目的 分析基底节区脑出血患者接受神经内镜手术治疗的疗效。方法 将2019年6月—2020年8月接诊且行开颅血肿清除术的33例基底节区脑出血患者作为对照组,将同期接诊且行神经内镜手术的33例基底节区脑出血患者作为观察组,对组间美国国立卫生研究院卒中量表(NIHSS)、独立功能量表(FIM)、日常生活能力(ADL)评分、手术情况、血清水通道蛋白4(AQP4)水平、脑水肿体积、并发症情况展开分析。结果 (1)组间NIHSS、FIM、ADL评分在术前无明显差异,P>0.05;术后,观察组NIHSS评分更低,且FIM、ADL评分更高,P<0.05;(2)观察组骨窗大小(2.53±0.66)cm、切口长度(4.22±0.67)cm、术中失血量(47.58±11.25)mL、手术用时(1.58±0.42)h均少于对照组(10.88±1.13)cm、(11.84±2.31)cm、(149.83±33.76)mL、(2.99±0.63)h,且血肿清除率(88.84±9.62)%大于对照组(75.31±7.24)%,P<0.05;(3)观察组术后1周、术后2周、术后1个月时的AQP4水平、脑水肿体积均小于对照组,P<0.05;(4)观察组发生1例并发症(3.03%),对照组发生7例并发症(21.21%),P<0.05。结论 对基底节区脑出血患者进行神经内镜手术治疗,手术创伤小,可以降低AQP4水平,减少脑水肿体积及并发症,提高生活能力,值得推广。

Objective To analyze the curative effect of neuroendoscopic surgery in patients with basal ganglia intracerebral hemorrhage. Methods From June 2019 to August 2020, 33 patients with basal ganglia intracerebral hemorrhage who received craniotomy and hematoma clearance were selected as the control group, and 33 patients with basal ganglia intracerebral hemorrhage who received neuroendoscopic surgery at the same period were selected as the observation group. NIHSS,FIM and ADL scores,details of the surgery, levels of AQP4, brain edema volume and complications were analyzed. Results (1) There were no significant differences in NIHSS, FIM and ADL scores between the two groups before operation, P＞0.05; after operation, NIHSS score of the observation group was lower, and FIM and ADL scores were higher, P＜0.05. (2) Bone window size of the observation group was (2.53±0.66) cm, incision length was (4.22±0.67) cm, intraoperative blood loss was (47.58±11.25) mL, and operation time was (1.58±0.42) h, which were less than those of the control group [(10.88±1.13) cm and (11.84±2.31) cm, (149.83±33.76) mL, (2.99±0.63) h], and the hematoma clearance rate (88.84±9.62)% was higher than that of the control group (75.31±7.24)%, P＜0.05. (3) The AQP4 level and brain edema volume of the observation group 1 week, 2 weeks and 1 month after operation were lower than those of the control group, P＜0.05. (4) There was one complication (3.03%) in the observation group and seven complications (21.21%) in the control group,P<0.05. Conclusion Neuroendoscopic surgery for patients with basal ganglia cerebral hemorrhage can reduce the level of AQP4, the volume of brain edema and complications, and improve the ability of life, which is worthy of promotion.

目的 分析人脑胶质瘤组织中O6—甲基鸟嘌呤—DNA甲基转移酶(MGMT)、DNA拓扑异构酶Ⅱ(TopoⅡ)基因的表达情况及其对化疗敏感性的影响。方法 收集医院2012年4月—2018年6月期间进行开颅手术切除的新鲜人脑胶质瘤标本80例和同期经颅脑手术治疗的脑外伤或脑出血内减压切除的正常脑组织30例。采用免疫组化法检测两种标本中MGMT和TopoⅡ基因表达情况,并通过脑胶质瘤U251和U87细胞培养、体外药物(替莫唑胺)干预、Transwell体外侵袭实验分析其对化疗敏感性的影响。结果 胶质瘤标本、正常脑组织MGMT和TopoⅡ基因表达程度分布比较差异均有统计学意义(P＜0.05),且二者MGMT基因阳性表达率分别为63.75%、3.33%,TopoⅡ基因阳性表达率分别为55.00%、0.00%,差异有统计学意义(P＜0.05)。MGMT、TopoⅡ基因均在细胞核显示为阳性染色。体外药物干预的实验组、未进行药物干预的阴性对照组干预前U251、U87细胞穿膜细胞计数比较无统计学意义(P＞0.05),但干预后实验组U251、U87细胞穿膜细胞计数高于阴性对照组(P＜0.05),干预后实验组U251、U87细胞有更强的侵袭力。结论 MGMT和TopoⅡ基因在人脑胶质瘤标本中阳性表达率高,且可能参与促进脑胶质瘤细胞侵袭,影响肿瘤化疗敏感性。

Objective To analyze the expression of O6-methylguanine-DNA methyltransferase (MGMT) and DNA topoisomerase II (Topo II) genes in human brain gliomas and its influence on the chemosensitivity. Methods A total of 80 fresh human brain glioma specimens resected by craniotomy and 30 normal brain tissues resected by craniocerebral operation for traumatic brain injury or decompression for cerebral hemorrhage during the period from April 2012 to June 2017 were collected. The expression of MGMT and Topo II genes in the two kinds of specimens was detected by immunohistochemical method, and the influence on chemosensitivity was analyzed through brain glioma U251 and U87 cell culture, in vitro drug (temozolomide) intervention and Transwell invasion in vitro. Results There was a significant difference in the expression of MGMT and Topo II genes in glioma specimens and normal brain tissues (P<0.05). The positive expression rates of MGMT gene in the two kinds of specimens were 63.75% and 3.33% respectively while the positive expression rates of Topo II gene were 55.00% and 0.00%, respectively (P<0.05). Both of MGMT and Topo II genes were displayed in the nucleus as positive staining. There was no significant difference in transmembrane cell count of U251 and U87 cells between the experimental group given drug intervention in vitro and negative control group without drug intervention before the intervention (P>0.05). However, the transmembrane cell count of U251 and U87 cells in the experimental group after intervention was higher than that in the negative control group (P<0.05). After intervetion, U251 and U87 cells were with stronger invasiveness in the experimental group. Conclusion The positive expression rates of MGMT and Topo II genes are high in human brain glioma specimens. They may be involved in promoting glioma cell invasion, affecting tumor chemosensitivity.

目的 分析神经营养类药物单唾液酸四己糖神经节苷脂(monosialotetrahexosylganglioside,GM1)与胞磷胆碱(citicoline)联合使用在新生儿缺血缺氧性脑病(neonatal hypoxic-ischemic encephalopathy,NHIE)的临床疗效并探讨其可能的作用机制。方法 收集2014年1月—2017年6月在广州市第一人民医院新生儿病房住院的54例新生儿缺血缺氧性脑病患儿的临床资料,将收集到的患儿随机分为2组,对照组27例,治疗组27例。治疗组与对照组的治疗的不同在于前者予以单唾液酸四己糖神经节苷脂GM1联合胞磷胆碱治疗,而对照组仅用单唾液酸四己糖神经节苷脂GM1,无用胞磷胆碱。治疗三个疗程后,比较2组用药前后的临床表现、神经功能评分及MRI变化情况。结果 治疗组中临床总有效24例(88.9%);对照组中总有效17例(63.0%)(P<0.05);经过三个疗程后2组的神经功能评分均有上升,且治疗组的效果更明显(P<0.05);MRI检查示2组较用药前病灶范围减少,水肿减轻,治疗组改善更明显(P<0.05)。即经过三个疗程治疗后,两组患儿病情均有好转,且治疗组疗效更明显。结论 神经营养类药物GM1联合胞磷胆碱通过修复、重构神经元、改善其代谢等促进受损的神经功能的恢复,在新生儿缺血缺氧性脑病的应用中具有良好的疗效。

Objective To analysis the clinical therapeutic effect of monosialotetrahexosylganglioside and citicolineon neonatal hypoxic-ischemic encephalopathy, and explore its possible mechanism.Methods A total of 54 newborn with hypoxicischemic encephalopathy were enrolled from January 2015 to June 2017 in Guangzhou First People's Hospital, and they were divided into control group and treatment group according to the treatment methods, with 27 cases in the control group and 27 cases in the treatment group. Both groups were treated with conventional treatment, the control group added gangliosides, and the treatment group used ganglioside and citicoline. The clinical effects, neurological score and MRI were observed in the two groups.Results The total effective rate was 88.9% in the treatment group,which was higher than 73.0% in the control group (P<0.05). There was no significant difference on neurological score between the two groups before treatment (P>0.05). After treatment, the neurological scores of the two groups were significantly improved, and the score of the treatment group was higher than that of the control group (P<0.05). MRI examinations found that the lesions were significantly improved in the two groups after treatments, and the effect of the treatment group was higher than that of the control group (P<0.05).Conclusion Monosialotetrahexosylganglioside combined with citicolineinthe in treatment of newborn with hypoxicischemic encephalopathy has good effects through repairing and rebuilding the neurons, improving the metabolism to promote the recovery of neurological functions.

目的 评价鞘内注射雷帕霉素对CCI神经病理性痛大鼠的痛阈及脊髓背角胶质细胞表达的影响。方法 健康雄性SD大鼠30只随机分为6组:①CCI组:CCI术后14天处死;②正常对照组:不做任何处理; ③前对照剂组:鞘内置管3天后行CCI术,术后4小时后鞘内给同体积生理盐水,连给3天; ④前给药组:鞘内置管3天后行CCI术,术后4小时鞘内给雷帕霉素溶液,连给3天; ⑤后对照剂组:鞘内置管3天后行CCI术,术后7天鞘内给同体积生理盐水,连给3天;⑥后给药组:鞘内置管3天后行CCI术,术后7天鞘内给雷帕霉素溶液,连给3天。各组于CCI术前1天和术后第2、4、6、8、10、12、14天测机械痛阈和热痛阈。术后14天测痛后用多聚甲醛灌注大鼠,取L4~5脊髓,免疫组化染色,星形胶质细胞标记蛋白(GFAP)检测星形胶质细胞表达变化,并定量分析。结果 与对照组相比,CCI手术组热痛阈和机械痛阈从CCI手术后第4天开始下降(P<0.05);前后给药对照剂组与CCI组相比,差别无统计学意义(P>0.05)。前给药组痛阈从CCI手术后第4天开始上升并持续至手术后第14天,与CCI组相比,差别有统计学意义 (P<0.05)。与CCI组相比,后给药组痛阈从CCI第8天开始上升并持续至手术后第14天,差别有统计学意义(P<0.05)。 与正常对照组比较,CCI组、前、后对照剂组手术侧脊髓背角GFAP染色阳性区平均光密度与阳性面积均有增加,差别有统计学意义(P<0.05)。前、后给药组手术侧GFAP染色阳性区平均光密度与阳性面积与CCI组比较,均有明显降低,差别有统计学意义(P<0.05)。结论 鞘内注射雷帕霉素可缓解大鼠神经病理性痛,并抑制脊髓背角胶质细胞的激活。

Objective To evaluate the effects of intrathecal injection of rapamycin on pain threshold and spinal cord gliacyte activation in rats of neuropathic pain. Methods Healthy 30 male SD rats were randomly divided into 6 groups(n=5 in each group): ① control group without operation or intrathecal injection. ②CCI group without intrathecal injection. ③ intrathecal injection of rapamycin 10 μg(10 μL) 4 hours after CCI operation and the next 2 days once a day. ④ intrathecal injection of NS10 μL 4 hours after CCI operation and the next 2 days once a day. ⑤ intrathecal injection of rapamycin 10 μg(10 μL) 7 days after CCI operation and the next 2 days once a day.⑥ intrathecal injection of NS10 μL 7 days after CCI operation and the next 2 days once a day. Mechanical and thermal threshold were tested 1 day before the CCI operation and 2^th、4^th、6^th、8^th、10^th、12^th、14^th days after the CCI operation for all the rats. Lumbar segment of spinal cords was removed for determination of glial fibrillary acidic protein(GEAP) in spinal cord by immuohistochemistry dyeing and assay in the 14th day after CCI operation for all the rats. Results Mechanical and thermal hyperalgesia emerged on 4th day and maintained till 14th day after CCI operation(P<0.05). After intrathecal injection of rapamycin 4 hours or 7days after CCI, mechanical and thermal threshold significantly increased compared to intrathecal injection of NS(P<0.05). And the sum area of GFAP positive and the mean density of GFAP positive area in the dorsal horn of operation side greatly increased in rapamycin treated groups compared NS treated groups(P<0.05). Conclusion Intrathecal injection of rapamycin may attenuate CCI induced hyperalgesia and inhibit the activation of astrocyte.

目的 探讨DPP-4抑制剂西格列汀对成人隐匿性自身免疫性糖尿病(LADA)早期患者胰岛β细胞功能的影响。方法 把14例新诊断为LADA患者随机分为两组,胰岛素治疗100 mg/d西格列汀(A组,n=7)或无西格列汀(B组,n=7)共治疗9个月。结果 9个月后两组之间的血糖和糖化血红蛋白水平无差异。9个月后A组空腹C肽(FCP),餐后C肽(CP),和ΔCP(ΔCP=2 h CP-FCP)水平与基线相比无明显差别(P＞0.05),B组FCP,2 h的CP和ΔCP进行比较基线显著下降(P<0.05)。A组2 h CP水平明显高于B组(P<0.05)。结论 胰岛素与西格列汀联用较单用胰岛素治疗成人隐匿性自身免疫糖尿病早期患者似乎能更好保护胰岛β细胞功能,西格列汀或可延长LADA非胰岛素依赖期的时间。

Objective The Objective of the study was to investigate the effects of the DPP-4 inhibitor on β-cell function in patients with recent-onset latent autoimmune diabetes in adults LADA. Methods Fourteen recently diagnosed LADA patients were randomized into two groups, A and B, to receive insulin therapy with 100 mg/d sitagliptin (group A, n=7) or without sitagliptin (group B, n=7) for 9 months. Results There were no differences in the clinical baseline data between the two groups. During the 9 months of follow-up, there were no significant differences in glucose and glycosylated hemoglobin levels between the two groups. At 9 months, there were not different in group A including fasting C-peptide (FCP), 2-hour postprandial C-peptide (CP), and ΔCP(ΔCP=2 h CP-FCP) levels (P>0.05). Compared with baseline, whereas in group B the levels of FCP, 2-hour CP and ΔCP were significantly decreased compared with baseline (P<0.05). Levels of 2-hour CP were higher in group A, it was higher than group B at 9 months (P<0.05). Conclusion LADA patients treated with sitagliptin and insulin was more likely maintain β-cell function by comparison with insulin alone. Sitagliptin administration in patients with LADA might prolong the insulin-free period.

目的 观察紫河车提取物联合顺铂对人脑胶质瘤细胞增殖与凋亡的影响。方法 把正常培养传代后的U251胶质瘤细胞按随机分配的方法分为四组,A组仅加普通培养液,B、C、D组各加紫河车提取物(400 mg/mL)2 mL、顺铂(1 mg/mL)0.01 mL、紫河车提取物(400 mg/mL)2 mL＋顺铂(1 mg/mL)0.01 mL;MTT法观察U251细胞增殖情况,流式细胞仪检测U251细胞凋亡率。结果 培养12、24、36、48、60 h,B、C、D组细胞增殖指数逐渐下降,与A组进行比较,各组P值均小于0.05;其中,将D组与B、C组进行比较,P值小于0.05。将各组培养24 h后上机,测得A、B、C、D各组细胞的凋亡率分别为(0.3±0.2)%,(10.6±1.5)%,(35.9±2.8)%,(52.1±4.1)%。其中,B、C、D各组和A组进行比较,P值均小于0.05;将D组与B、C组两组进行比较,P值也均小于0.05。结论 紫河车提取物联合顺铂可抑制人脑胶质瘤U251细胞增殖,并诱导其凋亡。

Objective To observe the effect of cisplatin combinated with the placental immunoregulating polypeptide (PIP) on proliferation and apoptosis of glioma cells. Methods Randomly we divide the normal handed U251 glioma cells into four groups. We added ordinary nutrient solution to group A, while added activated PIP(400 mg/mL)2 mL to group B, cisplatin (1 mg/ml) 0.01 ml to group C, PIP 400 mg/mL)2 mL and cisplatin (1 mg/mL) 0.01 mL to group D. We surveyed the proliferation rate of gliobma cells by MTT experimental method and analyzed the apoptosis of U251 glioma cells by flow cytometry. Results The index of cell proliferation of group B,C,D declined gradually with the training of 12 h,24 h,36 h,48 h,60 h. Compared B, C,D group with A group, P<0.05,and compared group D with group B and group C, P< 0.05. Put groups culturing of 24 hour on flow cytometer, the glioma cells apoptosis rate of each group was 0.3%±0.2%、10.6%±1.5%、35.9%±2.8%、52.1%±4.1% respectively. Compared group B,C,D with group A, P<0.05,and compared group D with group B and group C, P<0.05. Conclusion Placental immunoregulatingpPolypeptide combined with cisplatin may restrain the proliferation of human glioma cells, meanwhile increase the apoptosis of glioma cells.

目的 观察单唾液酸四己糖神经节苷脂联合复方丹参片在治疗难治性癫痫的脑保护作用。方法 选取2010年1月—2015年10月于我院进行治疗的80例难治性癫痫患者为研究对象,随机分为对照组和治疗组。对照组患者给予常规抗癫痫药物治疗,而治疗组患者在对照组治疗基础上给予单唾液酸四己糖神经节苷脂联合复方丹参片治疗。治疗一疗程后,对两组患者进行疗效判定;并分别在治疗前后使用韦氏成人智力量表(WAIS-RC)和韦氏记忆量表(WMS-RC)对两组患者的智商和记忆商进行测评,并比较分析。结果 ①观察组患者的治疗总有效率为97.5%高于对照组的87.5%(P<0.05)。②治疗后,观察组患者的语言智商、操作智商、总智商和记忆商得分分别为(95.4±8.5)分、(94.8±12.5)分、(92.8±7.5)分和(93.5±8.2)分,均高于治疗前的(89.5±7.2)分、(91.5±10.1)分、(88.5±6.9)分和(82.5±10.0)分,且也均高于对照组治疗后的(75.4±6.8)分、(80.6±9.8)分、(80.1±5.9)分和(76.9±8.2)分,以上差异均有统计学意义(P<0.05)。治疗后,对照组患者的智商和记忆商均见的下降,均低于治疗前各分数,以上差异有统计学意义(P<0.05)。结论 神经节苷脂联合复方丹参片治疗难治性癫痫临床效果显著,且具有一定的脑保护效果,可为以后临床治疗难治性癫痫患者提供参考依据。

Objective To observe the cerebral protective effects of monomial four hexose ganglioside combined with compound salvia miltrorrhiza tablets (CSMT) in patients with refractory epilepsy. Methods 80 patients with refractory epilepsy patients treated in our hospital between January 2010 and October 2015 were randomly divided into control group and treatment group. The control group patients were treated with conventional antiepileptic drug therapy, and the treatment group patients were treated with monomial four hexose ganglioside, CSMT and conventional antiepileptic drug therapy. The efficacy in two groups' patients was determined after a course of treatment. The IQ and memory quotient in two groups' patients before and after treatment were evaluated by the Wechsler Adult Intelligence Scale (WAIS-RC) and the Wechsler Memory Scale (WMS-RC) respectively and comparative analysed. Results ①The total effective rate in the treatment group (97.5%) was significantly higher than that in the control group (87.5%) (P<0.05). ②The verbal IQ (95.4±8.5), performance IQ (94.8 ± 12.5), total IQ (92.8 ± 7.5) and memory quotient (93.5 ± 8.2) scores in the treatment group after treatment were significantly higher than those before treatment (89.5 ± 7.2), (91.5 ± 10.1), (88.5 ± 6.9), (82.5 ± 10.0) respectively, and also were significantly higher than those in the control group after treatment (75.4 ± 6.8), (80.6 ± 9.8), (80.1 ± 5.9) and (76.9 ± 8.2) respectively (P<0.05). The IQ and memory quotient in the control groups' patients after treatment were significantly decline and lower than before treatment, which had a statistically significant difference (P<0.05). Conclusion Ganglioside combined with CSMT in the treatment of refractory epilepsy can receive significant clinical effect and own a certain brain protective effect, which provide reference to the future clinical treatment of refractory epilepsy patients.

目的 探讨内科治疗的高血压基底节区出血的疗效及预后相关的因素。方法 回顾性分析2005年4月—2014年12月贵阳市第二人民医院神经外科收治的174例高血压脑出血患者的临床资料,所有患者均采用内科保守治疗,对疗效及影响患者预后的因素进行分析。结果 174例患者中,死亡50例,持续植物生存状态4例,对124例存活患者进行随访,随访时间2~117个月,随访ADL分级Ⅰ级43例,Ⅱ级53例,Ⅲ级21例,Ⅳ级3例,Ⅴ级4例,预后较好者(ADL分级Ⅰ~Ⅱ级)96例,预后不良者(ADL分级Ⅲ~Ⅴ级)28例。χ²检验显示入院 GCS评分和出血量是影响患者预后的因素。结论 影响高血压基底节区脑出血患者的预后因素较多,GCS评分较高、出血量少的患者可采用内科治疗,多数患者预后较好。

Objective To investigate treatment efficacy and the factors influencing prognosis of conservative treatment of hypertensive intracerebral hemorrhage in basal ganglia. Methods A retrospective analysis was conducted on the clinical data of 174 patients with hypertensive intracerebral hemorrhage in basal ganglia who were admitted to our hospital during the period from April 2005 to December 2014. All the patients were given internal medicine conservative treatment and followed up to observe the clinical curative effect to analyze the prognosis. Results Of the 174 patients, 50 patients died and 4 patients were persistent vegetative state. 124 patients were followed up for 2-117 months and they were classified according to ability of daily life(ADL) prognosis scale: 43 cases were in I grade, 53 cases in II grade, 21 cases in III grade, 3 cases in IV grade, 4 cases in V grade. 96 cases achieved favourable outcomes and 28 cases got poor outcomes.The results of Chi square test revealed that GCS scale and intracerebral hemorrhage volume were the factors influencing prognostic of hypertensive intracerebral hemorrhage in basal ganglia. Conclusion There were many prognosis factors related with hypertensive intracerebral hemorrhage. The curative effect and prognosis in patients with conservative treatment is obvious in these patients with high GCS scale and less intracerebral hemorrhage volume.

目的 探讨胃癌组织中刺猬信号通路(Hedgehog signaling pathway, Hh)中的音猬因子(Sonic hedgehog, Shh)和胶质瘤相关癌基因同源物-1(Glioma-associated oncogene homolog -1, Gli-1)与金属基质蛋白酶-2(Matrix metalloproteinase-2, MMP-2)的表达和临床意义。方法 采用免疫组织化学方法检测40例人胃癌组织、人胃息肉组织和40例正常胃黏膜组织中音猬因子、胶质瘤相关癌基因同源物-1、金属基质蛋白酶-2蛋白的表达。结果 胃癌组织中音猬因子、胶质瘤相关癌基因同源物-1、金属基质蛋白酶-2的阳性表达率分别为62.5%、67.5%、72.5%,高于胃息肉组织(阳性表达率分别为27.5%、37.5%、32.5%)和正常胃黏膜组织(阳性表达率分别为22.5%、17.5%、12.5%)(P<0.05);以上三者的表达与患者性别、年龄、组织学类型无关(P>0.05);而与分化程度、浸润深度、淋巴结转移相关(P<0.05);音猬因子、胶质瘤相关癌基因同源物-1、金属基质蛋白酶-2表达呈正相关。结论 刺猬信号通路可能通过某些机制可上调金属基质蛋白酶-2的表达,从而增强胃癌的侵袭性。联合检测胃癌组织中音猬因子、胶质瘤相关癌基因同源物-1、金属基质蛋白酶-2的表达水平在一定程度上可以作为胃癌预后的客观参考指标。

Objective To investigate the expression and clinical significance of Sonic hedgehog(Shh), Glioma-associated oncogene homolog -1(Gli-1) and Matrix metalloproteinase-2(MMP-2) in gastric cancer.Shh and Gli-1 are the molecules of Hedgehog(Hh) signaling pathway. MMP-2 is the member of matrix metalloproteinase family. Methods The expression of Shh,Gli-1 and MMP-2 proteins was examined by immunohistochemistry in the human gastric cancer tissues and the human gastric polyp and the normal gastric mucosa tissues of 40 cases. Results The positive expression rates of Shh,Gli-1 and MMP-2 in gastric cancer were 62.5%,67.5% and 72.5% respectively, which were significantly higher than those in the gastric polyp tissues (the positive expression rates were 27.5%,37.5% and 32.5% respectively) and normal gastric mucosa tissues (the positive expression rates were 22.5%,17.5% and 12.5% respectively),P<0.05.The expression of Shh,Gli-1 and MMP-2 was not correlated with the sex,age or histological type(P>0.05),but was correlated with depth of invasion,differentiation level and lymphonode metastasis in gastric cancer(P<0.05). The expression of Shh and Gli-1 was positive correlated with MMP-2. Conclusion Hedgehog(Hh)signaling pathway may have great effects on enhancing the invasive ability of gastric cancer by upregulating MMP-2 protein through some unknown mechanisms.The combined detection of the expression level of Shh,Gli-1 and MMP-2 in gastric cancer tissues might be used as an Objective references for assessing the prognosis of gastric cancer.

        目的   分析达格列净联合沙库巴曲缬沙坦治疗射血分数降低的心力衰竭（HFrEF）效果。方法  连续抽取2021年1月—2023年6月在广州市第一人民医院心内科住院的射血分数降低的心力衰竭（HFrEF）患者203例，随访至少6个月，按照接受的治疗进行分组。对照组予常规治疗和沙库巴曲缬沙坦治疗；观察组予常规治疗、沙库巴曲缬沙坦和达格列净治疗；对比两组疗效，观察指标包括住院时间，入院及出院后6个月的心功能状态（NYHA纽约心脏病协会心功能分级）、心脏超声指标左室射血分数（LVEF）、左室舒张末内径（LVEDD）、左室收缩末内径（LVSDD）、血液指标-端脑钠肽前体（NT-proBNP N）、糖化血红蛋白（HBA1c）、血肌酐（Cr）、6个月时的再住院率及全因死亡率。结果   观察组心脏监护病房（CCU）停留时间（2.54±1.26）d，短于对照组的（3.73±1.21）d；观察组6个月时观察组心功能NYHA改善≥2级比例为95.05%高于对照组的86.27%，差异有统计学意义（P＜0.05）；观察组6个月时的LVEDD、LVESD水平分别为（48.22±7.35）（34.61±4.32）mm，低于对照组的（51.47±8.02）（43.07±5.33）mm，LVEF为（51.49±5.40）%，高于对照组的（46.18±4.21）%，差异有统计学意义（P＜0.05）；6个月时观察组的NT-proBNP为（415.58±31.57）pg/mL，低于对照组的（520.23±385.56）pg/mL，差异有统计学意义（P＜0.05）；两组的住院时间、血清肌酐（Cr）、HBA1c、6个月时的再住院率、全因病死率对比，差异不显著（P＞0.05）。观察组HBA1c值为（6.04±0.66）mmol/L，高于对照组的（5.20±0.56）mmol/L（P＜0.05）。结论  HFrEF患者采取达格列净+沙库巴曲缬沙坦治疗，可通过协同作用，缩短CCU停留时间，改善患者6个月时的心功能状态，降低NT-proBNP值，减少心脏扩大趋势，提高LVEF水平。

       Objective  To analyze the efficacy of  dapagliflozin combined with  sacubitril/valsartan in the treatment of heart failure with reduced ejection fraction（HFrEF）．Methods  A total of 203 patients with HFrEF who were hospitalized in the cardiology department of the hospital between January 2021 and June 2023 were enrolled and followed up for at least six months．Patients were divided into groups based on their treatment regimens：the control group received conventional treatment plus sacubitril/valsartan，while the observation group received conventional treatment plus sacubitril/valsartan and dapagliflozin．The two groups were compared for clinical outcomes，including length of hospital stay，cardiac function（NYHA classification）at admission and six months after discharge，echocardiographic indicators（LVEF，LVEDD，LVESD），blood indicators（NT-proBNP，HbA1c，creatinine），six-month rehospitalization rate，and all-cause mortality．Results  The observation group had a shorter CCU stay（2.54±1.26 days）compared to the control group（3.73±1.21 days）．At sixth month，the proportion of patients in the observation group with an NYHA improvement ≥2 grades（95.05%）was significantly higher than that in the control group（86.27%）（P＜0.05）．The observation group demonstrated lower LVEDD（48.22±7.35 mm）and LVESD（34.61±4.32 mm）levels and higher LVEF（51.49±5.40%）compared to the control group（LVEDD：［51.47±8.02］ mm，LVESD：［43.07±5.33］mm，LVEF：［46.18±4.21］%）（P＜0.05）．NT-proBNP levels in the observation group（［415.58±31.57］ pg/mL）were significantly lower than those in the control group（［520.23±385.56］ pg/ml）（P＜0.05）．There were no significant differences between the two groups in length of total hospital stay，serum creatinine，HbA1c，six-month rehospitalization rate，or all-cause mortality（P＞0.05）．However，HbA1c levels in the observation group（［6.04±0.66］ mmol/L）were higher than those in the control group（［5.20±0.56］ mmol/L）（P＜0.05）．Conclusions  The combination of dapagliflozin and sacubitril/valsartan in the treatment of HFrEF patients can exert a synergistic effect，shorten CCU stay，improve cardiac function at sixth month，reduce NT-proBNP levels，mitigate cardiac dilation，and increase LVEF．