Acute pancreatitis (AP) is a life-threatening gastrointestinal disorder for which no effective pharmacological treatments are currently available. One of the pharmacological targets that merits further research is the neurokinin 1 receptor (NK1R), which is found on pancreatic acinar cells and responds to the neuropeptide substance P (SP) that participates in AP. Although a few studies have stated the involvement of SP/NK1R in neurogenic inflammation in AP development, the regulatory mechanism remains unclear. In this study, we found that following activation of NK1R by SP, β-arrestin1, a scaffold protein of NK1R, down-regulated transcription of Adss, Adsl, and Ampd in the purine nucleotide cycle, thereby inhibiting mitochondrial function through fumarate depletion. Interestingly, we identified magnolol as a new and natural NK1R inhibitor with a non-nitrogenous biphenyl core structure. It exhibited a beneficial effect on AP by restoring purine nucleotide cycle metabolic enzymes and fumarate levels. Our study not only provides new therapeutic strategies, leading compounds, and drug translation possibilities for AP, but also provides important clues for the study of downstream mechanisms driven by SP in other diseases.

Glioma is a common primary intracra-nial tumor.Malignant glioma has a high mortality rate and an inferior prognosis.Despite various ther-apeutic interventions,the overall survival rate is still meager.Sesquiterpene lactone is a kind of natu-ral product containing α-methylene-γ-lactone,which has strong anti-tumor activity.In recent years,there have been many reports on the anti-gli-oma effect of sesquiterpene lactone compounds,such as ACT001,which is a structural modification of sesquiterpene lactone(Parthenolide)and has en-tered the clinical trial stage as a potential antican-cer drug.This paper reviews the activity and mecha-nism of sesquiterpene lactones with anti-glioma ef-fects,which have been studied in recent.years.

Bronchopulmonary dysplasia is the most common chronic lung disease in very preterm infants.Some severe bronchopulmonary dysplasia is often combined with pulmonary hypertension，characterized by diffuse alveolar damage and abnormal pulmonary vascular remodeling，followed by right heart failure due to increased pulmonary vascular resistance.It seriously affects the physical and neurological development of preterm infants.Pulmonary vasodilator drugs can reduce pulmonary artery pressure through nitric oxide pathway，endothelin pathway and prostaglandin pathway.This review summarized the pulmonary vasodilator drugs in the treatment of pulmonary hypertension associated with bronchopulmonary dysplasia.

As the first marketed epidermal growth factor receptor tyrosine kinase inhibitor, gefitinib plays an important role in the targeted therapy of malignant tumors such as non-small cell lung cancer, but this drug can cause serious adverse effects such as liver toxicity. If the reaction occurs, the drug must be stopped for liver protection treatment, which greatly affects the treatment process of cancer. However, the mechanism of gefitinib-induced hepatotoxicity is still unclear, and clinical treatment measures are very limited. This article aims to review the molecular mechanism of gefitinib-induced hepatotoxicity and the commonly used clinical therapeutic drugs, so as to provide scientific basis for clinical prevention and rational drug use.

[Abstract] Objective: To explore the expression patterns of melanoma lineage antigens and nuclear antigen Ki-67 and their correlations with survival in melanoma patients. Methods: A retrospective analysis was conducted to analyze the pathological data of melanoma patients treated at the Department of Melanoma, Peking University Cancer Hospital from February 2008 to August 2020, mainly including the expression patterns of melanoma lineage antigens (S-100, HMB-45, Melan-A) and Ki-67, demographics, clinical features and survival. The correlation between expression patterns of melanoma lineage antigens, Ki-67 and melanoma-specific survival (MSS) was analyzed. Results: In total, 603 patients were included in this study. The median follow-up time was 47.4 months. The positive rates of S-100, HMB, and Melan-A were 92.8%, 92.1% and 90.0%, respectively. The percentages of patients with melanoma lineage antigen scores (S-100, HMB-45 and Melan-A was scored each, as 1 when positive and 0 when negative) of 0, 1, 2, and 3 were 0.5%, 5.0%, 15.6%, and 78.8%, respectively. The percentages of patients with Ki-67 scores of 0, 1, 2, and 3 were 43.0%, 36.3%, 16.3%, and 4.5%, respectively. Ki-67 was highly expressed in mucosal and progressive melanomas. In a multivariate analysis, Ki-67 expression was an independent prognostic factor for poorer MSS (HR=1.506, 95%CI: 1.248-1.818, P<0.001) as the incidence of MSS event increased by 50% per 25% increase in Ki-67 expression, whereas there was no statistical correlation between melanoma lineage antigen expression and MSS (HR=0.991, 95%CI: 0.759-1.293, P=0.94). Conclusion: High expressions melanoma lineage antigens are ubiquitous in melanoma tissues, and Ki-67 is an independent prognostic factor for MSS.

[摘 要] 目的：本研究旨在评估白蛋白紫杉醇+卡铂联合抗血管生成药物（nab-paclitaxel, carboplatin, antiangiogenic drug, NCA）方案用于既往治疗失败的晚期黑色素瘤患者的疗效和安全性。方法：收集2012年4月1日至2019年5月31日在北京大学肿瘤医院肾癌黑色素瘤科住院的黑色素瘤患者，回顾性分析NCA方案在既往治疗失败后的不可切除Ⅲ c期和Ⅳ期黑色素瘤患者中的疗效和安全性。主要终点指标为无进展生存期（PFS），次要指标为客观缓解率（ORR）、总生存期（OS）、疾病控制率（DCR）和不良反应。根据使用的抗血管药物分为恩度治疗组（n=73）和贝伐珠单抗治疗组（n=103），采用倾向性评分匹配以均衡不同抗血管生成药物组间基线变量的差异。结果：共计176例患者被纳入本项分析中。所有患者中位年龄51岁（范围为18~78岁）。Ⅳ期患者占97%，50%的患者LDH水平高于正常值，28%的患者存在肝转移。既往治疗线数占比分别为1线57%、2线33%、3~4线10%。所有患者的中位PFS为3.8个月（95%CI：3.0~4.6），中位OS为10.5个月（95%CI： 8.9~12.1）。2例患者获得完全缓解，9例患者获得部分缓解，全组的ORR为6%，DCR达70%。恩度治疗组和贝伐珠单抗治疗组的中位PFS分别为4.7个月（95%CI：3.5~5.9）和3.4个月（95%CI：3.0~4.6），两组中位OS分别为12.2个月（95% CI：11.1~13.2）和9.1个月（95%CI： 7.8~10.4）。对所有患者的年龄、性别、既往治疗线数和LDH水平进行倾向性评分匹配，贝伐珠单抗和恩度治疗组间PFS和OS差异无统计学意义。常见的不良反应包括脱发、周围神经病变、中性粒细胞减少、疲劳和恶心。26名（15%）患者由于不良反应停止了治疗。结论：白蛋白紫杉醇+卡铂联合抗血管生成药物对既往治疗失败的晚期黑色素瘤患者具有一定的疗效，不良反应可耐受。

Objective: To analyze the anesthetic effect of dexmedetomidine in laparoscopic D2 radical gastrectomy and its influence on hemodynamics, visual analogue scale (VAS) and Ramsay sedation score after operation. Methods: A total of 86 patients who received laparoscopic D2 radical gastrectomy under general intravenous anesthesia in Shanxi Provincial Cancer Hospital from March 2017 to June 2017 were enrolled, and all the patients were divided into two groups by using random number table method. The observation group (43 cases) was intravenously injected with dexmedetomidine (0.6 μg/kg) before induction of general anesthesia, and the dose was changed to 0.4 μg/kg after 15 min with drug withdrawal till 30 minutes before surgery, the control group (43 cases) was given an equal volume of 0.9% normal saline. The mean arterial pressure (MAP) and heart rate change before anesthetic induction (T₁), tracheal intubation time (T₂), after intubation (T₃), section time (T₄) and the immediate time after intubation (T₅) were compared between the two groups. The VAS and Ramsay scores at 1 h and 4 h after surgery and the intraoperative doses of anesthesia maintenance drugs were also compared between the two groups. Results: The heart rate and MAP of the observation group were lower than those of the control group at the time of T₁, T₃-T₅, the differences were statistically significant (all P < 0.05). The VAS and Ramsay scores of the observation group were better than those of the control group at 1 h and 4 h after operation, and the differences were statistically significant (all P < 0.05). The intraoperative doses of propofol and remifentanil in the observation group were (964±251) mg and (3.1±0.8) mg, respectively, which were less than those in the control group [(1 485±425) mg and (4.8±0.8) mg], the differences were statistically significant (t = 9.913, P < 0.01; t = 9.834, P < 0.01). Conclusion Dexmedetomidine can reduce the stress response of patients with laparoscopic D2 radical anesthesia, enhance the sedative effect, and reduce the dosage of propofol and remifentanil, therefore, it has high clinical application value.

Objective To study the epidemiologic characteristics of influenza in Gansu province of China and to optimize the related vaccination program.Methods Weekly influenza surveillance data from the first week of 2010 to the fortieth week of 2016 were collected,in Gansu province.x2 test was used to compare the differences of nucleic acid positive rate and the virus types in the four seasons.Time series seasonal decomposition (TSSD) was used to explore seasonal patterns and characteristics of influenza epidemics in Gansu.Results 59 791 specimens were tested,with 8 501 positive for influenza virus and positive rates as 14.22％.Types A(H1N1)pdm09,A(H3N2) and type B were accounted for 98.76％ of all the positive specimens.Proportions of the positive rate of influenza virus appeared in spring,summer,autumn and winter were 15.12％,0.98％,4.02％ and 24.26％ respectively.The predominant type of virus in autumn and winter was A(H3N2),with B mainly in spring.Influenza in Gansu province showed typical single-peak type distribution,with epidemic peak appeared from December to next January.The type A(H3N2) related peak appeared the earliest,followed by A(H1N1)pdm09,with type B the latest.Conclusions Peaks and the duration of influenza seasonal epidemics were related to the types of dominant strains.Annual influenza vaccination campaigns should start in October,to provide effective protection during the epidemic period.

Objective To understand the dominant pathogens of febrile respiratory syndrome (FRS) patients in Gansu province and to establish the Bayes discriminant function in order to identify the patients infected with the dominant pathogens.Methods FRS patients were collected in various sentinel hospitals of Gansu province from 2009 to 2015 and the dominant pathogens were determined by describing the composition of pathogenic profile.Significant clinical variables were selected by stepwise discriminant analysis to establish the Bayes discriminant function.Results In the detection of pathogens for FRS,both influenza virus and rhinovirus showed higher positive rates than those caused by other viruses (13.79％,8.63％),that accounting for 54.38％,13.73％ of total viral positive patients.Most frequently detected bacteria would include Streptococcus pneumoniae,and haemophilus influenza (44.41％,18.07％) that accounting for 66.21％ and 24.55％ among the bacterial positive patients.The original-validated rate of discriminant function,established by 11 clinical variables,was 73.1％,with the cross-validated rate as 70.6％.Conclusion Influenza virus,Rhinovirus,Streptococcus pneumoniae and Haemophilus influenzae were the dominant pathogens of FRS in Gansu province.Results from the Bayes discriminant analysis showed both higher accuracy in the classification of dominant pathogens,and applicative value for FRS.

Objective To investigate the expression of CXC chemokine receptor 1 (CXCR1) and CXC chemokine receptor 2 (CXCR2) in triplenegative breast cancer (TNBC) and its significance.Methods The EnVision immunohistochemistry system was used to detect the expression of CXCR1 and CXCR2 in 28 specimens from normal tissues adjacent to breast cancer,30 specimens of invasive ductal carcinoma not otherwise specified (IDC-NOS),and 34 TNBC specimens.The relationship between the expression of CXCR1 and CXCR2,and clinical pathological features was analyzed.Results In the adjacent normal tissues of breast cancer,the positive expression rates of CXCR 1 and CXCR2 were 89.3％ and 92.9％,respectively;CXCR1 and CXCR2 expression displayed no significant association with clinicopathological parameters such as age,tumor size,or Scarff-Bloom-Richardson (SBR) score.The positive expression rates of CXCR1 and CXCR2 were 63.3％ and 60.0％,respectively,in the IDC-NOS samples and 23.5％ and 35.3％,respectively,in the TNBC samples.There was a positive correlation between CXCR1 and CXCR2 expression in the TNBC samples (r =0.606,P ＜ 0.001).Conclusion Correlation of CXCR1 and CXCR2 expression with sample type was strong in adjacent normal tissues,moderate in IDC-NOS samples,and low in TNBC samples.CXCR1 expression was positively correlated with CXCR2 expression in all sample types.The expression of CXCR1 or CXCR2 was closely related to the development and promotion of TNBC.