Mechanical ventilation has, since its introduction into clinical practice, undergone a major evolution from controlled ventilation to diverse modes of assisted ventilation. Conventional mechanical ventilators depend on flow sensors and pneumatic pressure and controllers to complete the respiratory cycle. Neurally adjusted ventilatory assist (NAVA) is a new form of assisted ventilation in recent years, which monitors the electrical activity of the diaphragm (EAdi) to provide an appropriately level of pressure support. And EAdi is the best available signal to sense central respiratory drive and trigger ventilatory assist. Unlike other ventilation modes, NAVA breathing instructions come from the center. Therefore, NAVA have the synchronous nature of the breaths and the patient-adjusted nature of the support. Compared with traditional ventilation mode, NAVA can efficiently unload respiratory muscles, relieve the risk of ventilator-induced lung injury (VILI), improve patient-ventilator coordination, enhance gas exchange, increase the success rate of weaning, etc. This article reviews the research progress of NAVA in order to provide theoretical guidance for clinical applications.
Humans ; Interactive Ventilatory Support ; Respiration, Artificial ; Positive-Pressure Respiration ; Diaphragm/physiology* ; Respiratory Muscles/physiology*

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

Background Hand-arm vibration disease (HAVD) is a chronic progressive disease caused by long-term exposure to hand-transmitted vibration, but the mechanism by which vibration affects peripheral vascular function of fingers is not completely clear. Objective To study the association between vasoactive factors and HAVD, and to screen specific indicators for its early diagnosis and prevention. Methods Judgmental sampling method was used to select workers with (HAVD group) and without HAVD (vibration contact group), and non-hand-transmitted vibration operation workers (control group), with 60 workers in each group. The levels of leukotriene B4 (LTB4), vascular endothelial growth factor (VEGF), 5-hydroxy tryptamine (5-HT), interleukin-1β (IL-1β), and calcitonin gene-related peptide (CGRP) in plasma of the three groups were measured by enzyme-linked immunosorbent assay. The association between vasoactive factors and HAVD was analyzed using logistic regression, and the diagnostic HAVD indicators were screened by receiver operator characteristic (ROC) curve of a multivariate model indicator \begin{document}$ \widehat{Y} $\end{document}. Results The hand symptom rates of the HAVD group, the vibration contact group, and the control group were 26.7%, 66.7%, and 96.7% respectively, with a significant difference (P<0.05). The levels of LTB4, 5-HT, IL-1β, and CGRP in the HAVD group were the highest followed by the vibration contact group, and lowest levels were in the control group (P<0.05). There was no significant difference in the VEGF level among the three groups (P>0.05). The logistic regression results showed that higher levels of LTB4 (OR=1.048, 95%CI: 1.022-1.076), 5-HT (OR=1.011, 95%CI: 1.004-1.018), IL-1β (OR=1.148, 95%CI: 1.071-1.230), and CGRP (OR=1.055, 95%CI: 1.008-1.104) were associated with a higher risk of HAVD (P<0.05). The order of the potential indicators' area under the ROC curve from high to low was:\begin{document}$ \widehat{Y} $\end{document} (0.969) > IL-1β (0.907) > LTB4 (0.876) > 5-HT (0.858) > CGRP (0.836). Conclusion The expression levels of LTB4, 5-HT, IL-1β, and CGRP are altered with occupational exposure in hand-transmitted vibration operations and may be associated with HAVD; VEGF is not found to be associated with HAVD. The accuracy of early screening for HAVD can be improved by combining the monitoring of various biochemical indicators.

Background Prolonged exposure to vibration can cause vascular endothelial injury, and inflammatory response plays an important role in vascular endothelial injury. Studies have shown that long non-coding RNA (lncRNA) maternally expressed gene 3 (MEG3) is involved in regulating the expression of inflammatory injury of endothelial cells. Objective To investigate the effects of vibration on the secretion of inflammatory factors and the expression of IncRNA MEG3 by vascular endothelial cells in vitro. Methods Human umbilical vein endothelial cells (HUVEC) were divided into two categories: vibration and control. The vibration exposure included 63 Hz (6.76 m·s⁻²), 200 Hz (5.08 m·s⁻²), and 250 Hz (4.56 m·s⁻²) frequency bands, and 1 and 2 d exposure time with 1 to 4 h of daily vibration. The control treatment was the same as the vibration category except that they were not exposed to vibration. CCK-8 was used to detect the effects of different vibration frequencies and time on the viability of HUVEC. The expression levels of tumor necrosis factor-α (TNF-α), interleukin-8 (IL-8), interleukin-4 (IL-4), and interleukin-10 (IL-10) in the cells and supernatants were detected by enzyme-linked immunosorbent assay. The expression levels of IncRNA MEG3 were detected by real-time fluorescence quantitative PCR. Results Compared with the cells with the control treatment, the cell viability of the 1-day exposure group increased after 1.5 h and 3 h of vibration at 63 Hz, while decreased after 2 h and 2.5 h; the cell viability of the 2-day exposure group increased at the frequency of 63 Hz for 1.5 h, but decreased at 2 h and 2.5 h. At the frequency of 200 Hz, the cell viability of the 1-day exposure group increased at 2 h and 4 h, but decreased at 2.5 h and 3 h; the cell viability of the 2-day exposure group increased at 1.5 h and decreased at 2.5 h. For the vibration exposure at frequency of 250 Hz, the cell viability of the 1-day exposure group increased at 1.5 h and 2.5 h, but decreased at 3 h; of the 2-day exposure group, the cell viability increased at 1.5 h and decreased at 3 h. For the exposure settings of 63 and 200 Hz vibration for 2.5 h and 250 Hz vibration for 3 h, and with the control treatment as reference, the expression levels of TNF-α, IL-8, IL-4, and IL-10 in cells and supernatants were increased in the 1 d and 2 d exposures; the expression level of lncRNA MEG3 decreased in the 1 d exposure group; however, for the 2 d exposure, the expression level of lncRNA MEG3 decreased only in the 63 Hz vibration exposure. All of these results were statistically significant (P<0.05). Conclusion Vibration could induce an increase in the levels of inflammatory factors TNF-α, IL-8, IL-4, and IL-10 and a decrease in the expression level of lncRNA MEG3 in vascular endothelial cells in vitro.

Background Long-term exposure to hand-transmitted vibration can lead to hand-arm vibration syndrome, one manifestation of which is impaired peripheral blood circulation in the arms. Altered expressions of prostacyclin I₂ (PGI₂) and thromboxane A₂ (TXA₂) in blood may be one of the important mechanisms of vibration-induced hand-arm vibration syndrome. Objective To reveal the effects of rat tail vibration on the expressions of PGI₂ and TXA₂ in plasma, and to establish the correlation between the change of rat plasma PGI₂ to TXA₂ ratio and rat tail vibration. Methods Fifty SPF-grade male SD rats were randomly divided into five groups: control group, 1 d exposure group, 3 d exposure group, 7 d exposure group, and 14 d exposure group, with 10 rats in each group. The rats were placed in rat immobilizes on a immobilization table, and the rats' tails were connected to a shaker and fixed with medical tape. There was no overlap between the immobilizes and between the rats' tails by no contact between the immobilization table and the shaker. The exposure dose was 125 Hz, 5.9 m·s⁻², 4 h·d⁻¹, and the vibration direction was linear vertical vibration. Abdominal aortic blood was taken at the end of vibration exposure, and the expressions of PGI₂, TXA₂, and their hydrolysates 6-keto-prostaglandin F_1α (6-keto-PGF_1α) and thromboxane B₂ (TXB₂) were measured by enzyme-linked immunosorbent assay, and the 6-keto-PGF_1α/TXB₂ values were calculated. Spearman rank correlation was used to analyze whether the expression of vascular factors correlated with the accumulated time of vibration. Results The expression levels of plasma 6-keto-PGF_1α were (896.12±124.37), (1068.13±119.41), (1215.26±122.64), and (1317.94±106.54) ng·L⁻¹ in the 1 d, 3 d, 7 d, and 14 d groups of rats, respectively, which were higher than that in the control group, (830.60±109.47) ng·L⁻¹ (P<0.001). The PGI₂ expression levels were (86.49±2.40), (107.90±2.65), (114.02±2.16), and (126.95±1.94) ng·L⁻¹ in the 1 d, 3 d, 7 d, and 14 d groups of rats, respectively, all higher than (60.09±2.11) ng·L⁻¹ in the control group (P＜0.001). The expression levels of TXB₂ were (132.14±4.10), (145.52±4.09), (179.91±4.98), and (204.10±3.22) ng·L⁻¹ in the 1 d, 3 d, 7 d, and 14 d groups of rats, respectively, which were higher than that in the control group, (106.08±3.26) ng·L⁻¹ (P<0.001). The expression levels of plasma TXA₂ were (211.99±3.24), (236.33±3.88), and (245.45±4.23) ng·L⁻¹ in rats in the 3 d, 7 d, and 14 d groups, respectively, which were all elevated compared with (174.79±4.19) ng·L⁻¹ in the control group (P<0.001). Compared with the control group, the 6-keto-PGF_1α/TXB₂ values were decreased in the 7 d and 14 d groups (P<0.05). The 6-keto-PGF_1α, PGI₂, TXB₂, and TXA₂ expressions were positively correlated with vibration accumulation time (r=0.84, 0.84, 0.80, 0.84, P<0.001) and the 6-keto-PGF_1α/TXB₂ values were negatively correlated with vibration accumulation time (r=-0.24, P=0.003). Conclusion Local exposure of rat tail to vibration could increase the expressions of PGI₂ and TXA₂ in blood, and the elevated expressions show a dose-effect relationship with the duration of vibration exposure, but the PGI₂/TXA₂ tends to decrease with the accumulation of vibration exposure.

Background The metabolites and metabolic pathways of hand-arm vibration syndrome have not yet been elucidated. Objective To investigate the effect of local vibration on endogenous metabolites in rat serum by metabolomic analysis, to preliminarily explore the potential metabolic pathway of endogenous metabolites, so as to provide evidence for further research on the mechanism of hand-arm vibration syndrome. Methods Thirty-two SPF male SD rats, (211.3±11.1) g, 7−8 weeks of age, were selected and randomly divided into three groups: control group (14 rats, without vibration), 7 d vibration group (9 rats, continuously vibration for 7 d), and 14 d vibration group (9 rats, continuous vibration for 14 d). The vibration rats were vibrated every day for 4 h, the frequency weighted acceleration was 4.9 m·s⁻², the vibration frequency was 125 Hz, and the vibration direction was one-way vertical vibration. The control group had the same conditions except not contacting vibration. After the vibration exposure, the blood samples taken from the abnormal aorta of rats were collected, and the changes of rat serum metabolome were analyzed by ultra-performance liquid chromatography-tandem time-of-flight mass spectrometry. Principal components analysis (PCA) was used to explore changes in rat serum metabolic profile, and orthogonal partial least squares-discriminant analysis (OPLS-DA) was used to screen out differential metabolites. Combined with online databases, a metabolic pathway enrichment analysis of differential metabolites was performed. Results The PCA analysis showed that compared with the control group, the rat serum metabolic profiles in the 7 d group and the 14 d group were clearly differentiated, and the rat serum metabolic profiles in the 7 d group and the 14 d group partially overlapped. The OPLS-DA analysis showed significant differences between groups. The main parameters were: model interpretation rate R²Y=0.914, model predictive ability Q²=0.58. The OPLS-DA analysis screened out 26 and 119 differential metabolites from the 7 d group and the 14 d group respectively, and there were 24 common differential metabolites between the 7 d group and the 14 d group. The metabolomic pathway analysis showed that local vibration-induced changes in rat serum metabolism were mainly related to arachidonic acid metabolism in the 14 d group, among which the metabolites with significant effects were arachidonic acid, prostaglandin E₂, and prostaglandin D₂. Conclusion Local vibration could affect the normal metabolism in rats, and the metabolic pathway with significant influence is arachidonic acid metabolism after a 14 d exposure and the involved metabolites are arachidonic acid, prostaglandin E₂, and prostaglandin D₂.

Objective:To summarize the clinical and genetic characteristics of Potocki-Shaffer syndrome (PSS).Methods:A retrospective study was conducted to analyze the clinical data of 1 patient diagnosed with PSS in the Department of Pediatrics of the Sixth Affiliated Hospital, Sun Yat-Sen University at February 2021.The data analyzed included clinical manifestations, biochemical tests and gene tests.Meanwhile, studies were retrieved from the China National Knowledge Internet database, Wanfang database, and PubMed database from the establishment of the database to December 2021 by taking " Potocki-Shaffer syndrome" " EXT2 gene" " AlX4 gene" and " PHF21A gene" as key words.Besides, genes were searched from the Online Frontal Analysis Mendelian Inheritance in Man.The clinical and genetic features of PSS patients were summarized. Results:The patient was 5 months and 21 days old, male, who was admitted to the hospital due to excessive growth in body mass for the past 3 months.The patient showed mental and motor retardation, overgrowth, concealed penis, hearing loss, and hypotonia.Whole exon sequencing of this patient revealed heterozygous deletions in the Chr11: 44069455-48188946 region, including the deletions of 3 autosomal dominant genes: EXT2, ALX4, and PHF21A.The patient was diagnosed with PSS.A total of 14 articles published in English were collected, involving this boy and other 35 patients.In these patients, 14 cases had point mutations, and 22 cases had large deletions. PHF21A gene variation was detected in 23 cases (dysgnosia in 22 cases, dyskinesia in 21 cases, language development delay in 18 cases). EXT2 gene variation was observed in 22 cases (exostoses in 13 cases). ALX4 gene variation was found in 19 cases (bilateral parietal foramina in 15 cases). Of 36 cases, 27 cases had craniofacial anomalies. Conclusions:The main clinical symptoms of PSS are language and motor developmental delay, intellectual disability, exostoses, bilateral parietal foramina, and craniofacial anomalies, which are closely related to 3 autosomal dominant genes ALX4, EXT2 and PHF21A.Genetic testing facilitates the clinical diagnosis of PSS, and the mutation types are dominated by point mutations and large deletions.

Objective:Surgical site infection (SSI) can markedly prolong postoperative hospital stay, aggravate the burden on patients and society, even endanger the life of patients. This study aims to investigate the national incidence of SSI following abdominal surgery and to analyze the related risk factors in order to provide reference for the control and prevention of SSI following abdominal surgery.Methods:A multicenter cross-sectional study was conducted. Clinical data of all the adult patients undergoing abdominal surgery in 68 hospitals across the country from June 1 to 30, 2020 were collected, including demographic characteristics, clinical parameters during the perioperative period, and the results of microbial culture of infected incisions. The primary outcome was the incidence of SSI within postoperative 30 days, and the secondary outcomes were ICU stay, postoperative hospital stay, cost of hospitalization and the mortality within postoperative 30-day. Multivariable logistic regression was used to analyze risk factors of SSI after abdominal surgery.Results:A total of 5560 patients undergoing abdominal surgery were included, and 163 cases (2.9%) developed SSI after surgery, including 98 cases (60.1%) with organ/space infections, 19 cases (11.7%) with deep incisional infections, and 46 cases (28.2%) with superficial incisional infections. The results from microbial culture showed that Escherichia coli was the main pathogen of SSI. Multivariate analysis revealed hypertension (OR=1.792, 95% CI: 1.194-2.687, P=0.005), small intestine as surgical site (OR=6.911, 95% CI: 1.846-25.878, P=0.004), surgical duration (OR=1.002, 95% CI: 1.001-1.003, P<0.001), and surgical incision grade (contaminated incision: OR=3.212, 95% CI: 1.495-6.903, P=0.003; Infection incision: OR=11.562, 95%CI: 3.777-35.391, P<0.001) were risk factors for SSI, while laparoscopic or robotic surgery (OR=0.564, 95%CI: 0.376-0.846, P=0.006) and increased preoperative albumin level (OR=0.920, 95%CI: 0.888-0.952, P<0.001) were protective factors for SSI. In addition, as compared to non-SSI patients, the SSI patients had significantly higher rate of ICU stay [26.4% (43/163) vs. 9.5% (514/5397), χ 2=54.999, P<0.001] and mortality within postoperative 30-day [1.84% (3/163) vs.0.01% (5/5397), χ 2=33.642, P<0.001], longer ICU stay (median: 0 vs. 0, U=518 414, P<0.001), postoperative hospital stay (median: 17 days vs. 7 days, U=656 386, P<0.001), and total duration of hospitalization (median: 25 days vs. 12 days, U=648 129, P<0.001), and higher hospitalization costs (median: 71 000 yuan vs. 39 000 yuan, U=557 966, P<0.001). Conclusions:The incidence of SSI after abdominal surgery is 2.9%. In order to reduce the incidence of postoperative SSI, hypoproteinemia should be corrected before surgery, laparoscopic or robotic surgery should be selected when feasible, and the operating time should be minimized. More attentions should be paid and nursing should be strengthened for those patients with hypertension, small bowel surgery and seriously contaminated incision during the perioperative period.

Objective:Surgical site infection (SSI) can markedly prolong postoperative hospital stay, aggravate the burden on patients and society, even endanger the life of patients. This study aims to investigate the national incidence of SSI following abdominal surgery and to analyze the related risk factors in order to provide reference for the control and prevention of SSI following abdominal surgery.Methods:A multicenter cross-sectional study was conducted. Clinical data of all the adult patients undergoing abdominal surgery in 68 hospitals across the country from June 1 to 30, 2020 were collected, including demographic characteristics, clinical parameters during the perioperative period, and the results of microbial culture of infected incisions. The primary outcome was the incidence of SSI within postoperative 30 days, and the secondary outcomes were ICU stay, postoperative hospital stay, cost of hospitalization and the mortality within postoperative 30-day. Multivariable logistic regression was used to analyze risk factors of SSI after abdominal surgery.Results:A total of 5560 patients undergoing abdominal surgery were included, and 163 cases (2.9%) developed SSI after surgery, including 98 cases (60.1%) with organ/space infections, 19 cases (11.7%) with deep incisional infections, and 46 cases (28.2%) with superficial incisional infections. The results from microbial culture showed that Escherichia coli was the main pathogen of SSI. Multivariate analysis revealed hypertension (OR=1.792, 95% CI: 1.194-2.687, P=0.005), small intestine as surgical site (OR=6.911, 95% CI: 1.846-25.878, P=0.004), surgical duration (OR=1.002, 95% CI: 1.001-1.003, P<0.001), and surgical incision grade (contaminated incision: OR=3.212, 95% CI: 1.495-6.903, P=0.003; Infection incision: OR=11.562, 95%CI: 3.777-35.391, P<0.001) were risk factors for SSI, while laparoscopic or robotic surgery (OR=0.564, 95%CI: 0.376-0.846, P=0.006) and increased preoperative albumin level (OR=0.920, 95%CI: 0.888-0.952, P<0.001) were protective factors for SSI. In addition, as compared to non-SSI patients, the SSI patients had significantly higher rate of ICU stay [26.4% (43/163) vs. 9.5% (514/5397), χ 2=54.999, P<0.001] and mortality within postoperative 30-day [1.84% (3/163) vs.0.01% (5/5397), χ 2=33.642, P<0.001], longer ICU stay (median: 0 vs. 0, U=518 414, P<0.001), postoperative hospital stay (median: 17 days vs. 7 days, U=656 386, P<0.001), and total duration of hospitalization (median: 25 days vs. 12 days, U=648 129, P<0.001), and higher hospitalization costs (median: 71 000 yuan vs. 39 000 yuan, U=557 966, P<0.001). Conclusions:The incidence of SSI after abdominal surgery is 2.9%. In order to reduce the incidence of postoperative SSI, hypoproteinemia should be corrected before surgery, laparoscopic or robotic surgery should be selected when feasible, and the operating time should be minimized. More attentions should be paid and nursing should be strengthened for those patients with hypertension, small bowel surgery and seriously contaminated incision during the perioperative period.