Objective:To explore the role of fibroblast growth factor 21 (FGF21) in rats with severe acute pancreatitis-associated acute lung injury (SAP-ALI) and its related molecular mechanisms.Methods:Twenty-four healthy male SD rats were randomly divided into 4 groups (random number, n=6 per group): Control group, SAP group, FGF21 intervention group (SAP+FGF21 group), and autophagy inhibitor group (SAP+FGF21+3-MA group). The SAP model was established by retrograde injection of 3.5% sodium taurocholate into the pancreatic duct. In SAP+FGF21 group, FGF21 10 mg/kg was intraperitoneally injected at 1 hour before modeling. In SAP+FGF21+3-MA group, FGF21 10 mg/kg and 3-MA 20 mg/kg were intraperitoneally injected at 1 h before modeling. Serum amylase activity was detected by biochemical kit. Plasma levels of tumor necrosis factor alpha (TNF-α) and FGF21 were detected by ELISA. HE staining was used to observe the pathological changes of pancreas and lung tissues. Immunofluorescence was used to detect the protein level of FGF21 in lung tissue. Western blot was used to detect the expression levels of autophagy-related proteins in lung tissue. Autophagosomes in lung tissue were observed by electron microscopy. Results:Compared with the Control group, the plasma and lung tissue FGF21 levels in SAP group were significantly decreased (both P<0.001) , severe pancreatic and lung tissue damage, and elevated plasma TNF-α levels ( P<0.001). Western Blot and transmission electron microscopy showed that: The expression of LC3Ⅱ/Ⅰ in lung tissue of SAP group was down-regulated [(0.912±0.052) vs. (0.700±0.135), P<0.001], and P62 protein level was up-regulated [(0.475±0.068) vs. (0.687±0.070), P<0.001] , and reduced autophagosome counts in the SAP group. In contrast, the SAP+FGF21 group showed elevated FGF21 levels (both P<0.01), attenuated pancreatic and lung injury ( P<0.001), decreased TNF-α levels [(280.10±49.36) pg/mL vs. (86.32±66.00) pg/mL, P<0.001]. Lung tissue of LC3 Ⅱ/Ⅰ levels increase [(0.700±0.135) vs. (0.853±0.073), P<0.01], P62 protein levels cut [(0.687±0.070) vs. (0.538±0.030), P<0.01] ], and increased autophagosomes and autolysosomes under electron microscopy. Compared with SAP+FGF21 group, the expression levels of FGF21 in plasma and lung tissue in SAP+FGF21+3-MA group were not significantly changed, and the level of autophagy was decreased. Pancreas and lung tissue injury was severe ( P<0.001), Plasma TNF-α level obviously higher [(86.32±66.00) pg/mL vs. (212.90±11.56) pg/mL, P<0.05]. Conclusion:FGF21 may play a protective role in SAP-ALI by up-regulating the level of autophagy.

Objective: To explore the therapeutic mechanism of puerarin in treating rheumatoid arthritis (RA) rats based on the serine/tyrosine protein kinase B (AKT)-phosphorylated forkhead box protein O1 (FOXO1)-interleukin-9 (AKT-FOXO1-IL-9) signaling pathway. Methods : 36 rats were randomly divided into a blank group , a model group , a positive control group , and low , medium , and high dose groups of puerarin. Except for the blank group , the other groups were induced with type Ⅱ collagen to establish a RA rat model. After successful modeling , different doses of puerarin and methotrexate were given to treat the rats. The body mass and toe thickness of the rats were measured , and biochemical indicators of rat blood rheology were detected. X-ray was used to observe changes in rat joint morphology. Safranin green staining were used to observe the pathology of rat joint tissue. ELISA was used to detect the levels of IL-9 and rheumatoid factors in rat serum , and Western blot was used to detect changes in levels of AKT and FOXO1 . 36 rats were randomly divided into a blank group , a model group , a positive control group , and low , medium , and high dose groups of puerarin. Except for the blank group , the other groups were induced with type Ⅱ collagen to establish a RA rat model. After successful modeling , different doses of puerarin and methotrexate were given to treat the rats. The body mass and toe thickness of the rats were measured , and biochemical indicators of rat blood rheology were detected. X-ray was used to observe changes in rat joint morphology. Safranin green staining were used to observe the pathology of rat joint tissue. ELISA was used to detect the levels of IL-9 and rheumatoid factors in rat serum , and Western blot was used to detect changes in levels of AKT and FOXO1 . Results: Compared with the blank group , the model group had the lowest toe thickness , and X-ray images showed more obvious segmental stenosis and more severe marginal bone invasion ; scaly like changes appeared at the edges of joints stained with safranin green , accompanied by the exudation of inflammatory cells and increased proliferation and secretion of chondrocytes ; the expression levels of inflammatory factors IL-9 and rheumatoid factors were the highest , and the expression levels of AKT and FOXO1 proteins were the highest (P < 0. 05) . Compared with the model group , the toe thickness of rats treated with different doses of puerarin decreased ; X-ray images showed that the puerarin treatment group of rats showed improvement in plantar joint stenosis and marginal bone invasion ; the results of safranin green staining showed that after treatment with different doses of puerarin , the infiltration of inflammatory cells decreased , and the expression levels of inflammatory factor IL-9 , rheumatoid factors , AKT , and FOXO1 proteins decreased significantly ( P < 0. 05 ) , with the high-dose puerarin group showing the most significant difference. Compared with the high-dose puerarin group , the positive control group showed a significant decrease in the above results and statistical differences (P < 0. 05) . Conclusion Puerarin has a good therapeutic effect on rats with RA by inhibiting the AKT-FOXO1-IL-9 pathway. The high-dose puerarin group (60 mg/kg) has the best therapeutic effect and the results show a dose-response relationship.

Objective:To study the population distribution of Pomacea spp. in Shandong Province and the risk of angiostrongyliasis cantonensis in the local population, and to provide a basis for scientific prevention and control of related diseases. Methods:From July to December 2021, Yanzhou District of Jining City, Ningyang County of Taian City, and Dongying District of Dongying City were selected as surveillance sites to investigate the population and distribution range of Pomacea spp., live snail samples were collected for morphological and genetic identification, and Pomacea spp. infected with the larva of Angiostrongylus cantonensis was detected by lung test. At the same time, sentinel hospital case surveillance was carried out in Yanzhou District, Jining City, and questionnaire was used to study the local residents' awareness of angiostrongyliasis cantonensis and their personal health behaviors. Results:A total of 312 live snail samples were collected. After morphological identification, they were all Pomacea spp.. After gene sequencing, two populations of Pomacea canaliculata and Pomacea maculata were found. No positive snails infected with Angiostrongylus cantonensis were found. A total of 126 patients with headache as the main neurological symptom were admitted to the sentinel hospital, but there were no monitoring cases that met the inclusion criteria. Among the survey population, 48.38% (134/277) of the respondents had heard of angiostrongyliasis cantonensis, 44.77% (124/277) knew that eating Margarya melanioides might cause angiostrongyliasis cantonensis, and 83.39% (231/277) had no related unhealthy eating behavior. Conclusion:Pomacea spp. is found and reported for the first time in Shandong Province, and there is a risk of population infection with angiostrongyliasis cantonensis.

Acute pancreatitis (AP) is a common and potentially threatening disease of the pancreas, and some patients eventually develop to severe acute pancreatitis (SAP). Symptomatic support therapies such as rehydration therapy and anti-infection are still the main treatments. Lacking specific therapies is the main reason for the high mortality of AP patients, especially those with SAP. Premature trypsinogen activation is the most important pathologic cellular event in the pathogenesis of AP. The release of trypsin can cause self-digestion inside and outside of acinar cells, especially the release of cathepsin B can also cause a caspase-unrelated regulatory cell death (RCD) known as necroptosis, which is closely related to the development and prognosis of AP. Therefore, it is necessary to further study the mechanism of necroptosis in the occurrence and development of AP. This article reviews the mechanism of necroptosis and the research progress related to AP, in an attempt to provide a new understanding of the pathogenesis and treatment of AP, and promote the better target drug development.

Objective To explore the temporal and spatial distribution characteristics of air pollutants PM_2.5, PM₁₀, SO₂, CO, and NO₂, and their effects on acute cerebrovascular diseases in Jining City. Methods The data of patients with acute cerebrovascular disease treated in a 3A hospital in Jining from October 1, 2017, to November 31, 2019, were retrospectively collected. Combined with the air pollution data of 29 air quality monitoring stations in Jining City, the Kriging interpolation model was used to analyze the overall situation of air pollution in Jining. On this basis, the relationship between air pollution and acute cerebrovascular diseases in Jining City was analyzed. Results In Jining City, the incidence of acute cerebrovascular disease in male was higher than that in female, and the incidence in rural areas was significantly higher than that in urban areas. The spatial distribution showed a trend of gradual accumulation from southeast to northwest. The daily average concentrations of PM2.5 and PM10 were higher in winter and spring than in summer and autumn. The results of Kriging interpolation analysis showed that the concentrations of these air pollutants formed aggregation points in varying degrees. The spatial distribution of acute cerebrovascular disease patients in Jining City was highly consistent with the spatial distribution of air pollutant concentrations. Spearman correlation analysis showed that CO, SO₂, and NO₂ were positively correlated with the incidence of acute cerebrovascular disease, while the correlation between PM_2.5 and PM₁₀ and the incidence of acute cerebrovascular disease was not significant. Conclusion Some air pollutants such as CO, SO₂, and NO₂ have a positive correlation with the incidence of acute cerebrovascular disease, and the prevalence has a certain population and regional distribution. In the future work of cerebrovascular disease prevention, personal protection should be done according to local conditions and living environment of specific people.

Objective:To investigate the predictive value of the ischemic stroke predictive risk score (iScore) and serum homocysteine (Hcy) for early neurological deterioration (END) in patients with acute ischemic stroke.Methods:Patients with acute ischemic stroke admitted to the Affiliated Hospital of Jining Medical University from July 2018 to June 2020 were enrolled retrospectively. END was defined as the National Institutes of Health Stroke Scale (NIHSS) score within 7 d after admission increased by ≥2 from the baseline. Multivariate logistic regression analysis was used to determine the independent correlations of iScore and serum Hcy level with END, and then the receiver operating characteristics (ROC) curve was used to evaluate the individual and combined predictive values of iScore and serum Hcy for END. Results:A total of 398 patients with acute ischemic stroke were enrolled, including 241 (60.6%) males, aged 65.02±12.17 years. The baseline NIHSS score was 12.15±5.67 and iScore was 124.58±37.51, and 103 patients (25.9%) developed END. Univariate analysis showed that there were significant differences in atrial fibrillation, fasting blood glucose, serum Hcy, stroke etiology type (large artery atherosclerosis and small artery occlusion), baseline NIHSS score and iScore between the END group and the non-END group (all P<0.05). Multivariate logistic regression analysis showed that after adjusting for age, atrial fibrillation, fasting blood glucose, and stroke etiology type, the iScore (odds ratio [ OR] 1.016, 95% confidence interval [ CI] 1.009-1.040; P=0.004), serum Hcy ( OR 1.191, 95% CI 1.075-1.588; P<0.001) and baseline NIHSS score ( OR 1.289, 95% CI 1.101-1.613; P=0.023) had significant independent correlation with END. ROC curve analysis showed that the area under the curve of iScore combined with serum Hcy for predicting END was 0.859 (95% CI 0.820-0.898; P<0.001), which was significantly higher than that of iScore or serum Hcy alone ( P<0.001). The sensitivity and specificity of combined prediction were 81.55% and 85.76%, respectively. Conclusion:The iScore combined with serum Hcy has higher predictive value for END in patients with acute ischemic stroke.

Objective:To analyze the clinical characteristics and treatment of tricuspid valve prolapse caused by chordal rupture complicated with persistent pulmonary hypertension in neonates.Methods:The clinical data of a male neonate with tricuspid valve prolapse complicated with persistent pulmonary hypertension admitted to the Neonatal Intensive Care Unit of Children′s Hospital of Hebei Province in November 2018 was analyzed retrospectively. Related literature up to September 2020 was searched with the strategy of "(neonate OR newborn) AND (tricuspid valve prolapse) AND (rupture OR necrosis) AND (papillary muscle OR chordae tendineae) AND (pulmonary hypertension)" in Wanfang, CNKI and PubMed database in Chinese and English. The characteristics of the disease were summarized.Results:A male full-term neonate was admitted due to presenting severe cyanosis for 9 hours. He was born by caesarean section and presented severe cyanosis and dyspnea at 10 min of ages, unresponsive to the positive airway pressure resuscitation. After 9 hours of mechanical ventilation, there was no improvement. Thus he was transferred to Children′s Hospital of Hebei Province. On admission, the initial blood gas analysis showed an arterial partial pressure of oxygen of 22.5 mmHg (1 mmHg=0.133 kPa). The echocardiography revealed prolapsed anterior leaflet of tricuspid valve, severe tricuspid regurgitation (TR) and pulmonary artery hypertension, and right to left shunt via a patent foramen ovale. The arterial duct was closed. The chest X-ray was normal. The boy was treated with nitric oxide, milrinone, and continued mechanical ventilation initially. Addition of prostacyclin analog (treprostinil) on day 3 led to significant improvement of pulmonary blood flow, oxygenation, and stabilization, so that the extracorporeal membrane oxygenation therapy was avoided. At 11 months after birth, the boy underwent cardiac surgery. At surgery, the rupture of chordal tendineae in anterior leaflet of tricuspid valve was found. Tricuspid annuloplasty, valvuloplasty and repair of patent foramen ovale were successfully performed. The follow-up echocardiogram at postoperative 3 months showed only mild tricuspid insufficiency. The boy was well at last follow-up at 22 months of age with normal cognitive skill development. According to literature, 20 cases of papillary muscle or chordae tendineae rupture in neonates had been reported in 12 English papers. Among the total 21 neonates, there were 12 male infants and only one premature infant with gestational age of 33 weeks. They presented with profound cyanosis soon after birth. All of them received endotracheal intubation and mechanical ventilation. Other treatments included inhalation of nitric oxide, intravenous milrinone, vasoactive drugs, diuretics and prostacyclin, etc. Extracorporeal membrane oxygenation (ECMO) was used in 6 infants as a bridge to surgical treatment. Two cases reported earlier death of cardiopulmonary failure without operation and the rest 19 survived after surgery. The followed surgery or autopsy revealed that all of them had tricuspid valve prolapse, rupture of papillary muscle or chordae tendineae.Conclusions:The severe TR resulting from rupture of papillary muscle or chordate tendineae in neonates is rare and could cause severe hypoxemia. Early recognition, adequate cardiopulmonary support to stabilize the hemodynamic status and timely surgery can significantly reduce the mortality.

Objective: To evaluate the efficacy and safety of ultrafiltration in patients with heart failure. Methods: One hundred and thirty four cases of patients with heart failure, who hospitalized in our hospital from June 2010 to June 2016 were enrolled in this study. Random serial number was generated using SPSS 22.0 software, patients were then randomly divided into control group and ultrafiltration group with the proportion of 1∶1 (67 cases in each group). Patients in the control group received standard therapy. Patients in the ultrafiltration group received ultrafiltration therapy for 8 hours. Curative effect was evaluated after 8 hours treatment in the control group and after 12 hours in the ultrafiltration group. Following parameters were compared between the two groups: body weight, dyspnea score and 6 minutes walking distance as well as blood pressure, heart rate, Na⁺ , K⁺ , Cl^-, pH, HCO₃^-, Hb, PLT, Cr, BUN levels. Results: (1)Two patients died during run-in process and eventually 132 cases were chosen for final analysis (65 cases in control group and 67 cases in the ultrafiltration group). Gender, age, type of heart failure, dyspnea score, body weight at baseline were similar between the two groups. (2)Post therapy, patients′ body weight decreased obviously, while dyspnea score and 6 minutes walking distance increased significantly in the ultrafiltration group compared to baseline(all P<0.05), and the improvement was significantly greater compared to control group(all P<0.05). (3)The safety index comparison of two groups: blood pressure, heart rate, Na⁺ , K⁺ , Cl^-, pH, HCO₃^-, Hb, PLT, Cr, and BUN were similar between the two groups at baseline and post therapy. Conclusion Ultrafiltration therapy is safe and effective to treat patients with heart failure.

Objective To evaluate the efficacy and safety of a new ultrafiltration device for treating refractory heart failure patients.Methods A total of 52 patients (37 male,age 29-85 (33 ± 44) years)with refractory heart failure were treated using a new ultrafiltration device (FQ-16).Body weight,dyspnea score,oxygen saturation (SatO2),left ventricular ejection fraction (LVEF),BUN,creatinine,electrolytes and blood gas analysis were assessed before and after the treatment.Hypotension event and other main adverse events were recorded.Results Ultrafiltration duration ranged between 8-22 hours.Total ultrafiltration volume was (4 489 ± 1 548) ml.Compared with baseline,patients' body weight decreased from (75.3 ± 8.74) kg to (69.8 ± 8.39) kg (P ＜ 0.01),dyspnea score improved from 2.47 ± 1.55 to 12.87±3.61 (P＜0.01) and SatO2 increased from 91.0 ±6.01 to 96.4 ±2.52 (P ＜0.01) and LVEF increased from (30.0 ± 4.1) ％ to (36.0 ± 4.3) ％ (P ＜ 0.01) after ultrafiltration.Blood creatinine,BUN,electrolytes and blood gas analysis values were similar at baseline and post ultrafiltration.No hypotension event and other main adverse events occurred during the ultrafiltration treatment.Conclusions The novel ultrafiltration device adequately relieved hypervolemia and dyspnea in patients with refractory heart failure and the treatment process is safe in this patient cohort.