1.Inhibitory Effects of the Slit Guidance Ligand 1-3’ Untranslated Region on the Fibrotic Phenotype of Cardiac Fibroblasts
Ya WANG ; Huayan WU ; Yuan GAO ; Rushi WU ; Peiying GUAN ; Hui LI ; Juntao FANG ; Zhixin SHAN
Journal of Sun Yat-sen University(Medical Sciences) 2025;46(3):466-474
ObjectiveTo study the regulatory effect of the partial sequence within the 3’ untranslated region (3’UTR) of slit guidance ligand 1 (Slit1) (Slit1-3’UTR) on the fibrotic phenotypes of cardiac fibroblasts (CFs) and its potential mechanism. MethodsThe adenovirus vector was used to overexpress the 1526nt sequence of Slit1-3’UTR in ICR neonatal mouse CFs (mCFs). The expression of fibrosis-related genes in mCFs, such as collagen type 1 alpha1(COL1A1), collagen type 3 alpha3 (COL3A1) and alpha smooth muscle actin (α-SMA) were detected by Western blot assay. The effect of Slit1-3’UTR 1526nt on the proliferation and migration of mCFs was assessed by EdU staining and Trans-well assays. Angiotensin Ⅱ (Ang Ⅱ) was used to treat mCFs, and the impact of Slit1-3’UTR 1526nt on the fibrotic phenotypes of Ang Ⅱ-induced mCFs was evaluated. After overexpression of Slit1-3’UTR 1526nt, miR-34a-5p mimic was transfected into mCFs, followed by actinomycin D treatment to detect the mRNA stability of Slit1-3’UTR 1526nt, and the levels of miR-34a-5p and its target gene SIRT1(si-SIRT1) in mCFs were determined. The effects of miR-34a-5p and small interfering RNA targeting SIRT1 on the Slit1-3’UTR 1526nt-mediated regulation of fibrotic phenotypes were also determined. ResultsAdenovirus-mediated overexpression of Slit 1-3’UTR 1526nt was achieved in mCFs. Overexpression of Slit 1-3’UTR 1526nt markedly inhibited the expression of the fibrosis-related genes, proliferation and migration of mCFs and fibrotic phenotypes of Ang Ⅱ. The results of actinomycin D assay showed that miR-34a-5p inhibited the stability of Slit1-3’UTR 1526nt in mCFs, while the level of miR-34a-5p was reduced in mCFs with overexpression of Slit1-3’UTR 1526nt. Transfection of miR-34a-5p promoted the fibrotic phenotypes, and reversed the inhibitory effect of Slit1-3’UTR 1526nt on the fibrotic phenotypes of mCFs. Overexpression of Slit1-3’UTR 1526nt significantly increased the level of miR-34a-5p target gene SIRT1 in mCFs. Transfection of miR-34a-5p and si-SIRT1 consistently reversed the inhibitory effects of Slit1-3’UTR 1526nt on the fibrotic phenotypes of mCFs. ConclusionSlit1-3’UTR1526nt inhibits the fibrotic phenotypes of mCFs by binding to miR-34a-5p and increasing the expression of its target gene of SIRT1.
2.Chemical approaches for the stereocontrolled synthesis of 1,2-cis-β-D-rhamnosides.
Juntao CAI ; Xin YUAN ; Yuanfang KONG ; Yulong HU ; Jieming LI ; Shiqing JIANG ; Chunhong DONG ; Kan DING
Chinese Journal of Natural Medicines (English Ed.) 2023;21(12):886-901
In carbohydrate chemistry, the stereoselective synthesis of 1,2-cis-glycosides remains a formidable challenge. This complexity is comparable to the synthesis of 1,2-cis-β-D-mannosides, primarily due to the adverse anomeric and Δ-2 effects. Over the past decades, to attain β-stereoselectivity in D-rhamnosylation, researchers have devised numerous direct and indirect methodologies, including the hydrogen-bond-mediated aglycone delivery (HAD) method, the synthesis of β-D-mannoside paired with C6 deoxygenation, and the combined approach of 1,2-trans-glycosylation and C2 epimerization. This review elaborates on the advancements in β-D-rhamnosylation and its implications for the total synthesis of tiacumicin B and other physiologically relevant glycans.
Glycosides
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Mannosides
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Glycosylation
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Stereoisomerism
3.Hepatic DDAH1 mitigates hepatic steatosis and insulin resistance in obese mice: Involvement of reduced S100A11 expression.
Xiyue SHEN ; Kai LUO ; Juntao YUAN ; Junling GAO ; Bingqing CUI ; Zhuoran YU ; Zhongbing LU
Acta Pharmaceutica Sinica B 2023;13(8):3352-3364
Dimethylarginine dimethylaminohydrolase 1 (DDAH1) is an important regulator of plasma asymmetric dimethylarginine (ADMA) levels, which are associated with insulin resistance in patients with nonalcoholic fatty liver disease (NAFLD). To elucidate the role of hepatic DDAH1 in the pathogenesis of NAFLD, we used hepatocyte-specific Ddah1-knockout mice (Ddah1HKO) to examine the progress of high-fat diet (HFD)-induced NAFLD. Compared to diet-matched flox/flox littermates (Ddah1f/f), Ddah1HKO mice exhibited higher serum ADMA levels. After HFD feeding for 16 weeks, Ddah1HKO mice developed more severe liver steatosis and worse insulin resistance than Ddah1f/f mice. On the contrary, overexpression of DDAH1 attenuated the NAFLD-like phenotype in HFD-fed mice and ob/ob mice. RNA-seq analysis showed that DDAH1 affects NF-κB signaling, lipid metabolic processes, and immune system processes in fatty livers. Furthermore, DDAH1 reduces S100 calcium-binding protein A11 (S100A11) possibly via NF-κB, JNK and oxidative stress-dependent manner in fatty livers. Knockdown of hepatic S100a11 by an AAV8-shS100a11 vector alleviated hepatic steatosis and insulin resistance in HFD-fed Ddah1HKO mice. In summary, our results suggested that the liver DDAH1/S100A11 axis has a marked effect on liver lipid metabolism in obese mice. Strategies to increase liver DDAH1 activity or decrease S100A11 expression could be a valuable approach for NAFLD therapy.
4.The prognostic effect of pelvic lymph node dissection on the patients undergoing radical cystectomy
Xiao YANG ; Kai LI ; Juntao ZHUANG ; Lingkai CAI ; Qikai WU ; Baorui YUAN ; Hao YU ; Qiang CAO ; Pengchao LI ; Qiang LYU
Chinese Journal of Urology 2023;44(8):606-610
Objective:To discuss the efficacy of pelvic lymph node dissection (PLND) on the patients undergoing radical cystectomy (RC).Methods:The clinicopathological data of bladder cancer patients who did not receive neoadjuvant chemotherapy and underwent RC in our center from November 2013 to December 2019 were collected. The average age of the patients was (67.4±10.9) years, including 284 males and 55 females. Postoperative pathology showed that 171 cases of MIBC and 168 cases of NMIBC. In the MIBC group, 124 patients received PLND. In the NMIBC group, 118 patients received PLND. There was no statistical difference of the PLND ratio between the two groups(72.5% vs. 65.5%, P=0.643). The average number of lymph nodes(LNs)in patients receiving PLND was(13.7±7.1). Explore the prognostic factors in NMIBC and MIBC respectively. The Kaplan-Meier method was used to analyze the effect of PLND on the prognosis of patients in MIBC and NMIBC group. Results:In MIBC group, 26 patients showed positive LNs, while 98 had negative LNs. 144 cases were high-grade urothelial carcinoma, and 47 cases received adjuvant treatment. In NMIBC group, 4 patients exhibited positive LNs, while 114 had negative LNs. 99 cases were high-grade urothelial carcinoma, and 15 cases received adjuvant treatment. After a median follow-up of 24(13, 43)months, Kaplan-Meier survival analysis showed that the 5-year overall survival(OS)of 395 patients was 63.6%. MIBC had a 5-year OS rate of 47.5%, while NMIBC had a rate of 79.1%. Univariate Cox regression showed that age≥65 years( HR=2.07, 95% CI 1.21-3.54, P=0.009), high tumor grade( HR=9.76, 95% CI 2.39-39.90, P<0.01), and positive lymph nodes( HR=2.47, 95% CI 1.27-4.78, P=0.008)were risk factors for the prognosis of MIBC.PLND ( HR=0.37, 95% CI 0.23-0.60, P<0.01) and adjuvant therapy ( HR=0.21, 95% CI 0.10-0.46, P<0.01) were protective factors of MIBC. However, the only risk factor of NMIBC was high tumor grade ( HR=6.66, 95% CI1.51-29.50, P=0.012). PLND had no effect on the prognosis of NMIBC patients following RC( HR=1.32, 95% CI 0.37-4.75, P=0.667). Multivariate COX regression analysis revealed that high tumor grade( HR=6.38, 95% CI 1.54-26.50, P=0.011) was independent risk factor of MIBC, PLND( HR=0.59, 95% CI 0.35-0.99, P=0.047), as well as adjuvant therapy ( HR=0.30, 95% CI 0.13-0.68, P=0.004) were independent protective factors of MIBC. Further analysis discovered that MIBC patients with negative LNs had a better prognosis than those with no PLND (62.4% vs. 16.1%, P<0.01)and positive LNs(62.4% vs.32.3%, P=0.005). However, there was no difference in prognosis between the negative LNs and no PLND group in NMIBC patients (81.3% vs. 66.6%, P=0.764). Conclusions:This study found that PLND was an independent predictive factor for MIBC patients receiving radical cystectomy.
5.The value of VI-RADS score in postoperative prognosis evaluation of bladder cancer patients
Qikai WU ; Xiao YANG ; Baorui YUAN ; Dexiang FENG ; Lingkai CAI ; Juntao ZHUANG ; Kai LI ; Qiang CAO ; Pengchao LI ; Qiang LYU
Chinese Journal of Urology 2023;44(8):611-615
Objective:To investigate the value of the vesical imaging reporting and data system score (VI-RADS) in the prognostic assessment of patients with bladder cancer.Methods:The data of 294 patients with pathologically confirmed bladder cancer in our department from February 2012 to September 2019 were retrospectively analyzed. Divide the patients into two groups based on the surgical method. In the transurethral resection of bladder tumor (TURBT) group, there were 121 cases, 102 males and 19 females; The average age of the patients was (66.7±12.3) years old, 52 cases <65 years old, 69 cases ≥65 years old, with VI-RADS <3 in 84 cases, VI-RADS ≥3 in 37 cases. In the radical cystectomy (RC) group, there were 173 cases, including 154 males and 19 females; The average age of the patients was (65.7±10.8) years, 77 cases <65 years old, 96 cases ≥65 years old, with VI-RADS <3 in 51 cases and VI-RADS ≥3 in 122 cases. The prognostic factors of TURBT group and RC group were analyzed, and the predictive value of VI-RADS score on overall survival (OS) and progression free survival (PFS) of bladder cancer patients after surgery was analyzed.Results:In this study, there were 294 cases with postoperative pathological diagnosis of urothelial carcinoma. The pathological staging was Ta stage in 104 cases (35.4%), T 1stage in 82 cases (27.9%), T 2 stage in 58 cases (19.7%), T 3 stage in 34 cases (11.6%), and T 4stage in 16 cases (5.4%). Pathological grading: 11 cases (3.7%) were low malignant potential, 77 cases (26.2%) were low grade, and 206 cases (70.1%) were high grade. There were 186 cases (63.3%) in the NMIBC group and 108 cases (36.7%) in the MIBC group. In the TURBT group, there were 114 cases (94.2%) in the NMIBC group and 7 cases (5.8%) in the MIBC group; In the RC group, there were 72 cases (41.6%) in the NMIBC group and 101 cases (58.4%) in the MIBC group. In the NMIBC group, the VI-RADS<3 and ≥3 were 128 cases (68.8%) and 58 cases (31.2%), respectively ( P<0.01); In the MIBC group, 101 cases (93.5%) had a VI-RADS <3 and 7 cases (6.5%) had a VI-RADS ≥ 3, respectively ( P<0.01). In the high grade of postoperative pathological group, 62 cases (30.1%) had a VI-RADS <3 and 144 cases (69.9%) had a VI-RADS ≥ 3, respectively ( P<0.01); In the non-high grade of postoperative pathological group, the VI-RADS <3 and ≥ 3 were 73 cases (83.0%) and 15 cases (17.0%), respectively ( P<0.01). The median OS survival for all patients in this study was 27.4 (16.6, 38.1)months and the median PFS survival was 24.7(14.0, 36.8) months. The results of univariate analysis showed that age ≥ 65 years old (OS: HR=6.09, P=0.001; PFS: HR=1.71, P=0.035), postoperative pathological diagnosis of tumor muscle infiltration (OS: HR=4.66, P<0.01; PFS: HR=2.24, P=0.001), postoperative high-grade tumor (OS: HR=4.26, P=0.008; PFS: HR=1.92, P=0.023), and VI-RADS score ≥ 3 (OS: HR=4.24, P=0.001; PFS: HR=2.21, P=0.002) were associated with poorer OS and PFS in patients. Multifactorial Cox model analysis revealed that a score of VI-RADS ≥3 was an independent risk factor for OS ( HR=3.41, P=0.012) and PFS ( HR=2.23, P=0.016). In the TURBT group, univariate analysis found that VI-RADS ≥3 ( HR=2.05, P=0.053) and high grade of postoperative pathology ( HR=2.77, P=0.005) were associated with poor PFS in patients, multifactorial Cox model analysis found only high grade of postoperative pathology ( HR=2.54, P=0.013) to be an independent risk factor for PFS. In the RC group, VI-RADS ≥3 ( HR=3.29, P=0.032) and age ≥65 years ( HR=5.37, P=0.001) were found to be independent risk factors for OS. The survival curve showed that the 5-year OS rates for groups with a VI-RADS ≥ 3 and <3 were 93.9% and 73.1%, respectively ( P<0.01), and the 5-year PFS rates for groups with a VI-RADS ≥ 3 and <3 were 76.5% and 53.0%, respectively ( P<0.01), with statistically significant differences. Conclusions:This study showed that VI-RADS ≥3 was an independent risk factor for prognosis in patients with bladder cancer and was more significant in patients receiving RC, but was not a significant predictor of prognosis in patients receiving TURBT.
6.The prognosis and complications differences between MIBC and NMIBC in the orthotopic ileal neobladder
Lingkai CAI ; Xiao YANG ; Qiang CAO ; Pengchao LI ; Juntao ZHUANG ; Kai LI ; Baorui YUAN ; Qikai WU ; Pengfei SHAO ; Jie LI ; Zengjun WANG ; Qiang LYU
Chinese Journal of Urology 2023;44(9):675-681
Objective:To compare the prognosis and complications of muscle-invasive bladder cancer (MIBC) and non-muscle-invasive bladder cancer (NMIBC) patients undergoing radical cystectomy (RC) followed by ileal neobladder.Methods:The clinical data of 103 patients who underwent orthotopic ileal neobladder in Jiangsu Province Hospital from April 2010 to October 2021 were retrospectively analyzed. There were 51 MIBC patients and 52 NMIBC patients. In the MIBC group, there were 49 males and 2 females, aged (58.1 ± 8.9) years, with American Society of Anesthesiologists (ASA) score of 1-2 in 48 cases and 3 in 3 cases. Open radical cystectomy (ORC) was performed in 2 cases, laparoscopic (LRC) in 34 cases and robot-assisted radical cystectomy (RARC) in 15 cases. In the NMIBC group, there were 49 males and 3 females, aged (55.7 ± 9.9) years, ASA score of 1-2 in 51 cases and ASA score of 3 in 1 case. LRC was performed in 41 cases, and RARC in 11 cases. There were no statistically differences between the two groups in above indicators ( P>0.05). The Clavien-Dindo grading system (CCS) was used to assess the complications, defining CCS Ⅰ-Ⅱ as mild complications and CCS Ⅲ-Ⅴ as severe complications. According to their relationship to the neobladder, complications were be classified as neobladder-related and non-neobladder-related complications. The occurrence of complications and the prognosis of neobladder between MIBC and NMIBC were compared. Results:The average operation time of the MIBC group and NMIBC group were (421.2 ± 119.7) min vs. (439.8 ± 106.2) min. The blood loss were 400 (300, 700) ml vs. 400 (300, 625) ml. The frequency of lymph nodes removed were (14.9 ± 8.3) vs. (14.8 ± 8.5). The postoperative defecation time were 5 (4, 6) d vs. 5 (3, 6) d. And the postoperative hospital stay were 20 (15, 28) d vs. 22 (19, 28) d. There were no statistically differences between the two groups in above indicators ( P>0.05). The MIBC group had a significantly lower rate of pelvic lymph node metastasis [17.6% (9/51) vs. 0(0/52), P=0.001] and tumor thrombosis [23.5% (12/51) vs. 5.8% (3/51), P=0.011] than the MIBC group. Moreover, the NMIBC group had a considerably superior 5-year overall survival (OS) (97.6% vs. 70.2%, P=0.035). The proportion of pads needed in the daytime of the MIBC group and NMIBC group were 14.6% (7/46) vs. 6.7% (3/45). The frequency of urination were (2.0 ± 0.7) h vs. (2.4 ± 0.7) h. Furthermore, The proportion of pads needed at night were 47.9% (23/48) vs. 53.3% (24/45). The frequency of nocturnal urination were 3.1±1.5 vs. 2.3 ± 1.7. And the number of pads needed at night were all 1 (0, 1) pad. The daytime and nighttime incontinence rate were 25.0% (12/48) and 62.5% (30/48) respectively in MIBC, compared to 11.1% (5/45) and 62.2% (28/45) respectively in NMIBC. And the proportion of erectile function retention were 15.8% (6/38) vs. 25.0% (10/40). There were no statistically significant differences in the prognosis of neobladder function between the two groups ( P>0.05). Furthermore, the proportions of mild complications in the MIBC group and NMIBC group were [41.2% (21/51) vs. 51.9 (27/52)]. The proportions of severe complications were [21.6% (11/51) vs. 19.2% (27/52)]. The proportions of neobladder-related complications were [27.5% (14/51) vs. 25.0% (13/52)]. And the proportions of non-neobladder-related complications were [39.2% (20/51) vs. 25.0% (13/52)]. There were no statistically significant differences in the complications between the two groups ( P>0.05). Conclusions:There was no statistically significant difference in functional prognosis and complications of neobladder between MIBC group and NMIBC group, and NMIBC had a better oncologic prognosis.
7.Repair of skin defects of extremities with peroneal artery perforator flap with super-draining techniques
Ye YUAN ; Juntao QIU ; Hui LI ; Fanglin YI ; Gaohui LI ; Zhentao YU ; Liuyong YAO ; Chuang LU
Chinese Journal of Plastic Surgery 2021;37(5):534-540
Objective:To evaluate the clinical effect of applying peroneal artery perforator flap with super-draining techniques in repairing skin defects of extremities.Methods:The data of patients with limb wounds admitted to the 990th Hospital of the Joint Logistics Support Force of the People’s Liberation Army from March 2014 to August 2019 were analyzed retrospectively. All were repaired with peroneal artery perforator flaps with super-draining techniques.Cutaneous nerves and perforating vessels were anastomosed according to the routine ratio of 1∶2.The superficial vein and the recipient veinwere matched and marked according to the relative position the diameter and length.Then one to three superficial veins were anastomosed in sequence according to the vein mark number.Upper limb wounds were evaluated by the trial standard of upper limb function evaluation of the Hand Surgery Branch of the Chinese Medical Association.Patients with lower limb wounds were evaluated by the American Orthopaedic Foot and Ankle Surgery Association Ankle-Hindfoot Score System.All patients were evaluated according to the sensory function evaluation standard of the British Medical Research Association.Results:A total of 67 cases were included in this cohort. There were 54 males and 13 females, aged from 21 to 65 years, with an average of 44 years.Eight cases were anastomosed with three superficial veins, 38 cases were anastomosed with two flaps, and 21 cases were anastomosed with one flap.The donor sites were closed directly in 56 cases.Eleven cases received full-thickness skin grafting to cover the donor site.One case showed necrosis of the half flap for the arterial crisis. The wound was repaired by full-thickness skin grafting in further treatment. Three cases had hemorrhage under the free flap, which was healed secondarily after debridement. The remaining were healed well.All patients were followed for 6 to 44 months. There was no obvious swelling and blisters in the early postoperative period.The texture of the flap was the same as the surrounding area.In the later stage, the atrophy and scar were not obvious, without pigmentation. The sensation recovered quickly. The donor site healed without dysfunction.Sixteen patients with upper limb wounds were evaluated by the trial standard of upper limb function evaluation of the Chinese Medical Association Hand Surgery Branch. Twelve cases were excellent, 3 cases were good, and one case was fair. Fifty-one cases of lower limb wounds were evaluated by the American Orthopaedic Foot and Ankle Surgery Association Ankle-Hind Foot Score System. Thirty-eight cases were excellent, 11 cases were good, and two cases were fair. All patients were evaluated according to the sensory function evaluation standard of the British Medical Research Association. The two-point distance discrimination was 8-10 mm, with an average of 9.1 mm. The sensory function of the flaps reached S3+ in 48 cases and S3 in 19 cases.Conclusions:Application of super-draining technique in peroneal artery perforator flap surgery can effectively prevent blood congestion and reduce the necrosis risk of the free flap and complication rate. It can improve the survival quality of the flap and facilitate the recovery of the function of the receiving area.
8.Repair of skin defects of extremities with peroneal artery perforator flap with super-draining techniques
Ye YUAN ; Juntao QIU ; Hui LI ; Fanglin YI ; Gaohui LI ; Zhentao YU ; Liuyong YAO ; Chuang LU
Chinese Journal of Plastic Surgery 2021;37(5):534-540
Objective:To evaluate the clinical effect of applying peroneal artery perforator flap with super-draining techniques in repairing skin defects of extremities.Methods:The data of patients with limb wounds admitted to the 990th Hospital of the Joint Logistics Support Force of the People’s Liberation Army from March 2014 to August 2019 were analyzed retrospectively. All were repaired with peroneal artery perforator flaps with super-draining techniques.Cutaneous nerves and perforating vessels were anastomosed according to the routine ratio of 1∶2.The superficial vein and the recipient veinwere matched and marked according to the relative position the diameter and length.Then one to three superficial veins were anastomosed in sequence according to the vein mark number.Upper limb wounds were evaluated by the trial standard of upper limb function evaluation of the Hand Surgery Branch of the Chinese Medical Association.Patients with lower limb wounds were evaluated by the American Orthopaedic Foot and Ankle Surgery Association Ankle-Hindfoot Score System.All patients were evaluated according to the sensory function evaluation standard of the British Medical Research Association.Results:A total of 67 cases were included in this cohort. There were 54 males and 13 females, aged from 21 to 65 years, with an average of 44 years.Eight cases were anastomosed with three superficial veins, 38 cases were anastomosed with two flaps, and 21 cases were anastomosed with one flap.The donor sites were closed directly in 56 cases.Eleven cases received full-thickness skin grafting to cover the donor site.One case showed necrosis of the half flap for the arterial crisis. The wound was repaired by full-thickness skin grafting in further treatment. Three cases had hemorrhage under the free flap, which was healed secondarily after debridement. The remaining were healed well.All patients were followed for 6 to 44 months. There was no obvious swelling and blisters in the early postoperative period.The texture of the flap was the same as the surrounding area.In the later stage, the atrophy and scar were not obvious, without pigmentation. The sensation recovered quickly. The donor site healed without dysfunction.Sixteen patients with upper limb wounds were evaluated by the trial standard of upper limb function evaluation of the Chinese Medical Association Hand Surgery Branch. Twelve cases were excellent, 3 cases were good, and one case was fair. Fifty-one cases of lower limb wounds were evaluated by the American Orthopaedic Foot and Ankle Surgery Association Ankle-Hind Foot Score System. Thirty-eight cases were excellent, 11 cases were good, and two cases were fair. All patients were evaluated according to the sensory function evaluation standard of the British Medical Research Association. The two-point distance discrimination was 8-10 mm, with an average of 9.1 mm. The sensory function of the flaps reached S3+ in 48 cases and S3 in 19 cases.Conclusions:Application of super-draining technique in peroneal artery perforator flap surgery can effectively prevent blood congestion and reduce the necrosis risk of the free flap and complication rate. It can improve the survival quality of the flap and facilitate the recovery of the function of the receiving area.
9.Experts consensus on the management of delirium in critically ill patients
Bo TANG ; Xiaoting WANG ; Wenjin CHEN ; Shihong ZHU ; Yangong CHAO ; Bo ZHU ; Wei HE ; Bin WANG ; Fangfang CAO ; Yijun LIU ; Xiaojing FAN ; Hong YANG ; Qianghong XU ; Heng ZHANG ; Ruichen GONG ; Wenzhao CHAI ; Hongmin ZHANG ; Guangzhi SHI ; Lihong LI ; Qibing HUANG ; Lina ZHANG ; Wanhong YIN ; Xiuling SHANG ; Xiaomeng WANG ; Fang TIAN ; Lixia LIU ; Ran ZHU ; Jun WU ; Yaqiu WU ; Chunling LI ; Yuan ZONG ; Juntao HU ; Jiao LIU ; Qian ZHAI ; Lijing DENG ; Yiyun DENG ; Dawei LIU
Chinese Journal of Internal Medicine 2019;58(2):108-118
To establish the experts consensus on the management of delirium in critically ill patients.A special committee was set up by 15 experts from the Chinese Critical Hypothermia-Sedation Therapy Study Group.Each statement was assessed based on the GRADE (Grading of Recommendations Assessment,Development,and Evaluation) principle.Then the Delphi method was adopted by 36 experts to reassess all the statements.(1) Delirium is not only a mental change,but also a clinical syndrome with multiple pathophysiological changes.(2) Delirium is a form of disturbance of consciousness and a manifestation of abnormal brain function.(3) Pain is a common cause of delirium in critically ill patients.Analgesia can reduce the occurrence and development of delirium.(4) Anxiety or depression are important factors for delirium in critically ill patients.(5) The correlation between sedative and analgesic drugs and delirium is uncertain.(6) Pay attention to the relationship between delirium and withdrawal reactions.(7) Pay attention to the relationship between delirium and drug dependence/ withdrawal reactions.(8) Sleep disruption can induce delirium.(9) We should be vigilant against potential risk factors for persistent or recurrent delirium.(10) Critically illness related delirium can affect the diagnosis and treatment of primary diseases,and can also be alleviated with the improvement of primary diseases.(11) Acute change of consciousness and attention deficit are necessary for delirium diagnosis.(12) The combined assessment of confusion assessment method for the intensive care unit and intensive care delirium screening checklist can improve the sensitivity of delirium,especially subclinical delirium.(13) Early identification and intervention of subclinical delirium can reduce its risk of clinical delirium.(14) Daily assessment is helpful for early detection of delirium.(15) Hopoactive delirium and mixed delirium are common and should be emphasized.(16) Delirium may be accompanied by changes in electroencephalogram.Bedside electroencephalogram monitoring should be used in the ICU if conditions warrant.(17) Pay attention to differential diagnosis of delirium and dementia/depression.(18) Pay attention to the role of rapid delirium screening method in delirium management.(19) Assessment of the severity of delirium is an essential part of the diagnosis of delirium.(20) The key to the management of delirium is etiological treatment.(21) Improving environmental factors and making patient comfort can help reduce delirium.(22) Early exercise can reduce the incidence of delirium and shorten the duration of delirium.(23) Communication with patients should be emphasized and strengthened.Family members participation can help reduce the incidence of delirium and promote the recovery of delirium.(24) Pay attention to the role of sleep management in the prevention and treatment of delirium.(25) Dexmedetomidine can shorten the duration of hyperactive delirium or prevent delirium.(26) When using antipsychotics to treat delirium,we should be alert to its effect on the heart rhythm.(27) Delirium management should pay attention to brain functional exercise.(28) Compared with non-critically illness related delirium,the relief of critically illness related delirium will not accomplished at one stroke.(29) Multiple management strategies such as ABCDEF,eCASH and ESCAPE are helpful to prevent and treat delirium and improve the prognosis of critically ill patients.(30) Shortening the duration of delirium can reduce the occurrence of long-term cognitive impairment.(31) Multidisciplinary cooperation and continuous quality improvement can improve delirium management.Consensus can promote delirium management in critically ill patients,optimize analgesia and sedation therapy,and even affect prognosis.
10.Long-term outcome of postpartum glucose metabolism among patients with gestational hyperglycemia and its risk factors
Jiapei LI ; Weigang ZHAO ; Tao YUAN ; Yong FU ; Yingyue DONG ; Juan LI ; Juntao LIU
Chinese Journal of Clinical Nutrition 2019;27(2):70-75
Objective To explore the long-term outcome of postpartum glucose metabolism among patients with gestational hyperglycemia and its risk factors.Methods Patients with gestational hyperglycemia,diagnosed by 100 g oral glucose tolerance test (OGTT) during 24th to 28th gestation week between 2010 and 2012 and giving the childbirth in Peking Union Medical College Hospital,were included.The glucose metabolism outcomes were evaluated by 75 g OGTT.The risk factors influencing the glucose metabolism outcome and the glucose metabolism parameter changes between the pregnancy term and now were also analyzed.Results Forty patients with gestational hyperglycemia were included.The follow-up time was postpartum 5-8 years and (6.83±0.74) years on average.Among them,3 patients were diagnosed with type 2 diabetes and 9 patients were diagnosed with impaired glucose intolerance.The overall rate of abnormal glucose metabolism was 30 percent.The third-hour glucose of OGTT larger than 7.45 mmol/L and the area under the glucose curve (Glu AUC) during OGTT larger than 24.875 mmol×h/L were the risk factors for the abnormal glucose metabolism outcome,with the odds ratio of 5.769 (95% confidence interval 1.064-31.270,P=0.042) and 12.5 (95% confidence interval 2.226-70.187,P=0.004).Using the 2-hour glucose larger than 8.25 mmol/L and 3-hour glucose larger than 7.45 mmol/L in the OGTT of midtrimester to judge the glucose state in the follow-up visit can achieve the diagnostic efficacy with the sensitivity of 75%,specificity of 82%,positive prediction value of 64% and negative prediction value of 88%.Comparing with now,the fasting glucose in the midtrimester was lower ([5.49±0.43] vs.[4.55±0.47] mmol/L,P<0.001),the fasting insulin in the midtrimester was high-er (12.30 [6.35,16.55] vs.8.31 [6.79,12.00] μIU/ml,P=0.048),HOMA-β in the midtrimester was higher (202.67 [145.71,335.71] vs.85.41 [78.63,112.13],P<0.001).Conclusion The third-hour glucose larger than 7.45 mmol/L and the glucose area under the curve larger than 24.88 mmol×h/L in the OGTT of midtrimester are the risk factors for the abnormal glucose state in the postpartum long-term follow-up.The combination of the second-hour and the third-hour glucoses in the 100 g OGTT of midtrimester can help to predict the postpartum long-term glucose state.

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