BackgroundInvasive vagus nerve stimulation therapy has been approved for the adjunctive treatment of treatment-resistant depression， which may contribute to the anti-inflammatory properties of vagus nerve stimulation （VNS）， whereas the efficacy of non-invasive transcutaneous cervical vagus nerve stimulation （tcVNS） in treating major depressive disorder （MDD） and its impact on plasma inflammatory factors remain unclear. ObjectiveTo observe the effect of escitaloprom combined with tcVNS on the status of depression， anxiety and sleep quality as well as the plasma levels of interleukin-6 （IL-6） and interleukin-10 （IL-10） in MDD patients， in order to provide references for the recovery and treatment of MDD patients. MethodsFrom August 21， 2019 to April 17， 2024， 45 patients who met the diagnostic criteria for MDD in the Diagnostic and Statistical Manual of Mental Disorders， fifth edition （DSM-5） were recruited from the psychosomatic outpatient clinic of the First Affiliated Hospital of Air Force Military Medical University. Subjects were divided into study group （n=23） and control group （n=22） using random number table method. All patients were treated with escitalopram. On this basis， study group added a 30-minute tcVNS therapy once a day for 4 weeks. While control group was given corresponding sham stimulation， and the duration of each stimulation lasted 30 seconds. Before and after 4 weeks of treatment， Hamilton Depression Scale-17 item （HAMD-17） was used to assess depressive symptoms， and HAMD-17 anxiety/somatization subfactor and insomnia subfactor were used to assess patients' anxiety/somatization symptoms and sleep quality. Levels of plasma IL-6 and IL-10 were measured by enzyme-linked immunosorbent assay （ELISA）. ResultsThe generalized estimating equation model yielded a significant time effect for HAMD-17 total score， anxiety/somatization subfactor score and insomnia subfactor score in both groups （Wald χ²=315.226， 495.481， 82.420， P<0.01）. After 4 weeks of treatment， HAMD-17 total score and anxiety/somatization subfactor score of study group were lower than those of control group， with statistically significant differences （Wald χ²=4.967， 32.543， P<0.05 or 0.01）， while no statistically significant difference was found in the insomnia subfactor score between two groups （Wald χ²=0.819， P=0.366）. Significant time effects were reported on plasma IL-6 and IL-10 levels in both groups （Wald χ²=21.792， 5.242， P<0.05 or 0.01）. Compared with baseline data， a reduction in plasma IL-6 levels was detected in both groups （Wald χ²=22.015， 6.803， P<0.01）， and an increase in plasma IL-10 levels was reported in study group （Wald χ²=5.118， P=0.024） after 4 weeks of treatment. ConclusionEscitalopram combined with tcVNS therapy is effective in improving depressive symptoms， anxiety/somatization symptoms and sleep quality in patients with MDD. Additionally， it helps reduce plasma IL-6 levels and increase IL-10 levels. ［Funded by Shaanxi Provincial Key Research and Development Program-General Project （number， 2023-YBSF-185）， www.clinicaltrials.gov number， NCT04037111］

OBJECTIVE To investigate the correlation of serum P-Tau protein and β-amyloid protein expression levels with obstructive sleep apnea syndrome(OSAS)and mild cognitive impairment(MCI)patients,and their diagnostic value.METHODS From December 2020 to December 2023,120 patients with OSAS admitted to Third Hospital of Shijiazhuang were collected as the case group.According to the diagnostic criteria for MCI,patients were grouped into OSAS without MCI group(40 cases)and OSAS with MCI group(80 cases).ELISA method was applied to detect the levels of serum P-Tau protein and β-amyloid protein.Spearman method was applied to analyze the correlation between serum P-Tau protein,β-amyloid protein,and MCI.Multivariate logistic regression was applied to analyze the influencing factors of OSAS patients with MCI.ROC curve was applied to evaluate the diagnostic efficacy of serum P-Tau protein and β-amyloid protein in OSAS patients with MCI.RESULTS The Montreal Cognitive Assessment(MoCA)score in the OSAS with MCI group was obviously lower than that in the OSAS without MCI group(P<0.05).The expression levels of P-Tau protein and β-amyloid protein in the OSAS with MCI group were obviously higher than those in the OSAS without MCI group(P<0.05).The expression levels of serum P-Tau protein and β-amyloid protein in OSAS patients were negatively correlated with MoCA score(r=-0.346,-0.565,P<0.001).Serum P-Tau protein and β-amyloid protein were risk factors for OSAS with MCI(P<0.05).The AUC of the expression levels of serum P-Tau protein,β-amyloid protein,and their combination for OSAS with MCI was 0.751,0.848,and 0.928,respectively.The combined evaluation of the two showed better results(Zcombination-P-Tau protein=4.102,P<0.001;Zcombination-β amyloid protein=2.147,P=0.032).CONCLUSION The expression of serum P-Tau protein and β-amyloid protein is upregulated in OSAS patients with MCI,they are risk factors for the development of MCI in OSAS patients.The combined detection of the two has higher diagnostic efficacy.

Objective: To establish a mouse model of lung injury induced by self-antigens and explore its pathological mechanisms to provide a reliable animal model for studying the pathogenesis of rheumatoid arthritis-associated interstitial lung disease(RA-ILD). Methods: The mice were injected intradermal with antigenemulsion made of complete freund′s adjuvant(CFA) and lung tissue protein, and the emulsion prepared with incomplete Freund′s adjuvant(IFA) was used to enhance immunity. HE staining was used to observe the histopathological changes in the mice. Masson staining was used to detect pulmonary fibrosis. The mRNA levels of rheumatoid factor(RF), krebs von den lungen-6(KL-6) and surfactant protein D(SP-D) were detected by qPCR. The levels of ACPA, IgG1, IgG2a and IgG3 antibodies were detected by ELISA. The changes of inflammatory cells and α-smooth muscle actin(α-SMA)expression in lung tissue were detected by immunofluorescence staining. The protein expression levels of Collagen I and α-SMA were detected by Western blot. The changes of immune cells were detected by flow cytometry. Results: HE staining showed that inflammatory cell infiltration increased and tissue structure changed significantly in lung tissue after the model was established by self-lung tissue antigen. Masson staining showed increased collagen deposition in lung tissue of model mice. qPCR tests revealed elevated mRNA levels of RF, KL-6 and SP-D. ELISA tests revealed elevated levels of ACPA, IgG1 and IgG3 antibodies. Immunofluorescence results showed that monocytes and T cells increased, and α-SMA expression increased in the model group. Western blot results showed increased protein expressions of Collagen Ⅰ and α-SMA. The flow cytometry results showed an increase in T cells and monocytes in the lung tissue. Conclusion The mouse model of lung injury induced by self-antigens is successfully established, and T cells and monocytes may be involved in the occurrence and progression of the disease.

ObjectiveBidirectional and two-sample Mendelian randomization（MR） method was used to investigate the bidirectional causal relationship between constipation and pneumonia and to understand the potential relationship between the two diseases from a new perspective， providing new targets for future treatment strategies. MethodConstipation and pneumonia datasets were selected from the genome-wide association study（GWAS） website for the European population in 2021. The data related to constipation included 411 623 samples， and the single nucleotide polymorphism（SNP） data were 24 176 599. The pneumonia data contained 480 299 samples with a number of SNPs of 24 174 646. In this study， inverse variance weighting（IVW） was adopted as the main analysis method of MR， supplemented by weighted median method， simple model， weighted model and MR-Egger regression analysis results， and sensitivity analysis was performed to evaluate the robustness of the results. ResultSeventeen SNPs highly correlated with constipation and 12 SNPs highly correlated with pneumonia were finally included. IVW analysis results of forward MR analysis showed that constipation increased the risk of pneumonia｛odds ratio（OR）=1.143， 95% confidence interval（CI）［1.045， 1.249］， P=0.003｝， MR-Egger regression， simple model， weighted model and weighted median analysis all supported the result（P<0.05）. IVW analysis by reverse MR analysis showed that pneumonia did not increase the risk of constipation｛OR=1.138， 95%CI［0.974， 1.329］， P=0.103｝， MR-Egger regression， simple model， weighted model and weighted median analysis also supported this result. ConclusionThe bidirectional and dual-sample MR analysis method is used to confirm the causal relationship between constipation and pneumonia from the perspective of genetic variation， while there is no obvious causal relationship on the contrary. This study will be helpful for the clinical diagnosis and treatment of constipation and pneumonia， and provide a reference for the study of the pathogenesis between the two.

Retinopathy of prematurity(ROP)is a vasoproliferative disorder of the retina,which may lead to retinal de-tachment and permanent vision loss.Timely screening and diagnosis of ROP and appropriate treatment are essential to pre-vent blindness and reduce the rate of blindness in preterm infants.In recent years,advances in optical technologies such as contact and non-contact fundus cameras,fundus fluorescein angiography,and optical coherence tomography have greatly enhanced people's ability to identify the imaging features of ROP.Based on the development of these technologies,oph-thalmologists have updated the imaging diagnostic criteria for ROP.This article reviews the application of optical imaging technology in ROP screening,in order to provide reference for clinical practice.

【Objective】 To help quality control laboratory of blood station select suitable internal quality control rules using Westgard sigma rules. 【Methods】 The accumulated coefficient of variation of internal quality control was used as the measurement imprecision in quality control laboratory of blood station, and the bias of the results of EQA in 2020 was regarded as Bias. The allowable total error (TEa) of WS/T406-2012 was used as the evaluation index to calculate the σvalue of laboratory blood testing items to select reasonable and feasible quality control rules using the Westgard sigma rule. 【Results】 The average σvalues of total protein in the three national EQAS were 14.2, 8.7 and 9.6, respectively. The average σvalues of fibrinogen in two national EQAS were 3.6 and 4.1. The average σvalues of Plt counts and MCHC were <4 and >3, and those of other items were more than 6 in two national EQAS. 【Conclusion】 The rule of 13s, 13s/22s/R4s/41s/ and 13s/22s/R4s/41s/ should be used in total protein, fibrinogen and whole blood cell count testing, respectively, by Westgard sigma rule, which can effectively help the blood quality control laboratory select appropriate quality control rules.

Objective:To investigate the effect of applying waterproof film combined with non-woven tape fixation of endotracheal tube in cleft lip and palate operation.Methods:From July 2018 to December 2018, 72 cases of cleft palate and cleft lip were selected from the operating room of the First Affiliated Hospital of Zhengzhou University The cases were randomly divided into the control group (suture and thread fixation method) and the experimental group (medical waterproof lamination combined with non-woven cloth), with 36 cases in each group. The duration of catheter fixation, intraoperative catheter fixation and postoperative catheter-related complications were compared between the two groups.Results:There were statistically significant differences between the experimental group and the control group in the duration of catheter fixation, surgeon satisfaction score and incidence of needle stab injury and needle stab bleeding: (1.15±0.63) min, (4.50±0.56), 0 case, 0 case in the experimental group, and those in the control group were (2.36±0.56) min, (3.83±1.13), 6 cases, 6 cases ( t values were 0.000, 14.435, χ2 values were 72.000, 6.545, P<0.01 or 0.05). Compared with the control group, there were no statistically significant differences in operation time, intraoperative oxygen saturation, catheter fixation direction, incidence of tube tearing, and incidence of postoperative scar ( P>0.05) in the experimental group. Conclusions:Medical waterproof film combined with non-woven tape fixed endotracheal intubation can obviously shorten the preoperative endotracheal intubation fixing time, improve the surgeon satisfaction. At the same time, it is effective in preventing postoperative complications caused by fixation with needle and silk thread.

Objective:To evaluate the effect of parecoxib sodium on phenotypic transformation of alveolar macrophages in a mouse model of ventilator-associated lung injury (VALI).Methods:Forty-five SPF healthy adult male C57BL/6J mice, weighing 22-30 g, aged 8-12 weeks, were divided into 3 groups ( n=15 each) using a random number table method: sham operation group (S group), VALI group (V group) and parecoxib sodium group (P group). Lipopolysaccharide 20 ng was intraperitoneally injected, and 2 h later the animals were mechanically ventilated (tidal volume 30 ml/kg, respiratory rate 70 breaths/min, inspiratory/expiratory ratio 1∶2, fraction of inspired oxygen 21%, positive end-expiratory pressure 0) for 4 h to establish the model of VALI.Parecoxib sodium 30 mg/kg was intravenously injected at 1 h prior to mechanical ventilation in group P. The mice were sacrificed at 4 h of ventilation, the right lung was lavaged and the broncho-alveolar lavage fluid (BALF) was collected for determination of interleukin-6 (IL-6), IL-10 and tumor necrosis factor-alpha (TNF-α) concentrations (by enzyme-linked immunosorbent assay), expression of inducible nitric oxide synthase (iNOS) and arginase-1(Arg-1) in BALF and expression of phosphorylated Janus kinase 2 (p-JAK2) and phosphorylated signal transduction and transcription activator 3 (p-STAT-3) (by Western blot). The left lung was removed for determination of the wet/dry weight ratio (W/D ratio) and for examination of the pathological changes which were scored. Results:Compared with group S, the lung injury score, W/D ratio, concentrations of IL-6, IL-10 and TNF-α in BALF, and expression of iNOS, Arg-1, p-JAK2 and p-STAT-3 were significantly increased in V and P groups ( P<0.05). Compared with group V, the concentration of IL-10 in BALF and expression of Arg-1, p-JAK2 and p-STAT-3 were significantly increased, and the lung injury score, W/D ratio, concentrations of IL-6 and TNF-α in BALF and expression of iNOS were decreased in group P ( P<0.05). Conclusion:Parecoxib sodium promotes phenotypic transformation of alveolar macrophages from M1 subtype to M2 subtype and inhibits inflammatory responses, thus alleviating VALI, which may be related to activating JAK2/STAT-3 signaling pathway in mice.

Objective To investigate the inhibitory effect of rapamycin,an mammalian target of rapamycin (mTOR) pathway inhibitor,on the proliferation,migration and fibrosis of human pterygium fibroblasts (PFBs).Methods Pterygium tissues were collected from patients with primary pterygium who underwent surgical excision in Shenyang Fourth People's Hospital from May to July 2015.The tissues were cultured in vitro and the PFBs were identified by anti-human vimentin immunofluorescence assay.The 3 to 5 generation cells were used for the experiments.The viability of cells treated with different concentrations of rapamycin was detected by methyl thiazolyl tetrazolium (MTT).The cells were divided into normal control group and rapamycin group,and the scratch wound healing test was used to evaluate migration of the PFBs.The expressions of MKI67,α-smooth muscle actin (α-SMA),fibronectin,caspase3,mammalian target of rapamycin (mTOR) and LC3B mRNA were detected by real-time quantitative PCR.Results The cultured cells showed morphology of long spindle and were vimentin immunopositive.The cell viability in rapamycin treated PFBs demonstrated a dose-dependent decrease.At 24 hours after culture,The cell viability in 30 μmol/L rapamycin group was (76.67±8.84)％ of that in 0 μmol/L rapamycin group (P＜0.001).The relative residual scratch width in 30 μ mol/L rapamycin group was (35.40±11.62) ％ 48 hours after scratch,which was significantly greater than (2.45±0.76) ％ in the normal control group (P＜0.05).Real-time quantitative PCR showed that the mRNA expressions of MKI67,α-SMA,fibronectin and mTOR in rapamycin group were significantly decreased when compared with those in normal control group (all at P＜0.05).The expression of LC3B mRNA in rapamycin group was significantly higher than that in normal control group (P＜0.05).The mRNA expression of caspase3 was not significantly different between the two groups (P=0.861).Conclusions Rapamycin can effectively inhibit the proliferation,migration and fibrosis of PFBs without affecting the cell survival.Detailed mechanism remains to be further studied.Rapamycin may serve as an anti-fibrosis agent to prevent the progression and recurrence of pterygium in the future.

Objective To investigate the inhibitory effect of rapamycin,an mammalian target of rapamycin (mTOR) pathway inhibitor,on the proliferation,migration and fibrosis of human pterygium fibroblasts (PFBs). Methods Pterygium tissues were collected from patients with primary pterygium who underwent surgical excision in Shenyang Fourth People's Hospital from May to July 2015. The tissues were cultured in vitro and the PFBs were identified by anti.human vimentin immunofluorescence assay. The 3 to 5 generation cells were used for the experiments. The viability of cells treated with different concentrations of rapamycin was detected by methyl thiazolyl tetrazolium ( MTT) . The cells were divided into normal control group and rapamycin group, and the scratch wound healing test was used to evaluate migration of the PFBs. The expressions of MKI67,α.smooth muscle actin (α.SMA), fibronectin,caspase3, mammalian target of rapamycin ( mTOR ) and LC3B mRNA were detected by real.time quantitative PCR. Results The cultured cells showed morphology of long spindle and were vimentin immunopositive. The cell viability in rapamycin treated PFBs demonstrated a dose.dependent decrease. At 24 hours after culture,The cell viability in 30μmol/L rapamycin group was (76. 67±8. 84)％ of that in 0μmol/L rapamycin group ( P<0. 001 ) . The relative residual scratch width in 30μmol/L rapamycin group was ( 35. 40 ± 11. 62 )％ 48 hours after scratch,which was significantly greater than (2. 45±0. 76)％ in the normal control group (P<0. 05). Real.time quantitative PCR showed that the mRNA expressions of MKI67,α.SMA,fibronectin and mTOR in rapamycin group were significantly decreased when compared with those in normal control group (all at P<0. 05). The expression of LC3B mRNA in rapamycin group was significantly higher than that in normal control group (P<0. 05). The mRNA expression of caspase3 was not significantly different between the two groups (P=0. 861). Conclusions Rapamycin can effectively inhibit the proliferation, migration and fibrosis of PFBs without affecting the cell survival. Detailed mechanism remains to be further studied. Rapamycin may serve as an anti.fibrosis agent to prevent the progression and recurrence of pterygium in the future.