OBJECTIVE To explore the effects and potential mechanism of evodiamine on inflammatory response and apoptosis of epithelial cells in asthma model rats. METHODS SD rats were separated into control group， model group， evodiamine low-dose group （10 mg/kg）， evodiamine high-dose group （20 mg/kg）， dexamethasone group （positive control， 0.5 mg/kg）， epidermal growth factor （EGF） group [mitogen-activated protein kinase （MAPK） activator， 10 μg]， evodiamine high-dose+EGF group （20 mg/kg evodiamine+10 μg EGF）， with 10 rats in each group. Except for the control group， the other groups were sensitized by 3-point injection of 10% ovalbumin（OVA）-aluminium hydroxide mixture and stimulated by inhalation of 2%OVA nebulized liquid to establish an asthma model. The count of inflammatory cells （macrophages and lymphocytes） in bronchoalveolar lavage fluid （BALF） was detected in each group； pathological changes of lung tissue in rats were observed； the apoptosis of airway epithelial cells， the levels of serum inflammatory factors [tumor necrosis factor-α， interleukin-6 （IL-6） and IL-4]， the expressions of pathway-related proteins p38 MAPK， phosphorylated p38 MAPK （p-p38 MAPK）， signal transduction and transcription activating factor 1 （STAT1）] and apoptosis-related proteins [B cell lymphoma-2 （Bcl-2） and Bcl-2 associated X protein （Bax）] were all detected in lung tissue. RESULTS Compared with the control group， bronchial mucosal edema， thickening of alveolar septa and extensive infiltration of inflammatory cells were observed in the lung tissue of rats in the model group； the number of inflammatory cells， apoptosis rate of airway epithelial cells， the levels of inflammatory factors， p-38 MAPK/p-38 MAPK， and the protein expressions of Bax and STAT1 were increased significantly； the expressions of Bcl-2 protein and Bcl-2/Bax were reduced significantly （P＜0.05）. Compared with the model group， the pathological changes in lung tissues were alleviated to varying degrees in evodiamine low-dose and high-dose groups， and dexamethasone groups， and the above indicators were significantly reversed. However， the change trends of corresponding indicators in the EGF group were opposite to the above （P＜0.05）. EGF could significantly attenuate the effect of high-dose evodiamine on inflammatory response in asthmatic rats （P＜0.05）. CONCLUSIONS Evodiamine can relieve inflammatory reactions and inhibit the apoptosis of airway epithelial cells in asthmatic rats， the mechanism of which may be associated with inhibiting p38 MAPK/STAT1 signaling pathway.

OBJECTIVE To explore the effects and potential mechanism of evodiamine on inflammatory response and apoptosis of epithelial cells in asthma model rats. METHODS SD rats were separated into control group， model group， evodiamine low-dose group （10 mg/kg）， evodiamine high-dose group （20 mg/kg）， dexamethasone group （positive control， 0.5 mg/kg）， epidermal growth factor （EGF） group [mitogen-activated protein kinase （MAPK） activator， 10 μg]， evodiamine high-dose+EGF group （20 mg/kg evodiamine+10 μg EGF）， with 10 rats in each group. Except for the control group， the other groups were sensitized by 3-point injection of 10% ovalbumin（OVA）-aluminium hydroxide mixture and stimulated by inhalation of 2%OVA nebulized liquid to establish an asthma model. The count of inflammatory cells （macrophages and lymphocytes） in bronchoalveolar lavage fluid （BALF） was detected in each group； pathological changes of lung tissue in rats were observed； the apoptosis of airway epithelial cells， the levels of serum inflammatory factors [tumor necrosis factor-α， interleukin-6 （IL-6） and IL-4]， the expressions of pathway-related proteins p38 MAPK， phosphorylated p38 MAPK （p-p38 MAPK）， signal transduction and transcription activating factor 1 （STAT1）] and apoptosis-related proteins [B cell lymphoma-2 （Bcl-2） and Bcl-2 associated X protein （Bax）] were all detected in lung tissue. RESULTS Compared with the control group， bronchial mucosal edema， thickening of alveolar septa and extensive infiltration of inflammatory cells were observed in the lung tissue of rats in the model group； the number of inflammatory cells， apoptosis rate of airway epithelial cells， the levels of inflammatory factors， p-38 MAPK/p-38 MAPK， and the protein expressions of Bax and STAT1 were increased significantly； the expressions of Bcl-2 protein and Bcl-2/Bax were reduced significantly （P＜0.05）. Compared with the model group， the pathological changes in lung tissues were alleviated to varying degrees in evodiamine low-dose and high-dose groups， and dexamethasone groups， and the above indicators were significantly reversed. However， the change trends of corresponding indicators in the EGF group were opposite to the above （P＜0.05）. EGF could significantly attenuate the effect of high-dose evodiamine on inflammatory response in asthmatic rats （P＜0.05）. CONCLUSIONS Evodiamine can relieve inflammatory reactions and inhibit the apoptosis of airway epithelial cells in asthmatic rats， the mechanism of which may be associated with inhibiting p38 MAPK/STAT1 signaling pathway.

Objective:To construct an evidence-based prediction model for early recurrence after surgery of hepatocellular carcinoma (HCC) based on Meta-analysis and to do external validation study.Methods:The literatures in Chinese National Knowledge Infrastructure, Wanfang, VIP, Chinese Science Citation Database (CSCD), Chinese Social Science Citation System (CCSCI), PubMed, Web of Science and IEEE databases between January 2019 and December 2023 were searched based on the subject words. According to the inclusion and exclusion criteria, 9 literatures were included to screen the risk factors affecting the early recurrence of HCC. When the same risk factor was found in ≥5 included literatures, Meta-analysis was performed by using Review Manager 5.4.1 software. External validation data were collected from 401 patients with primary HCC who underwent surgery in Liaoning Cancer Hospital between March 2014 and March 2017. The patients were divided into early recurrence group (176 cases) and early non-recurrence group (225 cases) according to whether they relapsed 2 years after surgery. The OR values of all risk factors obtained in the Meta-analysis were converted into modeling, and postoperative early recurrence rate of HCC in the Meta-analysis was used to calculate β 0, and finally the logistic model was obtained. The OR value was incorporated into the logit (P) model, and the morbidity (P) of the external validation data was calculated. Taking the recurrence 2 years after surgery or not as the dependent variable and P as the independent variable, the receiver operating characteristic (ROC) curve was drawn to calculate the area under the curve (AUC). Results:A total of 8 risk factors for early HCC recurrence were screened out from 9 literatures (x 1: alpha-fetoprotein ≥ 400 ng/ml; x 2: tumor number ≥ 2; x 3: the longest tumor diameter ≥ 5 cm; x 4: Barcelona staging B-C; x 5: microvascular invasion; x 6: moderate to low differentiation; x 7: incomplete capsule; x 8: nonanatomic hepatectomy). The Meta-analysis included 1 757 HCC cases, with 960 postoperative early recurrences and an early recurrence rate of 45.36%, finally the β 0 value was -0.201. The predictive model for 2-year recurrence of HCC was constructed and calculated as logit (P) = -0.201+0.835x 1+0.905x 2+0.783x 3+1.008x 4+0.765x 5+0.831x 6+1.533x 7+0.940x 8. Analysis of variance by external validation data showed that the differences in ascites, alpha-fetoprotein, tumor number, tumor diameter, Barcelona staging, microvascular invasion, tumor differentiation degree, capsule invasion, resection type, and systemic inflammation index were statistically significant between early recurrence group and early non-recurrence group (all P < 0.05). ROC curve analysis showed that AUC of postoperative early recurrence of HCC predicted by the model was 0.718, (95% CI: 0.689-0.753), the optimal cut-off value was 3.11, the Yoden index was 0.288, the sensitivity was 69.32%, and the specificity was 69.56%. Conclusions:The evidence-based prediction model constructed based on Meta-analysis for postoperative early recurrence of HCC has a high predictive value. However, further verification and optimization with big data is still needed.

Objective:To investigate the impacts of Schisandrin B(Sch B)on airway inflammation and airway remodeling in asthmatic rats by regulating Noxa/Heat shock protein 27(Hsp27)/nuclear factor-κB(NF-κB)signaling pathway.Methods:SD male rats were randomly separated into control group(normal feeding),asthma group,Sch B-L group(40 mg/kg),Sch B-H group(80 mg/kg),positive control group(0.5 mg/kg dexamethasone),Vector group(tail vein injection of empty plasmid+80 mg/kg Sch B),Noxa group(tail vein injection of Noxa overexpression plasmid+80 mg/kg Sch B),with 6 rats in each group.Except the control group,6 groups of rats were sensitized and stimulated with ovalbumin to establish asthma rat model,and were given drug intervention,once a day for four weeks.RT-qPCR was applied to measure the expression of Noxa in lung tissue;differential white blood cell counts in bronchoalveolar lavage fluid(BALF)were performed;ELISA was applied to measure the levels of IL-4,INF-α,IL-13 and IL-5 in rat serum;HE staining was applied to observe the histopathology of lung tissue of rats in each group;expression of Noxa protein and phosphorylation levels of Hsp27 and NF-κB in lung tissue were detected by Western blot.Results:Compared with the Vector group,the expression lev-el of Noxa in the left lung tissue of the Noxa group was obviously increased;compared with the control group,the right lung tissue structure of the rats in the asthma group was obviously damaged,the tracheal tube was obviously narrowed,the interstitium was mas-sively inflammatory infiltration,the thickness of the bronchial smooth muscle,the thickness of the basement membrane and the cir-cumference of the basement membrane were obviously increased,and the cells in the BALF were obviously increased,the total num-ber,eosinophils,neutrophils,and lymphocytes were obviously increased,and macrophages were obviously decreased,the levels of serum TNF-α,IL-4,IL-5 and IL-13 were obviously increased,the expression levels of Noxa,p-Hsp27/Hsp27,p-NF-κB p65/NF-κB p65 in the left lung tissue were obviously increased(P<0.05);compared with the asthma group,the duct stenosis in the right lung tis-sue of the Sch B-L group,the Sch B-H group and the positive control group were obviously improved,the inflammatory infiltration was reduced,the thickness of the bronchial smooth muscle,the thickness of the basement membrane and the circumference of the base-ment membrane were obviously reduced,and the cells in the BALF were obviously reduced,the total number,eosinophils,neutro-phils,and lymphocytes were obviously decreased,and macrophages were obviously increased,the levels of serum TNF-α,IL-4,IL-5 and IL-13 were obviously decreased,the expression levels of Noxa,p-Hsp27/Hsp27,p-NF-κB p65/NF-κB p65 in the left lung tissue were obviously decreased and was dependent on dose(P<0.05);overexpression of Noxa attenuated the ameliorating effects of Sch B on airway inflammation and airway remodeling in asthmatic rats.Conclusion:Sch B can effectively ameliorate airway inflammation and airway remodeling in asthmatic rats by regulating Noxa/Hsp27/NF-κB signaling pathway.

Objective To retrospectively analyze the efficacy and safety of abatacept(ABA)in anti citrullinated peptide antibody(ACPA)positive rheumatoid arthritis(RA).Methods Clinical data from ACPA positive RA patients who visited the Department of Rheumatology and Immunology at the Second Hospital of Hebei Medical University from May 2020 to January 2023 and were treated with ABA were retrospectively collected and analyzed,to evaluate the efficacy and safety of ABA at 12 weeks and 24 weeks of treatment.Efficacy evaluation measures included RA disease activity score-28(DAS-28),clinical disease activity index(CDAI),and remission criteria of RA of American College of Rheumatology(ACR).Results A total of 35 ACPA-positive RA patients were included in the final analysis.The DAS-28,CDAI,ACR20,ACR50,and ACR70 remission rates at 12 weeks after treatment were 34.29%,31.43%,60.00%,28.57%,and 14.29%,respectively;the DAS-28,CDAI,ACR20,ACR50,and ACR70 remission rates at 24 weeks after treatment were 74.29%,82.86%,85.71%,54.29%,and 31.43%,respectively;in addition,the remission rate at 24 weeks was significantly higher than that at 12 weeks(P﹤0.05).Among the 35 patients included in the analysis,4 patients experienced respiratory tract infections,3 patients experienced transient creatinine elevation,and 4 patients experienced elevated blood uric acid.Conclusion In the real world,ABA's clinical remission rate is consistent with expectations,and clinical combination drug regimens are flexible and diverse,with high drug safety.

With the progress of society and the continuous improvement of people′s living standards in China, the public′s demand for medical services is becoming increasingly diversified. How to move hospital services forward and improve medical services centered on patients has become a key consideration for hospitals to enhance patients′ sense of medical satisfaction. A certain hospital has established a one-stop patient service hotline, integrating functions such as number inquiry, medical consultation, appointment registration, appointment examination, praise and suggestions, complaint follow-up, etc., injecting a complaint handling management mode, and responding to and solving patient feedback problems in a timely manner. Since the launch of the patient service hotline, it has effectively solved the problems that patients encountered during their visits, effectively reduced the hospital′s complaint rate, and initially formed a service closed-loop management. From March to October 2023, the demand ratio of the 12345 hotline in the hospital has continuously decreased, and was significantly lower than the average level of 22 municipal hospitals in Beijing. In the future, we should further improve the communication skills between doctors and patients, focus on managing appeals and services, and continue to strengthen proactive governance.

H 1-antihistamines are widely used in the treatment of various allergic diseases, but there are still many challenges in the safe and rational use of H 1-antihistamines in pediatrics, and there is a lack of guidance on the prescription review of H 1-antihistamines for children.In this paper, suggestions are put forward from the indications, dosage, route of administration, pathophysiological characteristics of children with individual difference and drug interactions, so as to provide reference for clinicians and pharmacists.

Aristolochic acids (AAs) have long been considered as a potent carcinogen due to its nephrotoxicity. Aristolochic acid I (AAI) reacts with DNA to form covalent aristolactam (AL)-DNA adducts, leading to subsequent A to T transversion mutation, commonly referred as AA mutational signature. Previous research inferred that AAs were widely implicated in liver cancer throughout Asia. In this study, we explored whether AAs exposure was the main cause of liver cancer in the context of HBV infection in mainland China. Totally 1256 liver cancer samples were randomly retrieved from 3 medical centers and a refined bioanalytical method was used to detect AAI-DNA adducts. 5.10% of these samples could be identified as AAI positive exposure. Whole genome sequencing suggested 8.41% of 107 liver cancer patients exhibited the dominant AA mutational signature, indicating a relatively low overall AAI exposure rate. In animal models, long-term administration of AAI barely increased liver tumorigenesis in adult mice, opposite from its tumor-inducing role when subjected to infant mice. Furthermore, AAI induced dose-dependent accumulation of AA-DNA adduct in target organs in adult mice, with the most detected in kidney instead of liver. Taken together, our data indicate that AA exposure was not the major threat of liver cancer in adulthood.

Objective : To assess the safety and feasibility of incision in the retroauricular sulcus for removal of benign tumors in the lower pole of the parotid gland and to provide some ideas for aesthetic consideration of parotidectomy. Methods: In total, 18 cases with benign tumors of the lower pole regions of the parotid gland were included in this study, including 9 pleomorphic adenomas, 2 myoepitheliomas, 5 Warthin tumors, 1 basal cell adenoma and 1 oncocytoma. Three months after the operation, facial paralysis and salivary fistula were assessed. A visual analog scale was used to score the cosmetic satisfaction of the surgical incision. Tumor recurrence was followed up 6 ~ 12 months after operation. Results: In 18 patients with benign tumors the lower pole regions of the parotid gland, the tumor diameter ranges from 1.0 to 3.1 cm, with an average value of 2.5 cm. All patients experienced successful complete removal of the parotid mass with the minimally invasive retroauricular approach, and all wounds healed in one stage after operation. No serious complications, such as permanent facial paralysis and tumor recurrence, occurred 3 months after the operation. The patients were satisfied with the appearance of the surgical incision (aesthetic score 9.3 ± 0.4), achieving the expected aesthetic effect. Conclusion This approach is feasible and safe for most small benign parotid tumors located in the lower pole region of the parotid gland and in the posterior region of the jaw. The scar is located in the retroauricular sulcus, which significantly meets the aesthetic needs of the concealed incision for patients.

Objective:To explore the correlation between the level of heart rate deceleration (DC), serum homocysteine(Hcy), the scope and extent of coronary artery lesion in coronary heart disease patients with hypertension.Methods:From January 2019 to October 2019, 103 coronary heart disease patients with hypertension who were diagnosed and hospitalized in cardiovascular department of Binzhou Central Hospital were selected as coronary heart disease(CHD) group, and 52 patients with simple hypertension were selected as control group.The serum Hcy levels of the two groups were measured and analyzed.The DC value and the difference of the two groups were analyzed.The degree of coronary artery lesion was evaluated by the number of coronary artery lesion and Gensini score.The relationship between DC, Hcy and the degree of coronary artery lesion was analyzed.Results:Compared with the control group, the DC value of CHD group was significantly lower [(6.02±1.97)ms vs.(4.97±1.59)ms, t=-3.989, P<0.05], and the serum Hcy level was increased [(11.46±4.38)μmol/L vs.(16.79±6.31)μmol/L, t=4.260, P<0.05]. In the CHD group, the DC values and Gensini scores of the patients with single vessel lesion, double vessel lesions and three vessel lesions were (5.52±1.34)ms, (5.06±1.29)ms, (4.39±1.19)ms, (21.35±17.10)points, (26.93±18.18)points, (49.39±30.14)points, respectively.The DC value of patients with three vessel lesions was lower than that of patients with single vessel lesion( F=7.349, P<0.05), and the Gensini score was higher( F=13.487, P<0.05). There were no statistically significant differences in DC value and Gensini score between patients with three vessel lesions and those with two vessel lesions and those with single vessel lesion( P>0.05). The serum Hcy levels of patients with single, double and three vessel lesions were (14.67±5.97)μmol/L, (15.85±6.29)μmol/L and (16.97±7.13)μmol/L, respectively.The difference among the three groups was statistically significant ( F=12.427, P<0.05). There was a negative correlation between DC and Gensini score( r=-0.310, P<0.05), and a positive correlation between serum Hcy and Gensini score( r=0.369, P<0.05). Conclusion:The DC value and Hcy level in coronary heart disease patients with hypertension are significantly decreased, which are closely related to the degree of coronary artery lesion.