目的 研究靶向NKG2A抑制剂抗头颈部鳞状细胞癌（HNSCC）的作用。方法 应用GEO和TCGA数据库分析NKG2A及其配体HLA-E单细胞表达情况、与患者预后以及免疫微环境的相关性。构建HNSCC皮下抑制瘤模型,流式细胞技术检测化学治疗（化疗）对免疫检测点NKG2A表达的影响。动物实验验证NKG2A抑制剂以及NKG2A抑制剂联合多西他赛化疗的抗肿瘤作用。结果 NKG2A（KLRC1）主要表达在NK细胞,少量表达在T淋巴细胞。HNSCC肿瘤高表达NKG2A/HLA-E（P<0.01）,与患者不良预后密切相关;肿瘤微环境中NKG2A/HLA-E与多个免疫细胞浸润以及免疫检测点表达密切相关（P<0.01）。动物实验显示化疗能上调T、B淋巴细胞表达免疫检查点NKG2A的表达水平（P<0.01）;化疗的基础上联合NKG2A抑制剂能更有效地介导抗肿瘤作用（P=0.013）。结论 化疗基础上联合NKG2A抑制剂能更有效地介导抗肿瘤作用,为探索HNSCC临床新策略提供实验和理论基础。

Objective To investigate the anti-tumor effects of NKG2A inhibitor on head and neck squamous cell carcinoma（HNSCC）．Methods The single-cell expression of NKG2A ,its ligand HLA-E and their correlations with patient prognosis and immune microenvironment were analyzed in GEO and TCGA databases．The subcutaneous tumor model of HNSCC was constructed,and the effects of chemotherapy on the expression of NKG2A on T and B lymphocytes were detected by flow cytometry．Animal experiments were used to confirmed the anti-tumor effects of NKG2A inhibitor and NKG2A inhibitors combined with docetaxel．Results NKG2A（KLRC1）was mainly expressed in NK cells,and a small amount was expressed in T lymphocytes．The high expression of NKG2A/HLA-E in HNSCC tumors（P<0.01）were closely related to poor prognosis．NKG2A/HLA-E in tumor microenvironment were closely related to the infiltration of multiple immune cells and the expression of immune checkpoints（P<0.01）．Animal experiments showed that chemotherapy could up-regulate the expression of NKG2A in T and B lymphocytes（P<0.01）．Chemotherapy in combination with NKG2A inhibitor could mediate more effective antitumor effects in HNSCC（P=0.013）．Conclusions Combined with NKG2A inhibitor on the basis of chemotherapy can mediate more effective anti-tumor effects,and this study may provide experimental and theoretical basis for exploring new clinical strategies of HNSCC．

目的 评价不同间变性淋巴瘤激酶（ALK）抑制剂联合安罗替尼治疗非小细胞肺癌（NSCLC）的疗效。方法 收集ALK突变阳性NSCLC患者的临床资料,筛选服用ALK抑制剂疗效不佳再加用安罗替尼的病例。根据不同的用药方案分为阿来替尼+安罗替尼,塞瑞替尼+安罗替尼和克唑替尼+安罗替尼三个组别。记录患者联合用药前最近一次的影像学检查结果,并以此为基线按Recist1.1评价疗效,以病情进展、患者死亡、停药、改变治疗方案为终点计算各组患者的无事件生存期（EFS）,收集肿瘤标志物、血常规和肝功、心功能、肾功能生化检测等指标数据,统计分析患者联合用药前后各项指标的变化。结果 经筛选,共纳入49例患者的临床数据。阿来替尼+安罗替尼组有23例,疾病控制率（DCR）为86.96%;平均EFS为（10.8±3.6）个月,中位EFS为8.3个月;塞瑞替尼+安罗替尼组有14例,DCR为71.43%;平均EFS为（6.5±2.9）个月,中位EFS为5.6个月;克唑替尼+安罗替尼组有12列,DCR为66.67%;平均EFS为（7.7±3.2）个月,中位EFS为7.2个月。阿来替尼+安罗替尼组的平均EFS长于另外两组（P<0.05）。各研究组肿瘤标志物仅有CyFra21-1在克唑替尼+安罗替尼组在联合用药后升高（P<0.05）,生化检测和血常规指标在用药前后差异无统计学意义（P>0.05）。结论 ALK抑制剂与安罗替尼联用,疗效最好为阿来替尼,其次为塞瑞替尼,最后为克唑替尼。三种ALK抑制剂与安罗替尼联用后,均未导致心、肝、肾功能和血细胞损害。

Objective To evaluate the efficacy of different anaplastic lymphoma kinase（ALK）inhibitors combined with anlotinib in the treatment of non-small cell lung cancer（NSCLC）. Methods Clinical data of drug resistant NSCLC patients with ALK positive mutation was collected who were treated with ALK inhibitors and anlotinib synchronously．According to different regimens,three groups were set,alectinib+anlotinib,ceritinib+anlotinib,and crizotinib+anlotinib．The latest imageological examination results of the patient before the synchronous therapy was set as the baseline to evaluate the therapeutic effect according to Recist1.1．The event free survival（EFS）of each group was calculated with disease progression,patient death,treatment discontinuation and changing regimen as endpoints．Data of tumor markers,hematology test,liver function,cardiac function,renal function biochemical examination was collected and analyzed statistically before and after the combination therapy,with P<0.05 as the statistically significant difference. Results After screening,clinical data of 49 patients were collected．Twenty-three patients in the alectinib+anlotinib group,with a disease control rate（DCR） of 86.96%;mean EFS was（10.8±3.6）months,median EFS of 8.3 months;14 patients in the ceritinib+anlotinib group,with a DCR of 71.43%,mean EFS was（6.5±2.9）months,median EFS was 5.6 months;12 patients in the crizotinib+anlotinib group,with a DCR of 66.67%,mean EFS was（7.7±3.2）months,median EFS was 7.2 months．EFS of alectinib+anlotinib group was longer significantly than the other two groups（P<0.05）．Only CyFra21-1,increased significantly after the combination of crizotinib and anlotinib（P<0.05）．No statistically significant difference in biochemical test and hematology test before and after the treatment（P>0.05）． Conclusions The therapeutic effect of ALK inhibitors with anlotinib was ordered,alectinib being the most effective,followed by ceritinib and finally crizotinib．The combination of ALK inhibitors with anlotinib did not cause any abnormal results in the examination of heart,liver,kidney and blood cells．

目的 探讨表皮生长因子受体酪氨酸酶抑制剂（EGFR-TKIs）一线治疗耐药后,二线化学治疗（化疗）联合程序性死亡蛋白1及其配体（PD-1/L1）免疫检查点抑制剂方案对晚期非小细胞肺癌（NSCLC）的疗效。方法 选取2018年 6月—2022年10月期间就诊于南通大学附属肿瘤医院院的80例有完整临床资料、应用EGFR-TKIs耐药后晚期NSCLC患者进行回顾性分析,依照不同治疗方式将患者分为观察组与对照组,均为40例。对照组一线EGFR-TKIs治疗耐药后进行二线化疗,观察组一线EGFR-TKIs治疗耐药后进行二线化疗联合PD-1/L1免疫检查点抑制剂治疗。对比两组临床疗效及无进展生存期（PFS）,化疗前后血清中人细胞角蛋白21-1片段（Cyfra21-1）、糖类抗原125（CA125）、碱性成纤维细胞生长因子（bFGF）、血管内皮生长因子（VEGF）水平变化,不良反应发生率及生存质量。结果 观察组客观缓解率与疾病控制率高于对照组（P<0.05）,对照组PFS为10（2.38,24.13）个月,观察组PFS为14（5.27~,5.27）个月,观察组高于对照组（χ²=4.536,P=0.041）;化疗后两组bFGF、VEGF,CA125、Cyfra21-1肿瘤标志物水平均比化疗前降低,且观察组[（17.85±3.32）ng/L、（310.51±88.37）ng/L、（51.62±13.66）U/mL、（10.26±3.37）ng/mL]低于对照组[（19.62±3.24）ng/L、（366.26±49.42）ng/L、（59.26±9.35）U/mL、（12.62±2.73）ng/mL],对比差异有统计学意义（t₁=2.413,P₁=0.018;t₂=3.482,P₂<0.001;t₃=2.919,P₃=0.005;t₄=3.442,P₄<0.001）;两组不良反应发生率对比差异无统计学意义（P>0.05）;化疗后两组世界卫生组织生存质量量表简表评分均升高,观察组[（98.62±8.24）、（101.53±12.62）、（95.28±11.15）、（97.79±10.47）分]高于对照组[（84.25±7.32）、（93.58±15.75）、（82.24±9.34）、（83.47±8.38）]分,对比差异有统计学意义（t₁=8.246,P₁<0.001;t₂=2.491,P₂=0.015;t₃=5.670,P₃<0.001;t₄=6.753,P₄<0.001）。结论 对EGFR-TKIs耐药后晚期非小细胞肺癌患者采取二线化疗联合PD-1/L1免疫检查点抑制剂可提升其临床疗效及生存期,改善血清相关肿瘤标志物表达水平,提升患者生存质量。

Objective To explore the therapeutic effect of second-line chemotherapy combined with PD-1/L1 immune checkpoint inhibitor regimen on advanced non-small cell lung cancer（NSCLC） after epidermal growth factor receptor-tyrosine kinase inhibitors（EGFR-TKIs）resistance in first-line chemotherapy．Methods Retrospectively selected 80 patients with advanced NSCLC EGFR TKIs resistance,who were admitted to the Affiliated Cancer Hospital of Nantong University from June 2018 to October 2022．Patients were divided into an observation group and a control group according to different treatment methods,with 40 cases in each group．The control group received second-line chemotherapy after first-line EGFR-TKIs therapy resistance,while the observation group received second-line chemotherapy and PD-1/L1 inhibitor after first-line EGFR-TKIs therapy reactions and quality of live．Clinical efficacy and PFS,changes in serum levels of human Cyfra21-1,CA125,bFGF,VEGF,incidence of adverse chemotherapy of two groups were compared．Results The ORR and DCR of the observation group were significantly higher than those of the control group（P<0.05）．The mean PFS of the control group was 10（2.38-24.13）months,while the mean PFS of the observation group was 14（5.27-35.27）months．The observation group was higher than the control group（χ²=4.536,P=0.041）．After chemotherapy,levels of bFGF,VEGF,CA125 and Cyfra21-1 tumor markers decreased in both groups,and the observation group [（17.85±3.32）ng/L,（310.51±88.37）ng/L,（51.62±13.66）U/mL,（10.26±3.37）ng/mL] was lower than the control group [（19.62±3.24）ng/L,（366.26±49.42）ng/L,（59.26±9.35）U/mL,（12.62±2.73）ng/mL],which showed statistically significant difference in the comparison（t₁=2.413,P₁=0.018;t₂=3.482,P₂<0.001;t₃=2.919,P₃=0.005;t₄=3.442,P₄<0.001）．There was no significant difference in the incidence of adverse reactions between the two groups（P>0.05）．After treatment,the WHO QOL-BREF scores increased in both patient groups and the observation group scores[（98.62±8.24）,（101.53±12.62）,（95.28±11.15）,（97.79±10.47）] were higher than the control group scores[（84.25±7.32）,（93.58±15.75）,（82.24±9.34）,（83.47±8.38）],which showed statistically significant difference．（t₁=8.246,P₁<0.001;t₂=2.491,P₂=0.015;t₃=5.670,P₃<0.001;t₄=6.753,P₄<0.001）．Conclusions The combination of second-line chemotherapy with PD-1/L1 immune checkpoint inhibitors can improve the clinical efficacy and survival of advanced NSCLC patients who are resistant to EGFR-TKIs,improve the expression levels of serum related tumor markers,and enhance the quality of life of patients．

蒜氨酸为大蒜氨基酸成分,对机体无毒副作用,在体内代谢酶作用下分解成大蒜素,具有多种药理作用和广阔的临床应用前景。本文就蒜氨酸的分离提取、制剂及生物活性研究现状进行综述,以供参考。

Alliin is an amino acid component of garlic, no toxic side effects to the body. It breaks down into allicin by metabolic enzymes in the body, has a variety of pharmacological effects and broad clinical application prospects. In this paper, the isolation, extraction, preparation and biological activity of alliin were reviewed for reference.

近年来,由于抗生素的不合理使用,导致新型耐药性细菌不断出现,严重危害人类健康,迫使我们急需发现新型抗菌药物来对抗耐药性细菌引起的感染。FtsZ蛋白是细菌分裂的必需蛋白,在细菌分裂增殖过程中起着关键作用。当FtsZ的功能受到抑制时,细菌的分裂增殖亦会被抑制,最终导致细菌死亡。FtsZ蛋白是目前热门的抗菌新靶点之一。本文回顾了FtsZ蛋白的生物学功能,总结了以FtsZ为靶标的新型抗菌分子的研究进展。

Antibiotic-resistant bacterial infection has become epidemic all over the world. To overcome the drug resistance problem, antibacterial agents targeting at new binding sites become critical. FtsZ, a bacterial cell division protein, has become a new attractive target for antibacterial agents’ discovery because it is the most important and conserved protein in bacterial cell division. Cell division will be inhibited when the functions of FtsZ were disturbed. In this article, the biological functions of FtsZ have been reviewed, and recent advances in discovery of FtsZ inhibitors were summarized.

目的 探讨组蛋白去乙酰化酶抑制剂曲古霉素对肝癌细胞增殖凋亡是否存在影响,及该抑制作用是否与自噬相关。方法 采用MTT法检测不同浓度曲古霉素作用于肝癌HepG2细胞24 h、48 h、72 h以后肝癌细胞的增殖能力;使用流式细胞术检测不同浓度曲古霉素对HepG2肝癌细胞周期及凋亡的影响;蛋白印迹法(Western blot, WB)检测不同浓度曲古霉素对肝癌HepG2细胞中Beclin1和Bcl-2蛋白的表达;实时荧光定量 PCR(Real-time PCR, RT-PCR)检测不同浓度曲古霉素对肝癌HepG2细胞中Beclin1和Bcl-2 mRNA的表达。结果 曲古霉素对肝癌HepG2细胞具有增殖抑制作用,与对照组相比较,其差异有统计学意义(P＜0.05);通过流式细胞术检测结果显示,曲古霉素作用于肝癌HepG2细胞后,随着浓度的增加,细胞凋亡率显著上升,与对照组相比,差异有统计学意义(P＜0.05);RT-PCR及WB实验观察到,Beclin1蛋白和mMRA的表达随着曲古霉素浓度的增加而逐渐升高,Bcl-2蛋白和mMRA的表达随着曲古霉素作用浓度的增加而逐渐降低,且与对照组相比,其差异均有统计学意义(P＜0.05)。结论 曲古霉素能抑制肝癌细胞的增殖,而且这种作用机制与诱导肝癌细胞凋亡和自噬作用有相关性。

Objective To investigate whether histone deacetylase inhibitor hachimycin has an effect on the proliferation and apoptosis of hepatocellular carcinoma cells and whether the inhibition is related to autophagy. Methods MTT assay was used to detect the proliferation ability of HepG2 cells treated with hachimycin of different concentrations for 24 h, 48 h and 72 h.Flow cytometry was used to detect the effects of different concentrations of hachimycin on HepG2 hepatoma cell cycle and apoptosis.Western blot (WB) assay was used to detect Beclin1 and Bcl-2 expressions in hepatocellular carcinoma HepG2 cells under different hachimycin concentrations.Beclin1 and Bcl-2 mRNA expressions under different hachimycin concentrations in hepatocellular carcinoma HepG2 cells were detected by RT-PCR. Results Hachimycin inhibited the proliferation of HepG2 cells, compared with the control group, the difference was statistically significant (P<0.05). Flow cytometry results showed that the apoptosis rate of hepatocellular carcinoma HepG2 cells was significantly increased with the increase of hachimycin concentration, compared with the control group, the difference was statistically significant (P<0.05). RT-PCR and WB results showed that Beclin1 protein and mMRA expression gradually increased with the increase of hachimycin concentration, while Bcl-2 protein and mMRA expression gradually decreased, compared with the control group, the differences were statistically significant (P<0.05). Conclusion Hachimycin could inhibit the proliferation of hepatocellular carcinoma cells, and its mechanism was related to the induction of apoptosis and autophagy.

目的 系统评价胰岛素联用α-葡萄糖苷酶抑制剂(AGIs)治疗成人1型糖尿病(T1DM)的疗效和安全性。方法 检索中英文数据库,纳入关于胰岛素联用AGIs治疗成人T1DM患者的随机或非随机对照试验。使用Review Manager 5.3软件进行Meta分析。结果 共纳入10项研究,616例患者。与安慰剂或空白对照相比,在有效性方面,胰岛素联合AGIs可改善成人T1DM患者的糖化血红蛋白;降低平均血糖、空腹血糖和餐后2小时血糖;改善血糖波动情况,包括平均血糖波动幅度和最大血糖波动幅度(均P<0.05)。在安全性方面,AGIs增加总不良反应发生的风险(P<0.05),其中主要是胃肠道不适,但未增加低血糖的发生率和发生次数(均P>0.05)。胰岛素联合AGIs减少了每日胰岛素总剂量(P<0.05),但对体重、甘油三酯和高密度脂蛋白胆固醇无显著影响(均P>0.05)。结论 胰岛素联合AGIs可降低成人T1DM患者的糖化血红蛋白,改善血糖水平和血糖波动情况。AGIs不会增加低血糖的风险,但需重视其不良反应,特别是胃肠道不良反应。

Objective To systematically evaluate the efficacy and safety of adding alpha-glucosidase inhibitors (AGIs) to insulin therapy in adult patients with type 1 diabetes (T1DM). Methods Articles about randomized or non-randomized controlled trials of insulin combined with AGIs in adult patients with T1DM were retrieved from Chinese and English database. Meta-analyses were performed by using Review Manager 5.3. Results A total of 616 patients were included from 10 clinical trials. Compared with adding placebo or nothing, in terms of efficacy, the addition of AGIs resulted in decreased HbA1c, mean blood glucose, fasting plasma blood glucose and 2-hour postprandial blood glucose levels (all P<0.05). And this scheme improved the glucose variability including mean amplitude of glycemic excursions and the largest amplitude of glycemic excursions (P<0.05, respectively). As to safety, AGIs increased the risk of total adverse reactions (P<0.05), most of them were gastrointestinal complaints, while the occurrence and the frequency of hypoglycemia were similar (P>0.05, respectively). This scheme could also lead to the reduced total daily insulin dose (P<0.05) but had no significant effect on body weight, triglyceride or cholesterol concentration (P>0.05, respectively). Conclusions The addition of AGIs to insulin therapy in adult patients with T1DM may reduce HbA1c and improve the glucose levels and glucose variability. But total adverse effects especially the gastrointestinal complaints should also be considered in the use of AGIs although it does not increase the risk of hypoglycemia.

目的 研究布拉酵母菌与锌制剂联合应用对小儿迁延性腹泻患儿治疗的效果。方法 选取我院2017年1月—2017年12月收治的136例小儿迁延性腹泻患儿,将其随机分为联合组和对照组,每组各68例患儿,在基础补液、治疗的基础上,联合组采用布拉酵母菌药物联合锌制剂治疗,对照组单纯利用锌制剂治疗,比较两组治疗效果。结果 联合组总有效率97.06%,不良反应发生率4.41%,对照组总有效率88.24%,不良反应发生率14.71%,差异有统计学意义（P<0.05）。联合组患儿血检指标、锌含量、住院时间等指标与对照组比较有差异,（P<0.05）。结论 小儿迁延性腹泻是指患儿的腹泻症状迁延不愈造成严重的肠道炎症,患儿利用基础治疗效果不明显,加用布拉酵母菌与锌制剂对患儿治疗效果的改善作用明显。

目的 分析2009—2011年惠州市区医院三七总皂苷制剂的用药情况,并评价其安全性。方法 根据惠州市区医院2009—2011年三七总皂苷制剂的用药金额和用药量以及药品DDD值,计算其DDDs,分析药品的用药金额排序、DDDs排序以及用药金额排序与DDDs排序的比值;从药物不良反应报告评价其安全性。结果 三七总皂苷制剂用药金额和DDDs逐年增加,口服制剂安全性优于注射剂。结论 三七总皂苷制剂用药金额和用药频度逐年增加,其安全性较好。

Objective To analyse the usage and safety of Panax Notoginseng Saponins Drugs of hospitals in Huizhou from 2009 to 2011. Methods Calculate the DDDs and analyse the sequence of consumption sum, the sequence of DDDs, the ratio of the sequence of consumption sum to the sequence of DDDs according to the consumption sum, the consumption amount and DDD of Panax Notoginseng Saponins Drugs of hospitals in Huizhou from 2009 to 2011. We evaluated its safety according to adverse event reports. Results The consumption sum and DDDs increased year by year, oral medication was safer than injection. Conclusion The consumption sum and DDDs of Panax Notoginseng Saponins drugs of hospitals in Huizhou increase year by year, and they are safe.

目的 探讨磷酸二酯酶4抑制剂对人肺泡巨噬细胞(AM)吞噬非生物性颗粒及革兰阳性菌、阴性菌能力的影响。方法 使用Ficolll-Hypaque密度梯度法将外周血单核细胞分离的静脉血,在含有2 ng/m GM-CSF的培养液中经12天诱导培养成AM替代细胞模型—单核细胞源性巨噬细胞(MDM)。用酶标仪检测MDM经磷酸二酯酶4抑制剂Rolipram预处理过夜(16~18 h)后吞噬荧光标记的非生物颗粒Beads和热灭活的流感嗜血杆菌(H.influenzae)、金黄色葡萄球菌(S.aureus)量的改变,另使用MTT法检测细胞活性。结果 成功建立的MDM细胞模型对Beads和细菌的吞噬呈时效关。Rolipram在实验浓度(10^~8~10^-5 M)下对MDM吞噬Beads、H.influenzae和S.aureus能力无明显促进或抑制作用,也不影响MDM的活性。结论 磷酸二酯酶4抑制剂不会因升高巨噬细胞内cAMP水平而影响其吞噬非生物颗粒和细菌的能力。

Objective To investigate the influence of phosphodiesterases 4 inhibitor on the phagocytosis of non-biological particles and gram-positive bacteria, gram-negative bacteria by human alveolar macrophages. Methods Peripheral blood mononuclear cells (PBMCs) were isolated from venous blood from 12 healthy volunteers using Ficoll-Hypaque density gradients. Monocytes were incubated with media containing 2 ng/ml GM-CSF for 12d to allow full differentiation into macrophage (MDM), a functionally equivalent model of human AM. MDM were pretreated with Rolipram overnight (16-18h),phagocytosis of fluorescent labeled beads and H.influenzae,S.aureus by MDM was measured using a fluostar optima fluorimeter. Cell viability was assay with MTT. Results MDM phagocytosis of beads and bacteria was a time-dependant process. Rolipram in the concentration of 10^-8-10^-5M didn't inhibit or promote phagocytosis of beads and bacteria by MDM, and didn't affect the cell viability. Conclusion Phosphodiesterases 4 inhibitor would not affect the human macrophage phagocytic capacity of non-biological particles and bacteria associated with enhanced intracellular cAMP level.