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目的 观察莪术二酮对肝部分切除的老年小鼠术后认知功能和海马区炎性因子表达的作用。方法 按文献报道方法建立肝部分切除老年小鼠模型,分为假手术组、手术组（模型组）及莪术二酮高、中、低剂量组（造模并药物干预）,另设空白对照组。采用Morris水迷宫评价小鼠的认知功能,采用酶联免疫吸附法检测海马组织中超氧化物歧化酶（SOD）、丙二醛（MDA）、过氧化氢酶（CAT）、谷胱甘肽过氧化物酶（GSH-Px）的水平,Western blot检测海马中NF-κB、白介素-1β（IL-1β）、白介素-6（IL-6）及肿瘤坏死因子（TNF-α）蛋白的表达。结果 手术组动物水迷宫逃逸潜伏期时间明显延长（P〈0.01）,穿台次数显著减少（P〈0.05）;与手术组相比,莪术二酮显著性缩短术后逃逸潜伏期（P〈0.05）,并增加穿台次数（P〈0.05）。肝切除术后海马组织中SOD、CAT和GSH-Px的含量均明显降低（P〈0.05）,MDA含量则明显升高（P〈0.01）。莪术二酮组SOD、CAT和GSH-Px的含量明显升高（P〈0.05）,MDA释放减少（P〈0.05）。莪术二酮组的术后NF-κB、IL-1β、IL-6及TNF-α蛋白的高表达显著抑制（P〈0.05）。结论 莪术二酮可显著改善老年小鼠部分肝切除术后认知功能障碍,其机制可能与其通过抑制海马组织中氧化应激,抑制NF-κB激活,减少炎症细胞因子IL-1β、IL-6及TNF-α的释放有关。

Background Type 2 diabetes mellitus (T2DM) and dementia cause heavy health burden in mainland China, where few studies have investigated the association between glucose‐lowering agents and dementia risk. We aimed to assess the association between use of thiazolidinediones (TZDs) and dementia incidence in a mainland Chinese population with T2DM. Methods A retrospective cohort of T2DM patients who were new users of TZDs or alpha glucosidase inhibitors (AGIs) was assembled using the Yinzhou Regional Health Care Database. A Cox model with inverse probability of treatment weighting (IPTW) for controlling potential founding was applied to estimate the hazard ratio (HR) of the association between use of TZDs and dementia risk. Results A total of 49 823 new users of AGIs and 12 752 new users of TZDs were included in the final cohort. In the primary analysis, the incidence of dementia was 195.7 and 78.2 per 100 000 person‐years in users of AGIs and TZDs respectively. TZD use was associated with a reduced risk of incident dementia after adjusting for potential confounding using IPTW, with a HR of 0.51 (95% CI, 0.38–0.67). The results in various subgroup analyses and sensitivity analyses were consistent with the findings of the primary analysis. Conclusions Use of TZDs is associated with a decreased risk of dementia incidence in a mainland Chinese population with T2DM. 摘要 背景:2型糖尿病(T2DM)和痴呆给患者带来严重的健康负担，但目前很少有研究探讨降糖药物与痴呆风险之间的关系。我们旨在评估T2DM人群中噻唑烷二酮类药物的使用与痴呆发病率之间的关系。 研究设计和方法:利用鄞州地区卫生保健数据库，对新使用噻唑烷二酮(TZDs)或α‐糖苷酶抑制剂(AGIs)的2型糖尿病患者进行回顾性队列研究。采用治疗加权逆概率(IPTW)控制潜在发病的Cox模型来估计TZD使用与痴呆风险之间的关联的风险比(HR)。 结果:最终队列共纳入49823名AGIs新用户和12752名TZDs新用户。在初步分析中，AGIs和TZDs使用者的痴呆发病率分别为每10万人195.7/年和78.2/年。在使用IPTW进行潜在混杂调整后，TZDs的使用与痴呆事件风险降低相关，HR为0.51(95%CI,0.38‐0.67)。不同亚组分析和敏感性分析的结果与初步分析的结果一致。 结论:在2型糖尿病人群中，使用TZDs与痴呆发病率降低相关。 Highlights Type 2 diabetes mellitus (T2DM) and dementia cause heavy health burden in China. This was the first cohort study investigating the association between TZD use and dementia incidence in a mainland Chinese population. We found that TZD use was associated with a 49% reduction in incidence of dementia. Our results could provide some insights into developing effective prevention and control measures to reduce the future disease burden of dementia.

Background Patients with diabetes are more likely to suffer COVID‐19 complications. Using noninsulin antihyperglycemic medications (AGMs) during COVID‐19 infection has proved challenging. In this study, we evaluate different noninsulin AGMs in patients with COVID‐19. Methods We searched Medline, Embase, Web of Science, and Cochrane on 24 January 2022. We used the following keywords (COVID‐19) AND (diabetes mellitus) AND (antihyperglycemic agent). The inclusion criteria were studies reporting one or more of the outcomes. We excluded non‐English articles, case reports, and literature reviews. Study outcomes were mortality, hospitalization, and intensive care unit (ICU) admission. Results The use of metformin rather than other glucose‐lowering medications was associated with statistically significant lower mortality (risk ratio [RR]: 0.60, 95% confidence interval [CI]: 0.47, 0.77, p < .001). Dipeptidyl peptidase‐4 inhibitor (DPP‐4i) use was associated with statistically significantly higher hospitalization risk (RR: 1.44, 95% CI: 1.23, 1.68, p < .001) and higher risk of ICU admissions and/or mechanical ventilation vs nonusers (RR: 1.24, 95% CI: 1.04, 1.48, p < .02). There was a statistically significant decrease in hospitalization for SGLT‐2i users vs nonusers (RR: 0.89, 95% CI: 0.84–0.95, p < .001). Glucagon‐like peptide‐1 receptor agonist (GLP‐1RA) use was associated with a statistically significant decrease in mortality (RR: 0.56, 95% CI: 0.42, 073, p < 0.001), ICU admission, and/or mechanical ventilation (RR: 0.79, 95% CI: 0.69–0.89, p < .001), and hospitalization (RR: 0.73, 95% CI: 0.54, 0.98, p = .04). Conclusions AGM use was not associated with increased mortality. However, metformin and GLP‐1RA use reduced mortality risk statistically significantly. DPP‐4i use was associated with a statistically significant increase in the risk of hospitalization and admission to the ICU. 摘要 背景:糖尿病患者更易罹患COVID‐19并发症。在COVID‐19感染期间使用非胰岛素降糖药物(AGMs)具有挑战性。在本研究中, 我们评估了COVID‐19患者的不同非胰岛素降糖药物。 方法:检索Medline、Embase、Web of Science和Cochrane数据库, 检索时间截至2022年1月24日。我们使用了以下关键词:COVID‐19、糖尿病和降糖药。纳入标准为报告一项或多项结局的研究, 并排除非英文文献、病例报告和文献综述。研究结局包括死亡率、住院和入住ICU。 结果:与其他降糖药物相比, 使用二甲双胍与显著较低的死亡率相关(风险比[RR] 0.60,95% CI 0.47,0.77,p<0.001)。与非使用者相比, 使用DPP‐4i与较高的住院风险(RR 1.44, 95% CI 1.23, 1.68, p<0.001)和较高的ICU入住和/或机械通气风险(RR 1.24, 95% CI 1.04, 1.48, p<0.02)相关。SGLT‐2i用药者的住院率显著低于非用药者(RR 0.89, 95% 0.84 ‐0.95, p <0.001)。胰高血糖素样肽‐1受体激动剂(GLP‐1RA)的使用与死亡率(RR 0.56, 95%CI, 0.42, 073, p<0.001)、入住ICU和/或机械通气(RR 0.79, 95%CI, 0.69‐ 0.89, p<0.001)和住院(RR 0.73, 95%CI 0.54, 0.98, p=0.04)显著降低相关。 结论:AGMs的使用与死亡率增加无关。二甲双胍和GLP‐1RA的使用显著降低了死亡率风险。DPP‐4i的使用与住院和入住ICU的风险显著增加相关。 Highlights Metformin was associated with statistically significantly lower overall mortality for inpatients and outpatients. Dipeptidyl peptidase‐4 inhibitor use was associated with statistically significant higher hospitalization risk and higher risk of intensive care unit (ICU) admissions and/or mechanical ventilation. There was a statistically significant decrease in hospitalization for sodium glucose transporter 2 inhibitor) users vs. nonusers. Glucagon‐like peptide‐1 receptor agonist use was associated with a statistically significant decrease in mortality, ICU admission and/or mechanical ventilation, and hospitalization.

摘要 背景:2型糖尿病(T2DM)和痴呆给患者带来严重的健康负担，但目前很少有研究探讨降糖药物与痴呆风险之间的关系。我们旨在评估T2DM人群中噻唑烷二酮类药物的使用与痴呆发病率之间的关系。 研究设计和方法:利用鄞州地区卫生保健数据库，对新使用噻唑烷二酮(TZDs)或α‐糖苷酶抑制剂(AGIs)的2型糖尿病患者进行回顾性队列研究。采用治疗加权逆概率(IPTW)控制潜在发病的Cox模型来估计TZD使用与痴呆风险之间的关联的风险比(HR)。 结果:最终队列共纳入49823名AGIs新用户和12752名TZDs新用户。在初步分析中，AGIs和TZDs使用者的痴呆发病率分别为每10万人195.7/年和78.2/年。在使用IPTW进行潜在混杂调整后，TZDs的使用与痴呆事件风险降低相关，HR为0.51(95%CI,0.38‐0.67)。不同亚组分析和敏感性分析的结果与初步分析的结果一致。 结论:在2型糖尿病人群中，使用TZDs与痴呆发病率降低相关。

Introduction Diabetic neuropathy is the most prevalent complication of diabetes mellitus. Although the precise etiology of this neurological disorder has yet to be defined, elevated blood glucose promotes anerobic glycolysis; this produces excess advanced glycation end‐products, many of which have a pyrrole structure. Here, we test the hypothesis that protein pyrrole adducts are associated with elevated glucose indices and some clinical features of diabetic diffuse neuropathies. Method We investigated the levels of plasma pyrrole adducts and adjusted urinary pyrrole adducts in a group of elderly persons (n = 516, age 60–79) residing in the District of Luohu, Shenzhen, China between 2017 and 2018. Symptoms of distal symmetric polyneuropathy (DSPN) and resting heart rate, a measure of autonomic nervous system function, were collected from participants (n = 258) with elevated glucose indices. Result Protein pyrrole adducts showed a strong correlation with glucose indices before and after adjustment for age and estimated glomerular filtration rates. Stratified analysis showed that the medians and interquartile values of pyrrole adducts grew as glucose indices of the subgroups increased. Participants with symptoms of DSPN and sinus tachycardia presented elevated levels of plasma pyrrole adducts. Conclusion This study provides a novel link between glucose indices and the etiology of diabetic diffuse neuropathies. 摘要 背景 糖尿病神经病变是糖尿病最常见的并发症。虽然这种神经系统疾病的确切病因尚未确定，但血糖升高会促进无氧糖酵解, 这会产生过量的糖基化终产物，其中许多具有吡咯结构。在本文中，我们探究了吡咯蛋白加合物与血糖指数升高和糖尿病弥漫性神经病的一些临床特征的相关性。 方法 我们调查了2017年至2018年间居住在中国深圳罗湖区的一组老年人(n = 516，年龄 60‐79)的血浆吡咯加合物和校正尿吡咯加合物的水平。从血糖指数升高的参与者 (n=258) 中收集远端对称性多发性神经病(DSPN)的症状以及静息心率(衡量自主神经系统功能的指标)。 结果 蛋白质吡咯加合物在校正年龄和估计肾小球滤过率前后与葡萄糖指数有很强的相关性。分层分析表明，吡咯加合物的中位数和四分位数随着亚组葡萄糖指数的增加而增加。有 DSPN 和窦性心动过速症状的参与者血浆吡咯加合物水平升高。 结论 本研究提供了血糖指数与糖尿病弥漫性神经病病因学之间的新关联。 Highlights The protein pyrrole adducts in both plasma and urine correlated well with glucose indices, namely fasting blood glucose (FBG) and glycate hemoglobin A1c (HbA1c). Elevated plasma pyrrole adducts was related to positive distal symmetric polyneuropathy (DSPN) symptoms and a high resting heart rate. The findings of protein pyrrole adducts build a new bridge between glucose indices and the etiology of DSPN.

摘要 背景 糖尿病神经病变是糖尿病最常见的并发症。虽然这种神经系统疾病的确切病因尚未确定，但血糖升高会促进无氧糖酵解, 这会产生过量的糖基化终产物，其中许多具有吡咯结构。在本文中，我们探究了吡咯蛋白加合物与血糖指数升高和糖尿病弥漫性神经病的一些临床特征的相关性。 方法 我们调查了2017年至2018年间居住在中国深圳罗湖区的一组老年人(n = 516，年龄 60‐79)的血浆吡咯加合物和校正尿吡咯加合物的水平。从血糖指数升高的参与者 (n=258) 中收集远端对称性多发性神经病(DSPN)的症状以及静息心率(衡量自主神经系统功能的指标)。 结果 蛋白质吡咯加合物在校正年龄和估计肾小球滤过率前后与葡萄糖指数有很强的相关性。分层分析表明，吡咯加合物的中位数和四分位数随着亚组葡萄糖指数的增加而增加。有 DSPN 和窦性心动过速症状的参与者血浆吡咯加合物水平升高。 结论 本研究提供了血糖指数与糖尿病弥漫性神经病病因学之间的新关联。

Three new electron donating small molecules （SMs）, Pyr（EH-DPP）2, Pyr（HD-DPP）2 and PyrA（EH-DPP）2, are designed and synthesized through coupling electron rich pyrene core with electron deficient diketopyrrolopyrrole （DPP） terminals, of which the derived organic solar cells （OSCs） exhibit interesting structure-performance correlation. It shows that the tune of their solubilizing side chains and n-bridge for the acceptor-donor-acceptor （A-D-A） SMs can significantly alter the resultant short-circuit current density and power conversion efficiency （PCE） in OSCs. The Pyr（EH-DPP）2 with short side chains displays broader absorption and higher hole mobility than the Pyr（HD-DPP）2 with long side chains. Although showing planar structure, the acetylene bridge-incorporated PyrA（EH-DPP）2 adapts an undesired edge-on packing and strong aggregation in film, leading to non-ideal morphology and poor miscibility with fullerene acceptors. As a result, the PCE of the solar cell based on Pyr（EH-DPP）2 is several times higher than those based on Pyr（HD-DPP）： and PyrA（EH-DPP）2, indicating the A-D-A combination of polyaromatics with DPP would be the promising skeleton for developing photovoltaic semiconductors.

Poly（ethylene glycol）-modified 13-diketone macroligand is developed to sensitize europium（III） ions in water. High lumines cence intensity characteristic of Eu3 was achieved due to spontaneous formation of micelle-like structure in which the hydro phobic core prevents luminescence-quenching by water molecules. The pH is found to induce a quantitative ratio change in two fluorescence bands from both ligand and Eu3.

Aim： To assess the effect of estradiol-17β （E2） and bisphenol A （BPA） administered chronically by implanting a silicone tube throughout pregnancy and lactation on male pups＇ reproductive system in ICR mice. Methods： Female mice were implanted with a tube filled with 10 ng, 500 ng, 1 μg, or 10 μg of E2, or 100 μg or 5 mg of BPA, before mating. The tube was kept in the mice throughout pregnancy and lactation, until the pups had weaned at 4 weeks of age. During the period, E2 was released from the tube at 120 pg or 6, 12 or 120 ng/day, and BPA at 1.2 or 60 μg/day. Results： Most of the mice given 1 μg and 10 lag of E2 did not maintain their pregnancy. However, the other groups showed high rates of birth, more than 70%. At age of 4 weeks, the male pups were killed. Body weight and reproductive organ weights （testes, epididymides and accessory reproductive glands） in the treated groups did not differ from the control values, whereas the percentage of seminiferous tubules in the testis with mature spermatids was significantly lower in the groups given 10 ng and 500 ng of E2 and 5 mg of BPA than that in the control. Conclusion： Chronic exposure to E2 and BPA might disrupt spermatogenesis in male pups. （Asian JAndrol 2008 Mar; 10： 271-276）

We previously isolated a natural product, namely guaiazulene-2,9-dione showing strong antibacterial activity against Vibrio anguillarum, from a gorgonian Muriceides collaris collected in South China Sea. In this experiment, guaiazulene-2,9-dione was quantitatively synthesized with an optimized one-step bromine oxidation method using guaiazulene as the raw material. The key reaction condition including reaction time and temperature, drop rate of bromine, concentration of aqueous THF solution, respective molar ratio of guaiazulene to bromine and acetic acid, and concentration of guaiazulene in aqueous THF solution, were investigated individually at five levels each for optimization. Combined with the verification test to show the absolute yield of each optimization step, the final optimal condition was determined as： when a solution of 0.025mmol mL-1 guaiazulene in 80% aqueous THF was treated with four volumes of bromine at a drop rate of 0.1 mL min 1 and four volumes of acetic acid at -5℃ for three hours, the yield of guaiazulene-2,9-dione was 23.72%. This was the first report concerning optimized one-step synthesis to provide a convenient method for the large preparation of guaiazulene-2,9-dione.