Objectives To investigate interleukin 36γ (IL-36γ) expression, and analyze the influence of IL-36γ to CD8⁺ T cell activity in chronic obstructive pulmonary diseases (COPD) patients with secondary fungal pneumonia. Methods Peripheral blood was collected from 47 COPD patients, 39 COPD patients with secondary fungal pneumonia, and 20 controls. Bronchial alveolar lavage fluid (BALF) was isolated from 27 COPD patients with secondary fungal pneumonia. CD8⁺ T cells were purified. The levels of four IL-36 isoforms in plasma and BALF were measured by enzyme linked immunosorbent assay (ELISA). CD8⁺ T cells were stimulated with recombinant human IL-36γ. The levels of interferon γ(IFN-γ), tumor necrosis factor α(TNF-α), perforin and granzyme B in the cultured supernatants were measured by ELISA. Recombinant human IL-36γ-stimulated CD8⁺ T cells were co-cultured with NCI-H1882 cells in either direct cell-to-cell contact or Transwell^TM manner. The levels of IFN-γ, TNF-α, and lactate dehydrogenase in the cultured supernatants were assessed. The percentage of target cell death was calculated. Results Plasma IL-36α, IL-36β, and IL-36γ levels were significantly elevated in both COPD group and COPD with secondary fungal pneumonia group compared with those in control group. However, only plasma IL-36γ level was higher in COPD with secondary fungal pneumonia group than that in COPD group [(200.11±99.95)pg/mL vs (53.03±87.18)pg/mL, P=0.023]. There was no remarkable difference in plasma IL-36 receptor antagonist level among three groups. IL-36γ level in BALF from infectious site was higher than that from non-infectious site in COPD with secondary fungal pneumonia group [(305.82±59.60)pg/mL vs (251.93±76.01)pg/mL, P=0.011]. IL-36γ stimulation enhanced IFN-γ, TNF-α, perforin and granzyme B secreted by CD8⁺ T cells. When IL-36γ-stimulated CD8⁺ T cells were directly mixed with NCI-H1882 cells for co-culture, the percentage of cell death was increased [(16.06±3.67)% vs (11.47±2.36)%, P=0.002]. When using Transwell^TM plate for non-contact co-culture, IL-36γ-stimulated CD8⁺ T cell-mediated death of NCI-H1882 cells showed no significant difference compared to that without stimulation [(4.77±0.78)% vs (4.99±0.92)%, P=0.554]. Conclusion IL-36γ level in plasma and infectious site is elevated in COPD patients with secondary fungal pneumonia, which enhances the cytotoxicity of CD8⁺ T cells in peripheral blood and infectious microenviroment.
Humans ; Pulmonary Disease, Chronic Obstructive/complications* ; CD8-Positive T-Lymphocytes/metabolism* ; Male ; Female ; Aged ; Middle Aged ; Interferon-gamma/metabolism* ; Interleukin-1/metabolism* ; Tumor Necrosis Factor-alpha/metabolism* ; Lung Diseases, Fungal/complications* ; Bronchoalveolar Lavage Fluid/chemistry* ; Perforin/metabolism* ; Pneumonia/immunology* ; Granzymes/metabolism*

Objective To investigate the spatiotemporal distribution characteristics and potential influencing factors of newly diagnosed echinococcosis cases in Qinghai Province from 2016 to 2022, so as to provide insights into the formulation of the echinococcosis control strategy in Qinghai Province. Methods The number of individuals screened for echinococcosis, number of newly diagnosed echinococcosis cases, number of registered dogs and number of stray dogs were captured from the annual reports of echinococcosis control program in Qinghai Province from 2016 to 2022, and the detection of newly diagnosed echinococcosis cases was calculated. The number of populations, precipitation, temperature, wind speed, sunshine hours, average altitude, number of year-end cattle stock, number of year-end sheep stock, gross domestic product (GDP) per capita, and number of village health centers in each county (district) of Qinghai Province were captured from the Qinghai Provincial Statistical Yearbook, and county-level electronic maps in Qinghai Province were downloaded from the National Platform for Common Geospatial Information Services. The software ArcGIS 10.8 was used to map the distribution of newly diagnosed echinococcosis cases in Qinghai Province, and the spatial autocorrelation analysis of newly diagnosed echinococcosis cases was performed. In addition, the spacetime scan analyses of number of individuals screened for echinococcosis, number of newly diagnosed echinococcosis cases and geographical coordinates in Qinghai Province were performed with the software SaTScan 10.1.2, and the spatial stratified heterogeneity of the detection of newly diagnosed echinococcosis cases was investigated with the software GeoDetector. Results A total of 6 569 426 residents were screened for echinococcosis in Qinghai Province from 2016 to 2022, and 5 924 newly diagnosed echinococcosis cases were found. The detection of newly diagnosed echinococcosis cases appeared a tendency towards a decline over years from 2016 to 2022 (χ² = 11.107, P < 0.01), with the highest detection in Guoluo Tibetan Autonomous Prefecture in 2017 (82.12/10⁵). There were spatial clusters in the detection of newly diagnosed echinococcosis cases in Qinghai Province from 2016 to 2018 (Moran’s I = 0.34 to 0.65, all Z values > 1.96, all P values < 0.05), and the distribution of newly diagnosed echinococcosis cases appeared random distribution from 2019 to 2022 (Moran’s I = −0.09 to 0.04, all Z values < 1.96, all P values > 0.05). Local spatial autocorrelation analysis showed high-high clusters and low-low clusters in the detection of new diagnosed echinococcosis cases in Qinghai Province from 2016 to 2022, and space-time scan analysis showed that the first most likely cluster areas of newly diagnosed echinococcosis cases in Qinghai Province from 2016 to 2022 were mainly distributed in Yushu Tibetan Autonomous Prefecture and Guoluo Tibetan Autonomous Prefecture. GeoDetector-based analysis of the driving factors for the spatial stratified heterogeneity of detection of newly diagnosed echinococcosis cases in Qinghai Province showed that average altitude, number of village health centers, number of cattle and sheep stock, GDP per capita, annual average sunshine hours, and annual average temperature had a strong explanatory power for the spatial distribution of newly diagnosed echinococcosis cases, with q values of 0.630, 0.610, 0.600, 0.590, 0.588, 0.537 and 0.526, respectively. Conclusions The detection of newly diagnosed echinococcosis cases appeared a tendency towards a decline in Qinghai Province over years from 2016 to 2022, showing spatial clustering. Targeted control measures are required in cluster areas of newly diagnosed echinococcosis cases for further control of the disease.

【Objective】 To investigate the development of adaptability in children aged 2 - 6, and to explore its influencing factors, so as to provide reference for promoting the development of adaptability in young children. 【Methods】 Data were from the National Nutrition and Health Systematic Survey for Children in China, and 3 319 children aged 2 - 6 and their parents from 28 sites across 14 provinces were recruited in this study.The Development Scale for Children Aged 0 - 6 years (WS/T 580-2017) was used to measure the developmental quotient of children′s adaptive ability, and a survey questionnaire was used to collect relevant information about children and their parents. 【Results】 Among 3 319 children aged 2 - 6, the proportion of slightly low or low level of adaptability, moderate adaptability development, good and excellent adaptability development was 7.68%,66.25% and 26.06%, respectively.The proportion of children aged 5 - 6 with good and excellent adaptability was lower in 3-year-old and 4-year-old groups (χ²=59.29, P<0.05).Multiple stepwise linear regression showed that children′s gender (β=0.06), gestational age of birth (β=-0.05), only child (β=-0.04), left-behind child (β=-0.04), the main caregiver (β=-0.06), and the education level of parents (β=0.09, 0.10), whether parents actively pay attention to children′s emotions (β=-0.06) and whether children play with homemade toys (β=-0.04) were the influencing factors of children′s adaptive development quotient.Girls, full-term children, only children, non-left-behind children, children with parents as main caregivers, parents with a high level of education, parents who often take the initiative to pay attention to children′s emotions, and children who play with homemade toys had a higher level of adaptability development quotient. 【Conclusions】 The development level of adaptability in children aged 2 - 6 in China is mostly above the average level and is related to multiple factors.Targeted intervention work can be carried out on relevant factors in order to promote the development of children′s adaptability.

Objective:To evaluate the efficacy of ultrasound-guided semispinalis capitis plane (SCP) block for treatment of occipital neuralgia (ON).Methods:This was a prospective study. Ninety patients of both sexes, aged 29-66 yr, suffering ON for 3 months-6 yr in Zibo Municipal Hospital from January 2022 to December 2023, were divided into 3 groups ( n=30 each) using a random number table method: combination of greater occipital nerve (GON) block and the third occipital nerve (TON) block group (group GT), SCP block via the medial head of semispinalis capitis muscle (SCM) group (group Sm), and SCP block via the space between obliquus capitis inferior and C 2, 3 facet joint (OCI-C 2, 3) group (group OC). In GT group, the analgesic and anti-inflammatory compound solution 2.5 ml was injected around GON in the SCM-OCI space at the C 2 level of the cervical vertebra and at the lateral surface of C 2, 3 facet joint. In Sm group, the analgesic and anti-inflammatory compound solution 5 ml was injected into the medial head of SCM at the level of C 1. In OC group, the analgesic and anti-inflammatory compound solution 5 ml was injected into the OCI-C 2, 3 space in the deep part of SCM. The Visual Analogue Scale (VAS) score and Pittsburgh Sleep Quality Index (PSQI) score were recorded before treatment (T 1) and at 1, 3, 7, 10 and 14 days after treatment (T 2-6), and then the rates of pain relief and improvement in sleep quality were calculated. The time spent in blocking, onset time of blocking, completion time of blocking, duration of block, and occurrence of adverse reactions within 24 h after block were recorded. Results:There were no significant differences in VAS scores and PSQI scores at T 1-3 and T 5-6 among the three groups ( P>0.05), and VAS and PSQI scores were significantly higher at T 4 in Sm group than in OC and GT groups ( P<0.05). Compared with GT group, the time spent in blocking was significantly shortened, the onset time and completion time of block was prolonged, and the duration of block was shortened in Sm group, and the time spent in blocking was significantly shortened, the onset time and completion time of block was shortened ( P<0.05), and no significant change was found in the duration of block in OC group ( P>0.05). No severe complications were observed in the three groups. Conclusions:Compared with the combination of GON and TON blocks, ultrasound-guided SCP block for treating ON is simple and highly safe, SCP block via the OCI-C 2, 3 space has rapid onset and long duration, leading to significant improvements in pain and sleep quality, and it can be used as the first-choice block method for treating ON.

Objective:To investigate the diagnostic accuracy of serological indicators and evaluate the diagnostic value of a new established combined serological model on identifying the minimal hepatic encephalopathy (MHE) in patients with compensated cirrhosis.Methods:This prospective multicenter study enrolled 263 compensated cirrhotic patients from 23 hospitals in 15 provinces, autonomous regions and municipalities of China between October 2021 and August 2022. Clinical data and laboratory test results were collected, and the model for end-stage liver disease (MELD) score was calculated. Ammonia level was corrected to the upper limit of normal (AMM-ULN) by the baseline blood ammonia measurements/upper limit of the normal reference value. MHE was diagnosed by combined abnormal number connection test-A and abnormal digit symbol test as suggested by Guidelines on the management of hepatic encephalopathy in cirrhosis. The patients were randomly divided (7∶3) into training set ( n=185) and validation set ( n=78) based on caret package of R language. Logistic regression was used to establish a combined model of MHE diagnosis. The diagnostic performance was evaluated by the area under the curve (AUC) of receiver operating characteristic curve, Hosmer-Lemeshow test and calibration curve. The internal verification was carried out by the Bootstrap method ( n=200). AUC comparisons were achieved using the Delong test. Results:In the training set, prevalence of MHE was 37.8% (70/185). There were statistically significant differences in AMM-ULN, albumin, platelet, alkaline phosphatase, international normalized ratio, MELD score and education between non-MHE group and MHE group (all P<0.05). Multivariate Logistic regression analysis showed that AMM-ULN [odds ratio ( OR)=1.78, 95% confidence interval ( CI) 1.05-3.14, P=0.038] and MELD score ( OR=1.11, 95% CI 1.04-1.20, P=0.002) were independent risk factors for MHE, and the AUC for predicting MHE were 0.663, 0.625, respectively. Compared with the use of blood AMM-ULN and MELD score alone, the AUC of the combined model of AMM-ULN, MELD score and education exhibited better predictive performance in determining the presence of MHE was 0.755, the specificity and sensitivity was 85.2% and 55.7%, respectively. Hosmer-Lemeshow test and calibration curve showed that the model had good calibration ( P=0.733). The AUC for internal validation of the combined model for diagnosing MHE was 0.752. In the validation set, the AUC of the combined model for diagnosing MHE was 0.794, and Hosmer-Lemeshow test showed good calibration ( P=0.841). Conclusion:Use of the combined model including AMM-ULN, MELD score and education could improve the predictive efficiency of MHE among patients with compensated cirrhosis.

Objective: This cross-sectional investigation aimed to determine the incidence, clinical characteristics, prognosis, and related risk factors of olfactory and gustatory dysfunctions related to infection with the SARS-CoV-2 Omicron strain in mainland China. Methods: Data of patients with SARS-CoV-2 from December 28, 2022, to February 21, 2023, were collected through online and offline questionnaires from 45 tertiary hospitals and one center for disease control and prevention in mainland China. The questionnaire included demographic information, previous health history, smoking and alcohol drinking, SARS-CoV-2 vaccination, olfactory and gustatory function before and after infection, other symptoms after infection, as well as the duration and improvement of olfactory and gustatory dysfunction. The self-reported olfactory and gustatory functions of patients were evaluated using the Olfactory VAS scale and Gustatory VAS scale. Results: A total of 35 566 valid questionnaires were obtained, revealing a high incidence of olfactory and taste dysfunctions related to infection with the SARS-CoV-2 Omicron strain (67.75%). Females(χ2=367.013, P<0.001) and young people(χ2=120.210, P<0.001) were more likely to develop these dysfunctions. Gender(OR=1.564, 95%CI: 1.487-1.645), SARS-CoV-2 vaccination status (OR=1.334, 95%CI: 1.164-1.530), oral health status (OR=0.881, 95%CI: 0.839-0.926), smoking history (OR=1.152, 95%CI=1.080-1.229), and drinking history (OR=0.854, 95%CI: 0.785-0.928) were correlated with the occurrence of olfactory and taste dysfunctions related to SARS-CoV-2(above P<0.001). 44.62% (4 391/9 840) of the patients who had not recovered their sense of smell and taste also suffered from nasal congestion, runny nose, and 32.62% (3 210/9 840) suffered from dry mouth and sore throat. The improvement of olfactory and taste functions was correlated with the persistence of accompanying symptoms(χ2=10.873, P=0.001). The average score of olfactory and taste VAS scale was 8.41 and 8.51 respectively before SARS-CoV-2 infection, but decreased to3.69 and 4.29 respectively after SARS-CoV-2 infection, and recovered to 5.83and 6.55 respectively at the time of the survey. The median duration of olfactory and gustatory dysfunctions was 15 days and 12 days, respectively, with 0.5% (121/24 096) of patients experiencing these dysfunctions for more than 28 days. The overall self-reported improvement rate of smell and taste dysfunctions was 59.16% (14 256/24 096). Gender(OR=0.893, 95%CI: 0.839-0.951), SARS-CoV-2 vaccination status (OR=1.334, 95%CI: 1.164-1.530), history of head and facial trauma(OR=1.180, 95%CI: 1.036-1.344, P=0.013), nose (OR=1.104, 95%CI: 1.042-1.171, P=0.001) and oral (OR=1.162, 95%CI: 1.096-1.233) health status, smoking history(OR=0.765, 95%CI: 0.709-0.825), and the persistence of accompanying symptoms (OR=0.359, 95%CI: 0.332-0.388) were correlated with the recovery of olfactory and taste dysfunctions related to SARS-CoV-2 (above P<0.001 except for the indicated values). Conclusion: The incidence of olfactory and taste dysfunctions related to infection with the SARS-CoV-2 Omicron strain is high in mainland China, with females and young people more likely to develop these dysfunctions. Active and effective intervention measures may be required for cases that persist for a long time. The recovery of olfactory and taste functions is influenced by several factors, including gender, SARS-CoV-2 vaccination status, history of head and facial trauma, nasal and oral health status, smoking history, and persistence of accompanying symptoms.
Female ; Humans ; Adolescent ; SARS-CoV-2 ; Smell ; COVID-19/complications* ; Cross-Sectional Studies ; COVID-19 Vaccines ; Incidence ; Olfaction Disorders/etiology* ; Taste Disorders/etiology* ; Prognosis

Aim To investigate the effects of dagliflozin (DAPA) on atrial tachyarrhythmia (AT) in rats with right heart failure (RHF) due to pulmonary arterial hypertension (PAH) and the underlying mechanisms. Methods Sixty male SD rats were randomly divided into four groups: control group (CTL group), model group (MCT group), MCT + low-dose DAPA intervention group (MCT + LD group) and MCT + high-dose DAPA intervention group (MCT + HD group). After 35 days of continuous intervention, the model and cardiac function evaluation, atrial structural remodelling assessment, inflammatory factor detection, and in vivo cardiac electrophysiology experiments were completed. Results DAPA reduced menn pulmonaryarterial pressure (mPAP) and menn right ventricular pressure (mRVP) in the model rats (P <0.05), attenuated the inflammatory response (P < 0.05), reduced right atrial fibrosis (P <0.05), reduced AT induction rate (P < 0.05) and mean atrial tachyarrhythmia duration (MATD) (P < 0.05), the extent of which was more pronounced in the high-dose DAPA intervention group. Conclusions DAPA can reduce AT susceptibility in PAH-induced RHF rats, and the mechanisms may be related to the inhibition of systemic inflammation and anti-atrial fibrosis by DAPA.

Aim To investigate the effect of silencing circRNA ciRS-7 on cisplatin resistance of gastric cancer cells and its related mechanism. Methods Cisplatin-resistant gastric cancer cells HGC-27/DDP were constructed, ciRS-7 was silenced and HGC-27/DDP cells were treated with cisplatin. Real-time quantitative PCR (qRT-PCR) was used to detect the expression levels of ciRS-7 and microrNA-944 (miR-944). Cell counting kit-8 (CCK-8) was used to detect cell survival rate. Clone formation assay was used to detect the number of clones. Western blot was used to detect the protein expression levels of CyclinD1, proliferating cell nuclear antigen (PCNA), B-lymphocytoma-2-associated X protein (Bax), B-lymphocytoma-2 (Bcl-2) and cleaved aspartate-specific cysteine proteinase 3 (cleaved-caspase-3). Flow cytometry was used to detect cell apoptosis rate. In situ end labeling (TUNEL) was used to detect apoptosis index. Dual luciferase assay was used to verify the targeting relationship between ciRS-7 and miR-944. Results CiRS-7 was highly expressed in cisplatin-resistant gastric cancer tissues and cells, while miR-944 was low expressed in cisplatin-resistant gastric cancer tissues and cells. The survival rate, clonal formation number, protein expression levels of CyclinD1, PCNA and Bcl-2 in cisplatin-treated HGC-27/DDP cells were significantly reduced by silencing ciRS-7, while ciRS-7 expression level, apoptosis rate, apoptosis index, Bax, cleaved-caspase-3 protein expression levels of cisplatin-treated HGC-27/DDP cells were significantly raised. CiRS-7 targetedly inhibited the expression of miR-944. Conclusions Silencing ciRS-7 can reverse cisplatin resistance of gastric cancer cells, and the mechanism may be related to the promotion of miR-944 expression by silencing ciRS-7.

Objective To investigate the effect of exosomes derived from Echinococcus multilocularis on macrophage polarization after treatment for different durations and concentrations. Methods A total of 60 BALB/c mice were used for modeling, among which 4 mice were selected to observe the growth of abdominal lesions on 7.0T MRI. The mice for modeling were dissected, and the protoscoleces was taken from the abdominal lesion and cultured in vitro ; ultracentrifugation was used to extract the exosomes from the supernatant, and transmission electron microscopy and Western blotting were used for the characterization of exosomes. The macrophages without exosome treatment were established as control group, and the macrophages co-cultured with different concentrations of exosomes derived from Echinococcus multilocularis were established as experimental group (10 μg/mL group and 50 μg/mL group) and were cultured for 48 and 72 hours. The morphological changes of macrophages were observed under a microscope, and flow cytometry and ELISA were used to observe polarization state. A one-way analysis of variance was used for comparison of normally distributed continuous data between multiple groups, and the least significant difference t -test was used for further comparison between two groups. Results The results of 7.0T MRI showed the formation of diffuse lesions with different sizes in the abdominal cavity of mice, and the exosomes derived from Echinococcus multilocularis were approximately 100 nm in diameter and were cup-shaped or saucer-shaped, with the positive expression of the surface markers CD9, TSG101, and CD63. After co-culture, most of the cells in the experimental group were elongated with an irregular and polygonal shape. Flow cytometry showed that after 48 hours of co-culture, the positive rates of CD16/32, CD206, and CD369 in the control group were 99.53%±0.06%, 90.27%±0.21%, and 2.40%±0.20%, respectively; compared with the control group, except that the 10 μg/mL exosome group had a significant reduction in the positive rate of CD369 (0.80%±0.00%) ( P < 0.05), all the other groups had a significant increase in the positive rates of CD16/32, CD206, and CD369 (all P < 0.000 1); after 72 hours of co-culture, the positive rates of CD16/32, CD206, and CD369 in the control group were 99.67%±0.06%, 85.47%±0.55%, and 6.60%±0.20%, respectively, and compared with the control group, the experimental group had significant increases in the positive rates of CD16/32, CD206, and CD369 (all P < 0.05). ELISA showed that after 48 hours of co-culture, the levels of IL-6 and TNFα in the control group were 58.53±15.52 pg/mL and 320.70±5.30 pg/mL, respectively, and when the exosome concentration was 50 μg/mL, the level of IL-6 in the experimental group was 98.81±15.55 pg/mL, which was higher than that in the control group ( P < 0.05); after 72 hours of co-culture, the levels of IL-6 and TNFα in the control group were 76.22±9.68 pg/mL and 323.90±87.37 pg/mL, respectively, and when the exosome concentration was 10 μg/mL, the level of TNFα was 164.20±14.17 pg/mL, which was significantly lower than that in the control group ( P < 0.05); when the exosome concentration was 50 μg/mL, the level of IL-6 was 99.52±8.35 pg/mL, which was significantly higher than that in the control group ( P < 0.05). Conclusion Exosomes derived from Echinococcus multilocularis can regulate macrophage polarization and induce M2-like polarization of macrophages after co-culture at a concentration of 10 μg /mL for 72 hours, and further studies are needed to clarify the specific method.