal HQ technology could easily and reliably evaluate fetal heart function in DCDA pregnancy with good repeatability. The changes of fetal cardiac function in twin pregnancy did not always follow the same pattern as in singleton pregnancy. The related data of singleton pregnancy should not be blindly used in the clinical management and scientific research of twin pregnancy.

Objective To detect the expression of costimulatory molecules B7-H4 and programmed death ligand 1 (PD-L1) in bladder cancer,and to explore the correlation between them and clinicopathological features of bladder cancer.Methods Immunohistochemical staining was used to detect the expression of B7-H4 and PD-L1 in 98 cases of bladder urothelial carcinoma,which were confirmed by pathology from August 2014 to December 2015 in our hospital.There were 23 females,aged 45-82 years,with an average age of 67.8 years.Among them,42 cases of adjacent normal tissues were used as controls.The clinical stage,histological grade and recurrence of bladder cancer were collected,and the correlation between them was analyzed.Results The positive rates of B7-H4 and PD-L1 in bladder urothelial carcinoma were 54.1％ (53/98) and 59.2％ (58/98),respectively,and there was no expression in normal bladder tissues (P ＜ 0.05).The positive expression rate of B7-H4 in muscle invasive bladder cancer (MIBC) patients was higher than that in non-muscle invasive bladder cancer (NMIBC) [73.5％ (25/34) vs.43.8％ (28/64),P =0.005].The positive expression rate of B7-H4 in high-grade patients was higher than that of low-grade [70.0％ (21/30) vs.47.1％ (32/68),P =0.036].The expression rate of B7-H4 in high-risk group was higher than that of low-intermediate risk group [57.1％ (20/35) vs.27.6％ (8/29),P =0.018].The positive expression rate of PD-L1 in patients with MIBC was higher than that in NMIBC [79.4％ (27/34) vs.48.4％ (31/64),P =0.003].The PD-L1 expression rate of histological high-level group was higher than that of low-level group [73.3％ (22/30) vs.52.9％ (36/68)],but the difference was not statistically significant (P =0.058).The PD-L1 expression rate in high-risk group was 68.6％ (24/35),and also higher than low-middle group 24.1％ (7/29) (P ＜ 0.05).There was a positive correlation between the expression of B7-H4 and PD-L1 in bladder urothelial carcinoma (r =0.318,P=0.002).The combined recurrence rate of the two groups was significantly higher than that of the negative expression of the two groups [66.7％ (14/21) vs.30.8％ (8/26),P=0.014].Conclusions The expression of B7-H4 and PD-L1 is up-regulated in bladder urothelial carcinoma,which is closely related to the clinical stage,histological grade,risk classification and recurrence of NMIBC.

Objective To investigate the clinical therapeutic effect of electroacupuncture on ischemic stroke by recording the therapeutic effect score and performing transcranial Doppler (TCD) detection in electroacupuncture-treated convalescent stroke patients before and after treatment.Methods Sixty convalescent patients with ischemic stroke were randomly allocated to treatment and control groups, 30 cases each. The control group received routine medication and the treatment group, electroacupuncture in addition. In the two groups, pre- and post-treatment neurological defect scores were recorded and the clinical therapeutic effects were observed after four weeks of treatment. Pre- and post-treatment middle cerebral artery (MCA) pulsation indices (RI), resistance indices (RI) and ratios of systolic to end-diastolic (S/D) blood flow velocity detected by TCD were compared between the two groups. Results The total efficacy rate was 80.0% in the treatment group and 50.0% in the control group; there was a statistically significant difference between the two groups (P<0.01). There was a statistically significant pre-/post-treatment difference in the MESSS score in the two groups (P<0.01). There was a statistically significant post-treatment difference in the MESSS score between the treatment and control groups (P<0.05). There were statistically significant pre-/post-treatment differences in TCD indices (PI, RI and S/D) on the affected side in the two groups (P<0.05). There were statistically significant post-treatment differences in TCD indices on the affected side between the treatment and control groups (P<0.05).Conclusion Electro- acupuncture can promote rehabilitation in convalescent stroke patients.