Overcoming chemoresistance in non-angiogenic colorectal cancer by metformin via inhibiting endothelial apoptosis and vascular immaturity / 药物分析学报

The development of chemoresistance which results in a poor prognosis often renders current treatments for colorectal cancer(CRC).In this study,we identified reduced microvessel density(MVD)and vascular immaturity resulting from endothelial apoptosis as therapeutic targets for overcoming chemoresistance.We focused on the effect of metformin on MVD,vascular maturity,and endothelial apoptosis of CRCs with a non-angiogenic phenotype,and further investigated its effect in overcoming chemoresistance.In situ transplanted cancer models were established to compare MVD,endothelial apoptosis and vascular maturity,and function in tumors from metformin-and vehicle-treated mice.An in vitro co-culture system was used to observe the effects of metformin on tumor cell-induced endothelial apoptosis.Transcriptome sequencing was performed for genetic screening.Non-angiogenic CRC developed inde-pendently of angiogenesis and was characterized by vascular leakage,immaturity,reduced MVD,and non-hypoxia.This phenomenon had also been observed in human CRC.Furthermore,non-angiogenic CRCs showed a worse response to chemotherapeutic drugs in vivo than in vitro.By suppressing endo-thelial apoptosis,metformin sensitized non-angiogenic CRCs to chemo-drugs via elevation of MVD and improvement of vascular maturity.Further results showed that endothelial apoptosis was induced by tumor cells via activation of caspase signaling,which was abrogated by metformin administration.These findings provide pre-clinical evidence for the involvement of endothelial apoptosis and subsequent vascular immaturity in the chemoresistance of non-angiogenic CRC.By suppressing endothelial apoptosis,metformin restores vascular maturity and function and sensitizes CRC to chemotherapeutic drugs via a vascular mechanism.

Effect of human urinary kallidinogenase on cognitive function of SAMP8 mouse model and its mechanism / 中国药理学通报

Aim To study the effect of human urinary kallidinogenase(HUK)on the cognitive function of SAMP8 mouse model and its mechanism. Methods SAMP8 mice were divided intofive groups:SAMP8 group,treatment group(giving 8.75×10-3,1.75×10-2,3.5×10-2,7.0×10-2 HUK),and the SAMR1 vehicle group was used as blank control. Each group was performed Morris water maze to detect spatial cognition. Afterwards the group with the most obvious cognitive improvement(HUK group)was selected for the follow-up experiments. Immunohistochemical detection of ChAT expression in CA3 area was further verified by RtPCR. Western blot was used to detect the expression of PSD95,SYN,BDNF,and pCREB protein. The activity of MPO and the content of IL-1β and IL-18 were determined. Results The passing times in the SAMP8 group was less than that of the SAMR1 group(P<0.05). The passing times of treatment group increased compared with the SAMP8 group(P<0.05 or P<0.01),and the spatial probe time of the target quadrant was shorter(P<0.05 or P<0.01). We conducted follow-up experiments with group d(HUK group). The expression of ChAT positive cells in CA3 area of SAMP8 group was significantly lower than that of SAMR1 group; the expression of positive cells in HUK group significantly increased; RtPCR showed that ChAT expression in SAMP8 group was lower than that in SAMR1 group,and ChAT expression was significantly higher than that in SAMP8 group after HUK treatment. Compared with the SAMR1 group,the levels of IL-1β,IL-18 and MPO activity in the CA3 area of SAMP8 group significantly increased,and the protein expressions of PSD95,SYN,BNDF and pCREB decreased. After HUK treatment,the content of IL-1β,IL-18 and MPO activity decreased,and the expression of PSD95,SYN,BNDF and pCREB increased. Conclusions HUK can improve the spatial cognition of SAMP8 mice. The mechanism may be achieved by promoting the expression of ChAT in CA3 area,reducing the oxidative stress and increasing synapse-related proteins.

Effects of Dianxianqing granules on tau protein in P301S mice by regulating mitophagy / 中国药房

OBJECTIVE To study the effects of Dianxianqing granules on the tau protein in P301S mice by regulating mitophagy. METHODS Totally 36 P301S mice were randomly divided into model group， Dianxianqing granule group （12.48 g/kg）， donepezil hydrochloride group （positive control， 1.3 mg/kg）， with 12 mice in each group； another 10 C57BL6 mice were selected as control group. Administration groups were given relevant drug solutions intragastrically， and control group and model group were given constant volume of water intragastrically. The gavage volume was 20 mL/kg， once a day， for consecutive 5 months. During the experiment， the general condition of mice was observed in each group. After the last medication， the learning and memory ability was determined by Y maze test and Morris water maze test； HE staining was used to observe the morphological changes in brain tissue， and Nissl staining was used to observe the structure of neural cells and the number of Nissl bodies in cerebral tissue. Immunohistochemistry was used to detect the expressions of phospho-tau serine 202/threonine 205 （abbreviated as AT8） in brain tissue. Western blot assay was used to determine the expressions of mitophagy-associated proteins [PTEN-induced putative kinase-1 （PINK1）， Parkin， microtubule-associated protein 1 light chain 3B （LC3B）， p62]， synaptic-associated proteins [postsynaptic density protein-95 （PSD-95）， synaptophysin （SYP）， and growth-associated protein-43 （GAP-43）] and the phosphorylation of tau protein [expressed by the phosphorylation levels of serine 199 （Ser199） and Ser202] in brain tissue. RESULTS The mice in E-mail：lnzyxyqy2003@163.com model group showed symptoms such as white hair， decreased body mass， and lower limb paralysis， with incomplete hippocampal structures in their brain tissue， as well as incomplete cell membrane edges and cell structures； the spontaneous alternating response rate， the times of crossing platform， the number of Nissl bodies， the protein expressions of PINK1， Parkin， LC3B， SYP， GAP-43， and PSD-95 were decreased significantly， compared with control group； swimming latency （fourth and fifth day）， the protein expressions of AT8 and p62，the phosphorylation levels of Ser199 and Ser202 were increased or lengthened significantly， compared with control group （P＜0.05 or P＜0.01）. Compared with model group， the above symptoms and indexes of mice were improved significantly in administration groups （P＜0.05 or P＜0.01）. CONCLUSIONS Dianxianqing granules can effectively improve cognitive impairment in P301S mice，the mechanism of which may be associated with inducing mitochondrial autophagy， reducing the hyperphosphorylation of tau protein， up-regulating the expression of synaptic-associated proteins in brain tissue，and repairing damaged neural cells.

Hepatitis B virus X protein promotes podocyte pyroptosis in hepatitis B virus-associated glomerulonephritis by down-regulating microRNA -223 targeting NLRP3 inflammasome / 中华肝脏病杂志

Objective: To investigate the potential function and related mechanism of microRNA-223 (miRNA-223) in the podocyte pyroptosis of hepatitis B virus (HBV)-associated glomerulonephritis induced by HBV X protein (HBx). Methods: HBx-overexpressing lentivirus was transfected into human renal podocytes to mimic the pathogenesis of HBV-GN. Real-time fluorescence quantitative PCR and Western blotting experiments were used to detect the mRNA and protein expression of pyroptosis-related proteins [nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3), apoptosis-associated speck-like protein containing a CARD (ASC) and caspase-1], and inflammatory factors (interleukin-1β and interleukin-18), respectively.TUNEL staining and flow cytometry were used to detect the number of pyroptosis cells. Immunofluorescence staining was used to detect the expression of podocytes biomarkers desmin and nephrin; Hoechst 33342 staining was used to observe the morphological and quantitative changes of podocyte nuclei. Enzyme-linked immunosorbent assay was used to measure caspase-1 activity. The dual luciferase reporter gene assay was used to verify the downstream target of miRNA-223. Podocytes were divided into the following nine groups: control group (no special treatment), empty plasmid group (transfected with empty plasmid), HBx overexpression group (transfected with HBx overexpression lentivirus), HBx overexpression+miRNA-223 mimic group (transfected with HBx overexpression lentivirus and miRNA-223 mimic), HBx overexpression+miRNA-223 inhibitor group (transfected with HBx overexpression lentivirus and miRNA-223 inhibitor), HBx overexpression+miRNA-223 mimic+NLRP3 group (transfected with HBx overexpression lentivirus, miRNA-223 mimic and NLRP3 overexpression plasmid), HBx overexpression+miRNA-223 mimic+ NLRP3 siRNA group (transfected with HBx overexpression lentivirus, miRNA-223 mimic and NLRP3 siRNA), HBx overexpression+miRNA-223 inhibitor+NLRP3 group (transfected with HBx overexpression lentivirus, miRNA-223 inhibitor and NLRP3 overexpression plasmid), HBx overexpression+miRNA-223 inhibitor+NLRP3 siRNA group (transfected with HBx overexpression lentivirus, miRNA-223 inhibitor and NLRP3 siRNA). Results: miRNA-223 was down-regulated in HBx overexpression group compared with the control group (P < 0.05). TUNEL and immunofluorescence staining showed that NLRP3 knockdown attenuated podocyte injury and pyroptosis induced by HBx overexpression (P < 0.05). Dual luciferase reporter gene assay demonstrated that NLRP3 was one of the downstream targets of miRNA-223. Rescue experiments revealed that NLRP3 overexpression weakened the protective effect of miRNA-223 in podocyte injury (P < 0.05). The addition of miRNA-223 mimic and NLRP3 siRNA decreased the expression of NLRP3 inflammasome and cytokines, and reduced the number of pyroptosis cells induced by HBx overexpression (all P < 0.05); The addition of miRNA-223 inhibitor and NLRP3 overexpression plasmid significantly increased the expression of NLRP3 inflammasome and cytokines, caspase-1 activity, and the number of pyroptosis cells (all P < 0.05). Conclusion: HBx may promote podocyte pyroptosis of HBV-GN via downregulating miRNA-223 targeting NLRP3 inflammasome, suggesting that miRNA-223 is expected to be a potential target for the treatment of HBV-GN.

Application of partial least squares algorithm to explore bioactive components of crude and stir-baked hawthorn for invigorating spleen and promoting digestion / 中国中药杂志

This study was aimed at identifying the bioactive components of the crude and stir-baked hawthorn for invigorating spleen and promoting digestion, respectively, to clarify the processing mechanism of hawthorn by applying the partial least squares(PLS) algorithm to build the spectrum-effect relationship model. Firstly, different polar fractions of crude and stir-baked hawthorn aqueous extracts and combinations of different fractions were prepared, respectively. Then, the contents of 24 chemical components were determined by ultra-high performance liquid chromatography-mass spectrometry. The effects of different polar fractions of crude hawthorn and stir-baked hawthorn aqueous extracts and combinations of different fractions were evaluated by measuring the gastric emptying rate and small intestinal propulsion rate. Finally, the PLS algorithm was used to establish the spectrum-effect relationship model. The results showed that there were significant differences in the contents of 24 chemical components for different polar fractions of crude and stir-baked hawthorn aqueous extracts and combinations of different fractions, and the gastric emptying rate and small intestinal propulsion rate of model rats were improved by administration of different polar fractions of crude and stir-baked hawthorn aqueous extracts and combinations of different fractions. The bioactive components of crude hawthorn identified by PLS models were vitexin-4″-O-glucoside, vitexin-2″-O-rhamnoside, neochlorogenic acid, rutin, gallic acid, vanillic acid, citric acid, malic acid, quinic acid and fumaric acid, while neochlorogenic acid, cryptochlorogenic acid, rutin, gallic acid, vanillic acid, citric acid, quinic acid and fumaric acid were the bioactive components of stir-baked hawthorn. This study provided data support and scientific basis for identifying the bioactive components of crude and stir-baked hawthorn, and clarifying the processing mechanism of hawthorn.

Interobserver agreement of international classification of myopic maculopathy / 中华眼底病杂志

Objective:To observe the interobserver agreement of classification of macular degeneration in severe pathological myopia (PM) by ophthalmologists with different clinical experience.Methods:A retrospective study. From January 2019 to December 2021, 171 eyes of 102 patients with severe PM macular degeneration who were examined at Eye Center of Beijing Tongren Hospital of Capital Medical University were included in the study. The clinical data such as age, gender, axial length, spherical equivalent power, fundus color photography, and optical coherence tomography (OCT) were collected in detail. Six independent ophthalmologists (A, B, C, D, E, F) classified each fundus photography based on META-PM and ATN classification of atrophy (A) system and interobserver agreement was assessed by Kappa statistics. According to the classification standard of traction (T) in the ATN classification, the OCT images were interpreted and classified, in which T0 was subdivided into retinal pigment epithelium (RPE) and choroidal thinning, choroidal neovascularization (CNV) with partial RPE and choroidal atrophy, RPE, and choroidal atrophy. Lamellar macular hole can't be classified by ATN system, which was defined as TX. Kappa ( κ) test was used to analyze the consistency of classification results between physicians A, B, C, D, E and F. κ value ≤0.4 indicates low consistency, 0.4 < κ value ≤ 0.6 indicates moderate consistency, and κ value >0.6 indicates strong consistency. Results:Among the 171 eyes of 102 cases, there were 20 males with 37 eyes (19.6%, 20/102), and 82 females with 134 eyes (80.4%, 82/102); age was 61.97±8.78 years; axial length was (30.87±1.93) mm; equivalent spherical power was (-16.56±7.00) D. Atrophy (A) classification results in META-PM classification and ATN classification, the consistency of physician A, B, C, D, E and physician F were 73.01%, 77.19%, 81.28%, 81.28%, 88.89%; κ value were 0.472, 0.538, 0.608, 0.610, 0.753, respectively. In the ATN classification, the T0, T1, T2, T3, T4, and T5 were in 109, 18, 11, 12, 9, and 8 eyes, respectively; TX was in 4 eyes.Conclusions:There are differences in the consistency of classification of severe PM macular lesions among physicians with different clinical experience, and the consistency will gradually improve with the accumulation of clinical experience.

Trends in the prevalence of Internet addiction among adolescents from 2004 to 2019 in Shanghai / 中国学校卫生

Objective@#To analyze the trends of Internet addiction among adolescents in Shanghai, so as to provide theoretical evidence for the prevention and control of Internet addiction in adolescents.@*Methods@#A multistage stratified cluster random sampling method was conducted, and 92 171 junior and senior high school students in Shanghai were selected for questionnaire survey in 2004-2019. Evaluation of Internet addiction, loneliness, academic pressure and depression among middle school students.@*Results@#In 2004-2019, the rate of Internet addiction among middle school students in Shanghai was 4.3%, which without significant differences by year( t =1.8, P >0.05). The detection rate of Internet addiction in boys (5.3%) was higher than that in girls (3.4%) ( χ 2=186.8, P <0.01), and was highest in secondary vocational school (7.7%), followed by senior high school (4.6%) and junior middle school students (2.8%) ( χ 2=746.5, P <0.01). The prevalence of Internet addiction in girls, senior high school students, secondary vocational school students, students aged 16-20, students with loneliness or high academic pressure showed an increasing trend in 2004-2019, with the average annual increase rate ( APC ) of 6.62%, 5.45%, 2.13%, 3.36%, 4.09% and 3.60% respectively ( P <0.05).@*Conclusion@#Internet addiction among adolescents in Shanghai showed an increasing trend in some groups from 2004-2019, but without significant differences by year in the overall groups. Comprehensive prevention and control programs are needed for adolescent Internet addiction, especially for those with mental health problems.

Multi-functional osteoclasts in matrix-based tissue engineering bone / 中华创伤杂志(英文版)

The repair of bone defects, especially for the large segment of bone defects, has always been an urgent problem in orthopedic clinic and attracted researchers' attention. Nowadays, the application of tissue engineering bone in the repair of bone defects has become the research hotspot. With the rapid development of tissue engineering, the novel and functional scaffold materials for bone repair have emerged. In this review, we have summarized the multi-functional roles of osteoclasts in bone remodeling. The development of matrix-based tissue engineering bone has laid a theoretical foundation for further investigation about the novel bone regeneration materials which could perform high bioactivity. From the point of view on preserving pre-osteoclasts and targeting mature osteoclasts, this review introduced the novel matrix-based tissue engineering bone based on osteoclasts in the field of bone tissue engineering, which provides a potential direction for the development of novel scaffold materials for the treatment of bone defects.

Improvement effects of Dianxianqing granule on blood-brain barrier injury in Alzheimer ’s disease model mice / 中国药房

OBJECTIVE To study the impr ovement effects of Dianxianqing granule on blood-brain barrier （BBB）injury in Alzheimer’s disease （AD）model mice by regulating NLR family pyrin domain containing 3（NLRP3）inflammasome signaling pathway. METHODS Totally 125 mice were randomly divided into sham operation group （n＝25）and modeling group （n＝100） by body weight. AD model was induced by intracerebroventricular injection of β-amyloid 25-35 in model group. Sham operation group was given normal saline with same method. The 100 model mice were randomly divided into model group ，Donepezil hydrochloride tablets group （positive control 1，1.3 mg/kg，i.g.），MCC950 group [positive control 2（selective NLRP 3 inhibitor），10 mg/kg，i.p.] and Dianxianqing granule group （12.48 g/kg by crude drug ，i.g.）by body weight ，with 25 mice in each group. Second day after modeling ，administration groups were given relevant medicine ，once a day ，for consecutive 21 d. Sham operation group and model group were given intragastric administration of water and intraperitoneal injection of normal saline. At last administration，the learning and memory ability was determined by Y maze test ，and blood-brain barrier permeability was measured by Evans blue leakage assay. The expressions of NLRP 3，anti-ionized calcium-binding adapter molecule 1（IBA-1），nuclear factor kappa B （NF-κB）p65，p53 upregulated modulator of apoptosis （PUMA），occludin（ocln），zonula occluden- 1（ZO-1）and claudin-5 （cldn5） in cerebral tissue were determined. RESULTS Compared with model group ， spontaneous alternate response rate ，protein expressions of ocln ，cldn5 lnzyxyqy2003@163.com and ZO- 1 in cerebral tissue were increased significantly in administration groups （P＜0.05 or P＜0.01）；Evans blue E-mail：jiadg2003@126.com content and protein expressions of NLRP 3，IBA-1，PUMA and NF-κB p65 in cerebral tissue were decreased significantly （P＜0.05 or P＜0.01）. CONCLUSIONS Dianxianqing granule can improve BBB injury of AD model m ice by inhibiting NLRP 3 inflammasome signaling pathway.

Concordant systemic and local eosinophilia relates to poorer disease control in patients with nasal polyps / 中华耳鼻咽喉头颈外科杂志

Objective: To explore whether blood and polyp tissue eosinophil numbers are independent risk factors for poor disease control in patients with nasal polyp. Methods: By using the electronic medical records database and manual evaluation, 183 nasal polyp patients who had undergone endoscopic sinus surgery at least one year prior to the study with complete data of tissue specimens, baseline blood routine test, nasal endoscopy and sinus computed tomography, were identified and recruited to assess disease control based on the criteria of a European Position Paper on Rhinosinusitis and Nasal Polyps 2012 (EPOS 2012). Multiple logistic regression model was used to determine the association between blood and tissue eosinophil numbers and risk of poor disease control by adjusting for demographics and comorbidities. Results: We broke down the cohort into 4 groups according to blood (0.3×109/L) and tissue (10%) eosinophils. The patients without eosinophilic inflammation represented the largest group (41.5%). The group with concordant blood and tissue eosinophilia represented the second largest (31.2%), and the patients with isolated tissue (15.3%) or blood (12.0%) eosinophilia were relatively rare. Multiple logistic regression models found blood eosinophil count and tissue eosinophil percentage were independently associated with increased risk for poor disease control after adjustments for covariates related to poor treatment outcome. Furthermore, subjects with concordant blood and tissue eosinophilia had a higher risk for poor disease control than those with isolated blood or tissue eosinophilia. Conclusion: Concordant blood and tissue eosinophilia relates to a higher likelihood of poor disease control than isolated blood or tissue eosinophilia after adjustment of potential confounders in nasal polyp patients.

Association between cumulative blood pressure and long-term risk of cardiovascular disease: findings from the 26-year Chinese Multi-provincial Cohort Study-Beijing Project / 中华医学杂志(英文版)

BACKGROUND@#Cumulative blood pressure (BP), a measure incorporating the level and duration of BP exposure, is associated with the risk of cardiovascular disease (CVD). However, the level at which cumulative BP could significantly increase the risk remains unclear. This study aimed to investigate the association of 15-year cumulative BP levels with the long-term risk of CVD, and to examine whether the association is independent of BP levels at one examination.@*METHODS@#Data from a 26-year follow-up of the Chinese Multi-provincial Cohort Study-Beijing Project were analyzed. Cumulative BP levels between 1992 and 2007 were calculated among 2429 participants free of CVD in 2007. Cardiovascular events (including coronary heart disease and stroke) occurring from 2007 to 2018 were registered. Adjusted hazard ratios (HRs) for CVD incidence associated with quartiles of cumulative systolic blood pressure (SBP) and diastolic blood pressure (DBP) were calculated.@*RESULTS@#Of the 2429 participants, 42.9% (1042) were men, and the mean age in 2007 was 62.1 ± 7.9 years. Totally, 207 CVD events occurred during the follow-up from 2007 to 2018. Participants with higher levels of cumulative SBP or DBP exhibited a higher incidence rate of CVD (P < 0.001). Compared with the lowest quartile of cumulative SBP, the HR for CVD was 1.03 (95% confidence interval [CI]: 0.59-1.81), 1.69 (95% CI: 0.99-2.87), and 2.20 (95% CI: 1.21-3.98) for the second to the fourth quartile of cumulative SBP, and 1.46 (95% CI: 0.86-2.48), 1.99 (95% CI: 1.18-3.35), and 2.08 (95% CI: 1.17-3.71) for the second to the fourth quartile of cumulative DBP, respectively. In further cross-combined group analyses with BP measurements in 2007, 15-year cumulative BP levels higher than the median, that is, 1970.8/1239.9 mmHg·year for cumulative SBP/DBP, which were equivalent to maintaining SBP/DBP levels of 131/83 mmHg or above on average in 15 years, were associated with higher risk of CVD in subsequent years independent of BP measurements at one-time point.@*CONCLUSION@#Cumulative exposure to moderate elevation of BP is independently associated with increased future cardiovascular risk.

Effect of Functional Electrical Stimulation on Upper-limb Function in Stroke Patients with Hemiplegia: A Meta-analysis / 中国康复理论与实践

Objective:To investigate the effect of functional electrical stimulation on upper-limb function in stroke patients with hemiplegia. Methods:Randomized controlled trials about functional electrical stimulation on upper-limb function in stroke patients with hemiplegia were recalled from databases of PubMed, EMBASE, Web of Science, Cochrane, CNKI, Wanfang data, CBM and VIP. The quality of the trials was evaluated and the data were extracted. Data were analyzed with RevMan 5.3. Results:A total of 13 trials involving 744 patients were included. Functional electrical stimulation group could improve upper-limb motor function more compared with routine rehabilitation group (MD = 9.77, 95%CI 6.36 to 13.17,P < 0.001), whatever less than 30 minutes a time (MD = 9.78, 95%CI 6.26 to 13.29,P < 0.001) or more than 45 minutes a time (MD = 14.20, 95%CI 0.99 to 27.40,P < 0.05), for less than four weeks (MD = 5.82, 95%CI 2.58 to 9.06,P < 0.001) or more (MD = 13.42, 95%CI 8.43 to 18.41,P < 0.001). Functional electrical stimulation group also improved the activities of daily living for stroke patients (MD = 13.72, 95%CI 11.60 to 15.84,P < 0.001). Conclusion:Functional electrical stimulation is effective on upper-limb motor function and activities of daily living for stroke patients with hemiplegia, which could be widely applied in clinic.

Effects of keto acid supplements on Chinese patients receiving maintenance hemodialysis: a prospective, randomized, controlled, single-center clinical study / 中华医学杂志(英文版)

BACKGROUND@#The effects of keto acid (KA) supplements on Chinese patients receiving maintenance hemodialysis (MHD) are unclear. This study aimed to evaluate the effects of KA supplementation on nutritional status, inflammatory markers, and bioelectric impedance analysis (BIA) parameters in a cohort of Chinese patients with MHD without malnutrition.@*METHODS@#This was a prospective, randomized, controlled, single-center clinical study conducted in 2011 till 2014. Twenty-nine patients with MHD were randomly assigned to a control (n = 14) or a KA (n = 15) group. The control group maintained a dietary protein intake of 0.9 g/kg/day. The KA group received additional KA supplement (0.1 g/kg/day). BIA was used to determine the lean tissue mass, adipose tissue mass, and body cell mass. The patients' nutritional status, dialysis adequacy, and biochemical parameters were assessed at the ends of the third and sixth months with t test or Wilcoxon rank-sum test.@*RESULTS@#The daily total energy intake for both groups was about 28 kcal/kg/day. After 6 months, the Kt/V (where K is the dialyzer clearance of urea, t is the dialysis time, and V is the volume of the distribution of urea) was 1.33 ± 0.25 in KA group, and 1.34 ± 0.25 in the control group. The median triceps skin-fold thickness in KA group was 12.00 and 9.00 mm in the control group. In addition, the median hand-grip strength in KA group was 21.10 and 25.65 kg in the control group. There were no significant differences between the groups with respect to the anthropometry parameters, dialysis adequacy, serum calcium and phosphorus levels, inflammatory markers, and amino-acid profiles, or in relation to the parameters determined by BIA. Both groups achieved dialysis adequacy and maintained nutritional status during the study.@*CONCLUSIONS@#In this cohort of Chinese patients with MHD, the patients in the control group whose dietary protein intake was 0.9 g/kg/day and total energy intake was 28 kcal/kg/day, maintained well nutritional status during study period. The KA supplement (0.1 g/kg/day) did not improve the essential amino acid/non-essential amino acid ratio, nor did it change the patients' mineral metabolism, inflammatory parameters, or body compositions.

New progress on transforming growth factor β in ocular fibroproliferative diseases / 国际眼科杂志(Guoji Yanke Zazhi)

@#Fibrotic disease can disrupt the normally transparent ocular tissues resulting in irreversible loss of vision. A common feature in fibrotic eye disease is the transdifferentiation of cells into myofibroblasts that can occur through a process known as epithelial-mesenchymal transition. Transforming growth factor β has a central role in fibrogenesis by modulating the fibroblast function, inducing myofibroblast transdifferentiation and promoting extracellular matrix accumulation. It has been implicated in numerous fibrotic eye diseases. This article aims to introduce the new progression on TGFβ and fibrotic ocular diseases and its clinical significance for providing the reference in clinical practices.

Application and safety of bupivacaine undergoing tumescent liposuction in general anesthesia / 中华医学美学美容杂志

Objective To explore the safety,composition and effectiveness of bupivacaine in swelling fluid and to understand the safe use of the swelling fluids contained bupivacaine as local anesthetics in liposuction.Methods The liposuction was completed in 149 patients,aged 18-63 years with the swelling fluid contained bupivacaine in different proportions by negative pressure liposuction for exploring the method and safe use of the swelling fluid contained bupivacaine in general anesthesia.Results The dose range of bupivacaine at 1.14-1.87 mg/kg did not show toxicity.Bupivacaine combined with lidocaine as a part of swelling fluid was suitable for all range of liposuction in general anesthesia.There was no pain sensation first day after the operation.The pain was obvious on the day after surgery in lidocaine group.The advantage using bupivacaine as swelling fluid was that the postoperative recovery was fast,the healing was good,and the complications were few.Conclusions Bupivacaine as the main anesthetic agent for swelling fluid shows the advantages of long analgesic effect,good anesthetic effect,and no pain after operation.It is worth further application.

Study on the Improvement Effects and Mechanism of Leontopodium leontopodioides Combined with Astragalus membranaceus on Renal Function of MsPGN Model Rats / 中国药房

OBJECTIVE：To study the improvement effect and possible mechanism of Leontopodium leontopodioides combined with Astragalus membranaceus on the renal function of mesangial proliferative glomerulonephritis （MsPGN） model rats. METHODS：Totally 85 rats were randomly divided into sham operation group （n＝10）and modeling group （n＝75）. Sham operation group underwent sham operation ，and MsPGN model was induced by immunological method [Freund ’s adjuvant+BSA + lipopolysaccharide（LPS）] in modeling group. After successfully modeling ，70 rats were randomly divided into model group ，L. leontopodioides+A. membranaceus high-dose，medium-dose and low-dose groups （4.05，2.03，1.02 g/kg，by total crude drug ），L. leontopodioides alone group （2.70 g/kg，by crude drug ），Tripterygium glycosides tablet group （positive control 1，0.02 g/kg）， Lotensin tablet group （positive control 2，0.02 g/kg），with 10 rats in each group. Sham operation group and model group were given constant volume of normal saline intragastrically ； administration groups were given relevant drug solution intrasgastrcially at a volume of 15 mL/kg，once a day ，for consecutive 5 weeks. At last administration ，24 h urinary lnzyxyqy2003@163.com protein，urine creatinine and serum creatinine were determined in rats. The right kidney was weighed ，and HE staining was used to observe the pathomorpholog y changes of renal tissue. Immunohistochemistry was used to detect the protein expression of NF-κB p65 in renal tissue. Western blotting assay was used to determine the protein expressions of NF-κB p65，IκBα，ERK，p-ERK and p 38 MAPK in renal tissue. RESULTS ：Compared with sham operation group ，right kidney weight ，24 h urine protein and serum creatinine levels ，protein expressions of NF-κB p65， p-ERK and p 38 MAPK in renal tissue were increased significantly in model group （P＜0.05 or P＜0.01）；the level of urine creatinine and protein expression of IκBα in renal tissue were decreased significantly（P＜0.05 or P＜0.01）；there were obvious glomerular hypertrophy ，diffuse increase of mesangial cells ，necrosis of renal tubules and other pathomorphological changes in renal tissue. Compared with model group ，right kidney weight and serum creatinine level were decreased significantly in L. leontopodioides alone group （P＜0.05），while urine creatinine level was increased significantly （P＜0.05），but there was no statistical significance in the level of 24 h urine protein （P＞0.05）；the right kidney weight ，24 h urine protein ，serum creatinine level and protein expression levels of NF-κB p65，p-ERK and p38 MAPK in renal tissue were decreased significantly in L. leontopodioides+A. membranaceus high-dose group （P＜0.05），while the urine creatinine level and protein expression level of IκBα in renal tissue were increased significantly （P＜0.05 or P＜0.01）；there was no statistical significance in above indexes in L. leontopodioides+A. membranaceus medium-dose，low-dose groups （P＞0.05）；pathological changes of renal tissue were improved to different extents in administration groups ，especially in L. leontopodioides +A. membranaceus high-dose group. CONCLUSIONS ： High dose of L. leontopodioides +A. membranaceus can improve renal function of MsPGN model rats by inhibiting MAPK/NF-κB signal pathway.

The association between plasma levels of 20 amino acids and risk of diabetes / 中华内科杂志

Objective To investigate the association between the plasma levels of 20 amino acids and the risk of diabetes in middle-aged and elderly population.Methods This study was a part of the Chinese multi-provincial cohort study conducted in communities of Shougang.In 2007 and 2012,the population was investigated for diabetes and other risk factors.Blood samples collected from 475 people were tested for various amino acid levels by liquid chromatography-tandem mass spectrometry.A multivariate logistic regression analysis was used to analyze the association between plasma amino acid levels and diabetes risk.Results The age of the selected population at baseline was (58.7±6.3) years,and the blood glucose level at baseline was (5.68 ± 1.34) mmol/L.Among them,56 (11.79％) subjects were diabetes.Multivariate logistic regression analyses showed that after adjusting for age,gender,body mass index,systolic blood pressure and dyslipidemia,individuals with plasma branched-chain amino acid (valine,leucine and isoleucine) and cysteine in the highest tertile levels were at high risk of diabetes with the ORs of 3.61 (95％ CI 1.48-8.80),3.27 (95％ CI 1.34-7.99),2.46 (95％ CI 1.04-5.84) and 2.09 (95％ CI 1.02-4.27),respectively.After 5 years' followed up,5.73％ (24/419) subjects developed diabetes.Compared with those in the lowest tertile,individuals with plasma branched-chain amino acid (total concentration),phenylalanine,and tyrosine levels at baseline in the highest tertile had 3.69 times,3.61 times and 4.14 times higher risk to develop new diabetes,respectively.In contrast,individuals with plasma glycine level in the highest tertile had only 76％ (OR 0.24,95％ CI 0.06-0.91) risk for the development of diabetes compared with those with plasma glycine level in the lowest tertile.Conclusions The increase in plasma branched-chain amino acid and cysteine levels is significantly associated with an increase in incident diabetes.Subjects with higher levels of branched-chain amino acids and aromatic amino acids (phenylalanine,tyrosine) had a significantly higher risk of developing new-onset diabetes,while those with higher glycine levels had a significantly lower risk of developing diabetes in 5 years.

Self?management of blood pressure among elderly hypertensive patients in new rural communities of Shanghai / 中华健康管理学杂志

Objective To investigate the status of self‐management of blood pressure (BP) among elderly hypertensive patients living in new rural communities of Shanghai. Methods We enrolled a total of 2 241 hypertensive patients over 60 years old who participated in the National Key Research and Development Project "Cohort study on hypertension" of the 13th Five‐Year Plan in Langxia, Shanghai from May to July 2018. Questionnaires, physical examinations, and laboratory tests were conducted. We collected participants' demographic information, cardiovascular history, and self‐management behaviors related to hypertension. The status of self‐management of BP among participants with hypertension was analyzed. Pearson's chi‐squared test was used to explore the differences between males and females. Results Participants'mean age was (70.0±6.8) years, and males accounted for 38.8% of all participants. The systolic and diastolic BP levels of participants were (147.8±15.4) mmHg (1 mmHg=0.133 kPa) and (82.8±9.8) mmHg, respectively. The systolic blood pressure level of women was higher than that of men, and the diastolic blood pressure level of men was higher; the difference was statistically significant (all P<0.05). The awareness, treatment, and control rate of hypertension were 79.0%, 78.0%, and 25.6%, respectively. Males had a significantly higher control rate than females (P<0.05). The status of self‐management of blood pressure was as follows: (1) As to lifestyle, 84.4% of participants lacked exercise, and 69.2% were overweight or obese. The prevalence of smoking and drinking was higher in males (40.7% and 46.2%, respectively), and the proportion of females (12.4%) with anxiety and/or depression was higher than that of males (P all<0.001). (2) Concerning BP‐monitoring, only 10.1% of participants measured BP every week, 22.9% had BP measurement instruments at home, and 4.6% recorded their BP levels. There was no significant difference in self‐blood pressure monitoring behavior between men and women. (3) Regarding adherence to medication treatment, 97.6% took antihypertensive drugs regularly, and 21.6% were on combination therapy. The proportion of men taking combined drugs was higher than that of women, but there was no significant difference. Conclusions The rates of awareness, treatment, and control of hypertension in elderly hypertensive patients in new rural communities of Shanghai were above the national average. However, the status of self‐management of BP was still not satisfactory. More attention should be paid to healthy lifestyle, home BP monitoring, and effective pharmaceutical treatment strategies for hypertension.

Analysis of malaria cases in Haidian District of Beijing from 2005 to 2017 / 中华疾病控制杂志

Objective To understand the epidemiological character of malaria in Haidian District of Beijing from 2005 to 2017. Methods The epidemiological data of malaria was collected from the infectious disease reporting system of medical institutions at various levels in Haidian District of Beijing from 2005 to 2017, and the epidemiological methods was used to analyze the distribution of malaria in population, time and region. Results From 2005 to 2017, 111 malaria cases were reported in Haidian District of Beijing, the annual average incidence rate was 0.26/100 000 and one death case was reported in 2014. Among the four reported types of falciparum malaria, vivax malaria, three-day malaria and untyped malaria, the most common falciparum malaria (54.5%, 60/111), no mixed infection; The peak incidence was concentrated in the summer and autumn of June-September (52.0%, 58/111); the cases were mainly occurred in young adults aged from 20 to 59(93.7%,104/111), and the incidence of males was higher than that of females ( 2=52.9, P<0.001); Cadres were the main ward population (33.3%, 33/111). Malaria cases were reported in 26 streets and towns in Haidian District. 81 cases were imported from abroad, accounting for 71.4% of the total cases, of which 74 (91.36%) were originated from Africa. Conclusions In the past 13 years, the incidence of malaria was sporadic, mainly in imported cases. The monitoring of malaria should be strengthened by entry and exit to prevent the second-generation cases of malaria.

Effectiveness of semi-open suturation of vaginal stump in prevent the development of pelvic lymphocele after pelvic lymphadenectomy / 中国实用妇科与产科杂志

OBJECTIVE: To evaluate the effectiveness of semi-open suturation of vaginal stump in preventing pelvic lym-phocele after pelvic lymphadenectomy during gynecologic cancer surgery.METHODS:This study is a retrospectivestudy.Totally 348 patients with cervic cancer or endometrial cancer who underwent pelvic lymphadenectomy and/or para-aortic lymphadenectomy from January 2012 to September 2018 were divided into two groups according to the suturationof vaginal stump:102 patients were in the semi-open group and 246 patients were in the closed group.The two groupswere compared concerning the surgery time,harvested lymph node,drainage time,albumin level,hemoglobin content,and the incidence of lymphocele and symptomatic lymphocele.RESULTS:There were no differences between two groupswith respect to surgery time,harvested lymph node,drainage time,albumin level or hemoglobin content(P>0.05).Theincidence of lymphocele and symptomatic lyphocele in semi-open group was significantly lower than that in closed group(35.3%versus79.3%,3.9%versus19.5%,P<0.05);the average diameter of lymphocele in semi-open group was also sig-nificantly lower than that in closed group(4.1cm versus 5.9cm,P<0.05).CONCLUSION:The result of this study indicatesthat the application of semi-open saturation of vaginal stump is an effective way to reduce the incidence of pelvic lym-phocele after gynecologic malignancy,which is simple and with reliable effect.It doesn′t increase the incidence of postop-eration complications and deserves clinical application.