Development of a CLDN18.2-targeting immuno-PET probe for non-invasive imaging in gastrointestinal tumors / 药物分析学报

Claudin18.2(CLDN18.2)is a tight junction protein that is overexpressed in a variety of solid tumors such as gastrointestinal cancer and oesophageal cancer.It has been identified as a promising target and a potential biomarker to diagnose tumor,evaluate efficacy,and determine patient prognosis.TST001 is a recombinant humanized CLDN18.2 antibody that selectively binds to the extracellular loop of human Claudin18.2.In this study,we constructed a solid target radionuclide zirconium-89(89Zr)labled-TST001 to detect the expression of in the human stomach cancer BGC823CLDN18.2 cell lines.The[89Zr]Zr-des-ferrioxamine(DFO)-TST001 showed high radiochemical purity(RCP,＞99％)and specific activity(24.15±1.34 GBq/μmol),and was stable in 5％human serum albumin,and phosphate buffer saline(＞85％RCP at 96 h).The EC50 values of TST001 and DFO-TST001 were as high as 0.413±0.055 and 0.361±0.058 nM(P＞0.05),respectively.The radiotracer had a significantly higher average standard uptake values in CLDN18.2-positive tumors than in CLDN18.2-negative tumors(1.11±0.02 vs.0.49±0.03,P=0.0016)2 days post injection(p.i.).BGC823CLDN18.2 mice models showed high tumor/muscle ratios 96 h p.i.with[89Zr]Zr-DFO-TST001 was much higher than those of the other imaging groups.Immunohistochemistry results showed that BGC823CLDN18.2 tumors were highly positive(+++)for CLDN18.2,while those in the BGC823 group did not express CLDN18.2(-).The results of ex vivo biodistribution studies showed that there was a higher distribution in the BGC823CLDN18.2 tumor bearing mice(2.05±0.16％ID/g)than BGC823 mice(0.69±0.02％ID/g)and blocking group(0.72±0.02％ID/g).A dosimetry estimation study showed that the effective dose of[89Zr]Zr-DFO-TST001 was 0.0705 mSv/MBq,which is within the range of acceptable doses for nuclear medicine research.Taken together,these re-sults suggest that Good Manufacturing Practices produced by this immuno-positron emission tomog-raphy probe can detect CLDN18.2-overexpressing tumors.

Advances on pathogenesis of acquired peritoneal ultrafiltration failure in peritoneal dialysis / 中华肝脏病杂志

Peritoneal ultrafiltration failure is a common reason for peritoneal dialysis (PD) withdrawal as well as mortality in PD patients. Based on the three-pore system, inter-cellular small pores and trans-cellular ultra-small pores (aquaporin-1) are mainly responsible for water transfer across the peritoneum. Both small and ultra-small pores-dependent water (free water) transport decline accompanied with time on PD, with more significant decrease in free water, resulting in peritoneal ultrafiltration failure. The reduction of free water transport is associated with fast peritoneal solute transfer, reduced crystalloid osmotic gradient due to increased interstitial glucose absorption, and declined osmotic conductance to glucose resulted from impaired aquaporin-1 function and peritoneal interstitial fibrosis. The decline of small pore-based water is mainly because of fast loss of crystalloid osmotic gradient, decrease of hydrostatic pressure mediated by peritoneal vasculopathy, as well as reduced absolute number of small pores. The current review discusses the advance on pathogenesis of acquired peritoneal ultrafiltration failure in long-term PD.

Analysis of the curative effect of triple surgery under endoscope in the treatment of intractable heel pain / 中国骨伤

OBJECTIVE@#To investigate the clinical effect the treatment of arthroscopy-assisted calcaneal spur resection combined with plantar fascia release and calcaneal decompression in the treatment of the patients with intractable calcaneal pain.@*METHODS@#The clinical data of 50 patients with intractable heel pain from January 2016 to January 2019 were retrospectively analyzed, including 20 males and 30 females;aged from 40 to 68 years old with an average of (50.12±7.35)years old, the medical history ranged from 1 to 4 years. All patients underwent arthroscopy-assisted calcaneal spur resection combined with plantar fascia release and calcaneal decompression, and were followed up, the duration ranged from 24 to 60 months with an average of(42.00±3.28) months. All patients had obvious heel pain before surgery, and X-ray examinations often showed the presence of calcaneal spurs. In addition to the routine foot examination, the changes in the height and angle of the arch of the foot were also measured pre and post-operatively by X-ray, for the evaluation of clinical effect. The VAS system was used to evaluate the degree of foot pain;the AOFAS scoring system was used to comprehensively evaluate the foot pain, voluntary movement, gait and stability.@*RESULTS@#The VAS decreased from (8.75±1.24) before surgery to (5.15±2.35) at 3 months after surgery, (4.07±2.53) at 6 months after surgery, and (3.95±2.44) at the last fllow-up(P<0.05). The AOFAS score increased from (53.46±4.17) before surgery to(92.46±2.53) at 3 months after surgery, (96.33±2.46) at 6 months after surgery, and (97.05±2.37) at the last follow-up(P<0.05). The arch height was (41.54±1.15) mm before operation and (41.49±1.09) mm after the operation, the difference was not statistically significant(P>0.05). The internal arch angle of the foot arch was (121±6)° before operation and (122±7)° after operation. The difference was not statistically significant(P>0.05).@*CONCLUSION@#Arthroscopy-assisted calcaneal bone spurs resection combined with plantar fascia release and calcaneal decompression exhibited great clinical effect for treating intractable heel.

Protective Mechanism of Total Flavonoids of Lavender Against Skin Photoaging in Mice / 中国实验方剂学杂志

ObjectiveTo study the protective effect of total flavonoids of lavender on skin photoaging induced by ultraviolet B （UVB） in mice and to explore its mechanism from the perspective of nuclear factor E2-related factor 2 （Nrf2） antioxidant pathway. MethodEighty-four female KM mice were randomly divided into seven groups， namely blank group， model group， solvent group， vitamin E （0.013 g·kg-1） group， as well as low-， middle-， and high-dose （0.25， 1.25， 2.50 g·kg-1） groups of total flavonoids of lavender. The naked skin on the back of mice was irradiated with UVB for inducing optical damage. Thirty minutes before irradiation， the skin was coated with the total flavonoids of lavender. After continuous irradiation for one week， the skin moisture and elasticity on the back of mice were evaluated， and the effects of total flavonoids of lavender on histopathological changes in mouse skin were investigated by hematoxylin-eosin （HE） and Van Gieson （VG） staining. The levels of malondialdehyde （MDA）， superoxide dismutase （SOD）， total antioxidant capacity （T-AOC）， nitric oxide synthase （NOS）， and glutathione peroxidase （GSH-Px） after skin homogenization were detected by colorimetry， the inflammatory factors interleukin-1 （IL-1）， interleukin-6 （IL-6） and tumor necrosis factor-α （TNF-α） in skin tissue by enzyme-linked immunosorbent assay （ELISA）， and the mRNA expression levels of Nrf2， Kelch-like epichlorohydrin-associated protein 1 （Keap1）， BTB-CNC homology 1 （Bach1）， heme oxygenase-1 （HO-1）， quinone oxidoreductase 1 （NQO1）， and glutamate-cysteine ligase catalytic subunit （GCLC） by real-time polymerase chain reaction （Real-time PCR）. ResultCompared with the blank group， the model group exhibited significantly increased appearance score （P<0.01）， reduced skin moisture and elasticity （P<0.01）， pronounced pathological changes in the skin tissue like epidermal thickening， scabbing， small abscess， and severe injury， elevated MDA， NOS， IL-1， IL-6 and TNF-α （P<0.05， P<0.01）， lowered SOD， T-AOC， Nrf2， Keap1， NQO1 and GCLC mRNA expression （P<0.05，P<0.01）， and up-regulated Bach1 mRNA expression （P<0.01）. Compared with the model group， the total flavonoids of lavender at the low， middle， and high doses all remarkably reduced the appearance score （P<0.01）， enhanced the skin moisture and elasticity （P<0.01）， diminished the MDA， NOS， IL-1， IL-6， and TNF-α （P<0.05， P<0.01）， increased SOD， T-AOC， Nrf2， Keap1， NQO1， HO-1 and GCLC mRNA expression （P<0.05， P<0.01）， and down-regulated the expression of Bach1 mRNA （P<0.01）. ConclusionThe protective effect of the total flavonoids of lavender against skin photoaging in mice is significant， which may be related to its activation of Keap1/Nrf2/ARE signaling pathway， regulation of oxidative stress， and improvement of inflammatory response.

Protective Mechanism of Lavender Against Skin Photodamage Based on Network Pharmacology and Experimental Verification / 中国实验方剂学杂志

ObjectiveTo predict the active ingredients and mechanism of action of lavender in protecting skin photodamage based on network pharmacology and molecular docking technology，and further verify possible signal pathways via animal experiments. MethodThe active ingredients and potential targets of lavender were obtained by SwissTargetPrediction，PharmMapper， and literature. Skin photodamage-related targets were searched from GeneCards，Online Mendelian Inheritance in Man （OMIM），DrugBank and DisGeNET databases. After common targets of the two were screened out，STRING was adopted to analyze the protein-protein interaction （PPI） network，where topological analysis and core target screening were performed by CytoNCA plug-in of Cytoscape 3.8.2. Based on DAVID， gene ontology （GO） annotations and Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway enrichment analysis were carried out among the intersection targets， and the active ingredients of lavender and the signal pathway proteins were selected and verified via molecular docking with AutoDock vina 1.1.2. Finally， mouse photodamage model was established by UVB irradiating the bare skin of mouse back， and the skin condition was observed by naked eyes. Hematoxylin-eosin （HE） and picric acid-acid fuchsin staining （Van Gieson， VG） were used to observe the pathological changes of mouse skin tissues. Western blot was employed to detect the protein expression in mouse skin tissues to further validate the key signal pathways. ResultIn this study，6 active ingredients of lavender，526 potential targets，2 688 disease-related targets，and 258 intersection targets were screened out， and 16 core targets were obtained by PPI network. Additionally， 113 related signal pathways were obtained by KEGG pathway analysis，among which phosphatidylinositol 3-kinase/protein kinase B （PI3K/Akt） pathway and nuclear transcription factor-κB （NF-κB） signal pathway might play a key role in skin photodamage protection by lavender. Molecular docking showed that the active ingredients and the signal pathway proteins were well docked. Animal experiments indicated that the total flavonoids of lavender improved the appearance and histopathological condition of mouse skin， reduced the relative expression levels of phosphorylated（p）-PI3K，p-Akt，and B cell lymphoma 2 （Bcl-2） proteins （P<0.05，P<0.01）， and increased relative expression level of Bcl-2-associated X protein（Bax） （P<0.05）. ConclusionLavender exerts synergistic effect in resisting skin photodamage，with the characteristics of multi-components，multi-targets，and multi-pathways， which provides a basis for subsequent in-depth research on the complex mechanism of lavender against skin photodamage.

Clinical significance of the deep learning algorithm based on contrast-enhanced CT in the differential diagnosis of gastric gastrointestinal stromal tumors with a diameter ≤ 5 cm / 中华胃肠外科杂志

Objective: Contrast-enhanced CT is an important method of preoperative diagnosis and evaluation for the malignant potential of gastric submucosal tumor (SMT). It has a high diagnostic accuracy rate in differentiating gastric gastrointestinal stromal tumor (GIST) with a diameter greater than 5 cm from gastric benign SMT. This study aimed to use deep learning algorithms to establish a diagnosis model (GISTNet) based on contrast-enhanced CT and evaluate its diagnostic value in distinguishing gastric GIST with a diameter ≤ 5 cm and other gastric SMT before surgery. Methods: A diagnostic test study was carried out. Clinicopathological data of 181 patients undergoing resection with postoperative pathological diagnosis of gastric SMT with a diameter ≤ 5 cm at Department of Gastrointestinal Surgery of Renji Hospital from September 2016 to April 2021 were retrospectively collected. After excluding 13 patients without preoperative CT or with poor CT imaging quality, a total of 168 patients were enrolled in this study, of whom, 107 were GIST while 61 were benign SMT (non-GIST), including 27 leiomyomas, 24 schwannomas, 6 heterotopic pancreas and 4 lipomas. Inclusion criteria were as follows: (1) gastric SMT was diagnosed by contrast-enhanced CT before surgery; (2) preoperative gastroscopic examination and biopsy showed no abnormal cells; (3) complete clinical and pathological data. Exclusion criteria were as follows: (1) patients received anti-tumor therapy before surgery; (2) without preoperative CT or with poor CT imaging quality due to any reason; (3) except GIST, other gastric malignant tumors were pathologically diagnosed after surgery. Based on the hold-out method, 148 patients were randomly selected as the training set and 20 patients as the test set of the GISTNet diagnosis model. After the GISTNet model was established, 5 indicators were used for evaluation in the test set, including sensitivity, specificity, positive predictive value, negative predictive value and the area under the receiver operating curve (AUC). Then GISTNet diagnosis model was compared with the GIST-risk scoring model based on traditional CT features. Besides, in order to compare the accuracy of the GISTNet diagnosis model and the imaging doctors in the diagnosis of gastric SMT imaging, 3 radiologists with 3, 9 and 19 years of work experience, respectively, blinded to clinical and pathological information, tested and judged the samples. The accuracy rate between the three doctors and the GISTNet model was compared. Results: The GISTNet model yielded an AUC of 0.900 (95% CI: 0.827-0.973) in the test set. When the threshold value was 0.345, the sensitivity specificity, positive and negative predictive values of the GISTNet diagnosis model was 100%, 67%, 75% and 100%, respectively. The accuracy rate of the GISTNet diagnosis model was better than that of the GIST-risk model and the manual readings from two radiologists with 3 years and 9 years of work experience (83% vs. 75%, 60%, 65%), and was close to the manual reading of the radiologist with 19 years of work experience (83% vs. 80%). Conclusion: The deep learning algorithm based on contrast-enhanced CT has favorable and reliable diagnostic accuracy in distinguishing gastric GIST with a diameter ≤ 5 cm and other gastric SMT before operation.

Chemical constituents of triterpenoids from Euphorbia resinifera / 中国中药杂志

The combination of normal-phase silica gel column chromatography, octadecyl silica(ODS) column chromatography, semi-preparative high performance liquid chromatography(HPLC), etc. was employed to isolate and purify the chemical components from Euphorbia resinifera, and 7 triterpenoids were separated from the ethanol extract of the medicinal materials. Their structures were identified by various spectroscopy methods as cycloartan-1,24-diene-3-one(1), cycloartan-1,24-diene-3-ol(2), 3β-hydroxy-lanosta-8,24-diene-11-one(3), lnonotusane C(4), eupha-8,24-diene-3β-ol-7,11-dione(5), eupha-24-methylene-8-ene-3β-ol-7,11-dione(6), and eupha-8,24-diene-3β,11β-diol-7-one(7). Compounds 1 and 2 are new compounds, and compound 3 is obtained from nature for the first time.

Effect of Huoxue Jiedu Runzao Prescription on Expression of Apoptosis Inhibitor Survivin in Submandibular Gland Cells of Sjögren's Syndrome Mice / 中国实验方剂学杂志

Objective:To investigate the effect of Huoxue Jiedu Runzao prescription on the morphology， apoptosis， and function of submandibular gland in the mouse model of Sjögren's syndrome （SS） and its functioning mechanism， we analyzed the expression of the apoptosis inhibitor Survivin in the submandibular gland cells of SS mice. Method:Female BALB/c57 mice were selected as the normal group. The naive non-obese diabetic （NOD/Ltj） female mice were selected as the SS model， which were randomly assigned into the model group， Paeoniae Radix Alba total glucosides capsule （0.234 g·kg^-1） group， and low-， medium-， and high-dose （15.6， 31.2， 62.4 g·kg^-1， respectively） Huoxue Jiedu Runzao prescription groups. Each group had 15 mice. The morphological and functional changes of submandibular gland and the Survivin expression were observed and measured after 8 weeks of drug intervention. Survivin expression was determined by immunohistochemistry （IHC）， Western blot， and reverse transcription-polymerase chain reaction （RT-PCR）. Result:Compared with normal group， salivary flow and submandibular gland index in model group were significantly decreased （<italic>P</italic><0.01）， and histopathological score of submandibular gland was significantly increased （<italic>P</italic><0.01）. Western blot showed that Survivin protein expression was significantly decreased （<italic>P</italic><0.05）. IHC showed that， Survivin mRNA expression was significantly decreased （<italic>P</italic><0.01）， and RT-PCR results showed that Survivin mRNA expression was significantly decreased （<italic>P</italic><0.01）. Compared with model group， salivary flow and submandibular gland index of mice in Huoxue Jiudu Runzao prescription groups and Paeoniae Radix Alba total glucosides capsules groups were significantly increased （<italic>P</italic><0.05）， histopathological score of submandibular gland was significantly decreased （<italic>P</italic><0.05）， IHC results showed that Survivin expression was significantly increased （<italic>P</italic><0.01）. Western blot and RT-PCR results showed that Survivin protein and mRNA expression of Huoxue Jiudu Runzao prescription high-dose group and Paeoniae Radix Alba total glucosides capsule group were significantly increased （<italic>P</italic><0.05）. Conclusion:Huoxue Jiedu Runzao prescription can improve the secretion function of submandibular acinus， increase the submandibular gland index， and saliva secretion of SS mice by up-regulating survivin in submandibular gland cells of SS mice.

Construction of Salviae Miltiorrhizae Radix et Rhizoma-polydopamine nanoparticles and its protective effect on oxidative damage in cardiomyocytes induced by H2O2 / 中草药

Objective: Using polydopamine (PDA) as a carrier to construct a Salviae Miltiorrhizae Radix et Rhizoma (SMRR) nano-delivery system (PDA-SMRR), which can load a large number of SMRR water-soluble components and better exert antioxidation and antistress effect. Methods: PDA-SMRR nanoparticles (PDA-SMRR) were prepared, and the prescription process was investigated and optimized by single-factor experiments. The particle size, potential, and morphology of the nanoparticles were examined by a laser particle size analyzer and a transmission electron microscope. The drug loading and cumulative release rate were analyzed by dialysis. The cardiomyocytes of neonatal rats were extracted and cultured. The CCK-8 experiment was used to investigate the biological safety of PDA-SMRR and verify the protective effect of PDA-SMRR on oxidative stress-induced cardiomyocytes. Results: The optimal drug loading process was pH value 3.5, drug loading time was 12 h, drug loading temperature was room temperature, and PDA-SMRR was successfully prepared. The morphology and size of the nanoparticles were regular and uniform. The particle size and Zeta potential were (459.2 ± 4.5) nm, (3.01 ± 0.3) mV; In vitro release experiments indicated that SMRR was released slowly by the delivery system. CCK-8 experiments showed that PDA-SMRR had good biological safety and nanoparticles can reduce damaged cardiomyocytes caused by oxidative stress. Conclusion: PDA-SMRR can be used as a multi-component medicine depot for SMRR, with high drug loading and sustained release effect, which can effectively reduce the damage of oxidative damage on myocardial cells.

Comparison and theoretical modeling of capillary electrophoresis analysis for the interaction between caffeine and serum proteins / 药学学报

The method for analyzing the interaction between caffeine and human serum albumin (HSA) was established by capillary electrophoresis. Under physiological conditions, the interaction between ligand (caffeine)-receptor (HSA) was studied with frontier-analysis (FA) method, Hummel-Dreyer (HD) method and plug-plug kinetic (PPK) method. The interaction parameters of caffeine-HSA system were obtained using non-linear equation, Scatchard equation and Klotz equation. The results showed that FA, HD and PPK methods were suitable for caffeine-HSA system, among them, HD method was the best, and the Non-linear equation was the best theoretical model to caffeine-HSA system. Interaction parameter tests showed that caffeine-HSA interaction was a single site interaction and the binding stability was moderate. The mechanism of caffeine-HSA interaction has been elucidated, which can provide valuable information for further research of alkaloids.

Diagnosis and treatment of resistance to the thyroid hormone / 中华实用儿科临床杂志

Resistance to the thyroid hormone is a rare and hereditary thyroid disease,the signs and symptoms are diverse and the onset is hidden.It is often misdiagnosed as a common thyroid disease and given inappropriate diagnosis and treatment.Improper diagnosis and treatment would cause adverse effect on growth and development of sick children.It is necessary to improve awareness,understanding and mastery of this disease,so as to improve the level of clinical diagnosis and treatment.

Value of high-definition magnetic resonance imaging in preoperative evaluation of stage b -Ⅱb cervical cancer / 第二军医大学学报

Objective To explore the application value of high-definition magnetic resonance imaging (MRI) in the assessment of preoperative stage B-ⅡB cervical cancer. Methods A retrospective analysis was conducted on 94 patients with cervical cancer who had received preoperative pelvic examination in Changhai Hospital of Navy Medical University (Second Military Medical University) from Mar. 2015 to Jun. 2017. Fifty-eight of them received conventional MRI examination and 36 received high-definition MRI examination. The accuracy, sensitivity and specificity of the three methods for vaginal and parametrial invasion were evaluated using the postoperative pathological assessments as the gold standard. And the Kappa test was used to perform consistency analysis. Results For vaginal invasion, the accuracy, sensitivity and specificity of pelvic examination were 63.8% (60/94), 53.7% (29/54) and 77.5% (31/40), respectively; those of conventional MRI examination were 58.6% (34/58), 48.5% (16/33) and 72.0% (18/25), respectively; and those of high-definition MRI examination were 83.3% (30/36), 76.5% (13/17) and 89.5% (17/19), respectively. Kappa test showed that the consistency of pathology and pelvic examination and high-definition MRI examination assessments was good in evaluating vaginal invasion (Kappa＝0.297, 0.664; P＝0.002, 0.001). For parametrial invasion, the accuracy, sensitivity and specificity of pelvic examination were 79.8% (75/94), 20.0% (1/5) and 83.1% (74/89), respectively; those of conventional MRI examination were 74.1% (43/58), 31.2% (5/16) and 90.5% (38/42), respectively; and those of high-definition MRI examination were 86.1% (31/36), 60.0% (6/10) and 96.1% (25/26), respectively. Kappa test showed that the consistency of pathology and conventional MRI examination and high-definition MRI examination assessments was good in evaluating parametrial invasion (Kappa＝0.251, 0.618; P＝0.040, 0.001). Conclusion High-definition MRI examination and pathological examination have a good consistency in preoperative assessment of cervical cancer at stage B-ⅡB, and can be a common method for preoperative evaluation of cervical cancer.

Clinical study of preutaneous microwave ablation in the treatment of autonomous functional thyroid nodules / 中华超声影像学杂志

Objective To study the clinical efficacy and safety of microwave ablation (MWA) in the treatment of autonomous functional thyroid nodules(AFTN) . Methods Sixty-seven nodules of 53 AFTN patients who refused or were not suitable for surgical resection and 131I therapy were enrolled in the study . All the nodules were evaluated by ultrasound ,color Doppler flow imaging ( CDFI) and contrast enhanced ultrasound(CEUS) ,and all of them were benign and confirmed by pathology . And then ,percutaneous MWA was performed . Fluid isolation and mobile ablation were used to completely inactivate the nodules ,and CEUS was used to evaluate the efficacy of the treatment . The following items included thyroid hormone level ,nodule volume ,nodular blood supply ,thyroid radionuclide imaging ,conscious symptom ,beauty score and complication . Finally ,the factors influencing the curative effect were analyzed . Results The follow-up period was at least 12 months . Compared with before treatment ,the differences of thyroid hormone level , the volume of nodules ,the nodule blood supply were statistically significant ( P ＜ 0 .01) . The 61 hot nodules" changed to cold or warm nodules" . The differences between the improvement ratio of conscious symptoms and beauty scores were statistically significant( P ＜ 0 .05) . The cure ratio in this study was 81 .13% ,and the incidence of complications was 11 .32% ,and the recurrence ratio was 4 .48% . The nodule volume≥14 .04 ml or in a dangerous position were the main factors affecting the curative effect . Conclusions MWA can inactivate the AFTN in situ ,make it lose the secretory function and reduce the volume of nodules . Therefore ,percutaneous MWA guided by ultrasound and CEUS treatment of AFTN can be regarded as another safe and effective treatment besides surgical resection or 131I therapy .

Optimization of Extraction Technology for Qinhao Nasal Drops by Multi-index Comprehensive Evaluation Method / 中国中医药信息杂志

Objective To optimize extraction process of Qinhao Nasal Drops by multi-index comprehensive evaluation Method. Methods With L9(34) orthogonal design, the content of rupestonic acid, chlorogenic acid, pseudoephedrine hydrochloride, total flavonoids and extract yield were set as indexes, and extraction technology of Qinhao Nasal Drops was optimized.Results Optimum extraction technology was:12 times amount of 60% ethanol, extracted three times. Conclusion The optimized extraction technology is simple, practical, and adapt to the production needs, which can be used as the basis for reasonable development of the preparation.

Assessment of volume status in maintenance hemodialysis patients / 上海交通大学学报（医学版）

Objective · To assess volume status in maintenance hemodialysis (MHD) patients.Methods · Body composition analysis was performed on 128 MHD patients from Renji Hospital,Shanghai Jiao Tong University School of Medicine.The volume status was assessed based on body composition data and predialysis systolic blood pressure (preBPsys),edema grade,brain natriuretic peptide (BNP).Patients were divided into hyperhydrated group (percentage of hydration status,HS％＞ 15％) or normohydrated group (HS％ ≤ 15％).Body composition data were compared,including lean tissue index (LTI) and fat tissue index (FTI).The blood pressure,edema grade,serum calcium,serum phosphate,intact parathyroid hormone (iPTH),hemoglobin,albumin,pre-albumin,hypersensitive C-reactive protein (hs-CRP),serum sodium,and urea clearance Kt/V were compared between two groups.Results · Sixtynine patients were normohydrated and preBPsys reached target;10 patients were overhydrated with higher preBPsys;18 patients had overhydration but preBPsys was in target range.Compared to normohydraed group,patients in hyperhydmted group had more obvious edema,higher BNP level,significantly lower LTI,serum albumin and pre-albumin levels,while serum sodium was significantly higher (P＜0.05).Conclusion· Volume status of hemodialysis patients can be objectively and accurately assessed by body composition analysis using bioimpedance technique with blood pressure,edema grade and biochemical parameters.Hyperhydrated patients may have higher serum sodium level,lower serum albumin,lower hemoglobin,and less lean tissue mass concomitantly.Sodium intake control,nutrition status improvement,and anemia correction may be useful to reduce hyperhydration.

Fructose induces HK-2 ceils to express monocyte chemoattractant protein-1 through uric acid and reactive oxygen species / 上海交通大学学报（医学版）

Objective·To investigate the mechanism of fructose-induced monocyte chemoattratant protein-1(MCP-1) production in HK-2 cells.Methods·The HK-2 cells were divided into fructose incubated (1,5 and 10 mmol/L) group,fructose and ketohexo-kinase inhibitor (KHK-IN) coincubation (fructose 5 mmol/L,KHK-IN was 12,100 and 1 000 nmol/L,respectively) group,uric acid incubation (5,15 and 50 mg/dL) group,fructose and allopurinol co-incubation (fructose 5 mmol/L,allopurinol were 0.01,0.1 and 0.5 mmol/L) group,uric acid and allopurinol co-incubation (uric acid 50 mg/dL,allopttrinol respectively 0.01,0.1and 0.5 mmol/L) group,H2O2 incubation (0.1 and 0.3 mmol/L) group,fructose and N-acetylcysteine (NAC) coincubation (fructose 5 mmol/L,NAC respectively 5,10 and 50 mmol/L) group,and uric acid and NAC co-incubation (uric acid 50 mg/dL,NAC was 5,10and 50 mmol/L,respectively) group.The quantitative PCR method and Western blotting method were used to observe the expression ofMCP-1 mRNA and protein.The effects of fructose and uric acid on the production of ROS in HK-2 cells were observed by using a fluorescent probe.Results·Fructose doseand time-dependently induced MCP-1 gene transcription and protein production in HK-2 cells,which could be blocked by the ketohexo-kinase blockers.Exogenous uric acid induced MCP-1 production in HK-2 cells.Allopurinol inhibited fructose,but not exogenous uric acid-induced MCP-1 expression.Both fructose and uric acid induced ROS generation.Incubation with H2O2promoted MCP-1 production in HK-2 cells.NAC completely inhibited MCP-1production induced by fructose and H2O2.Conclusion·Catalyzed by the ketohexo-kinase,fructose resultes the production of MCP-1 through uric acid and reactive oxygen species.

Pyruvate dehydrogenase activity and pyruvate dehydrogenase kinase 4 expression in skeletal muscle of end-stage renal disease patients / 上海交通大学学报（医学版）

Objective·To explore the changes of pyruvate dehydrogenase (PDH) activity and pyruvate dehydrogenase kinase 4 (PDK4) expression in the end-stage renal disease (ESRD) patients' skeletal muscles. Methods·Skeletal muscle samples were collected from non-chronic kidney disease (non-CKD) patients and ESRD patients. PDH activity was detected by ELISA assay. Real-time qPCR was performed to examine gene transcription levels of PDK1-PDK4 and PDH subunits.Western blotting analysis was used to detect protein expression levels of PDK1 and PDK4. Results·There were no demographic differences between two groups of patients. Plasma creatinine and urea nitrogen were significantly elevated in ESRD group (both P<0.05), while estimated glomerular filtration rate, hemoglobin and plasma albumin in ESRD group were significantly lower than those in non-CKD group (all P<0.05).Skeletal muscle PDH activity in ESRD group was markedly lower than that in non-CKD group(P=0.014).There were no differences in PDK1-PDK4 and PDH subunits mRNA transcription levels between ESRD and non-CKD group.PDK4 protein expression was significantly higher than that in non-CKD group (P=0.000). Conclusion·The decreased PDH activity in ESRD patients' skeletal muscle may be related to up-regulation of PDK4.

Transposition of internal limiting membrane with a non - inverted flap technique for large macular hole / 国际眼科杂志(Guoji Yanke Zazhi)

·AIM:To explore the effectiveness of a new non-inverted pedicle internal limiting membrane ( ILM ) flap transposition technique in the treatment of large macular holes (MH). ·METHODS: This was a prospective pilot study which included 9 patients with 10 eyes in Jiangsu Province People's Hospital from December 2016 to February 2017. All patients was diagnosed with large MH (size >400μ m) by the spectra- domain optical coherence tomography (SD-OCT) and underwent the non-inverted pedicle ILM flap transposition surgery. Best-corrected visual acuity (BCVA), SD-OCT images, and MP-1 microperimetry tests were performed pre-operation, 1d, 1wk, 1, 3, and 6mo post-operation. ·RESULTS:The macular hole closure rate after 6mo was 100%. The averaged BCVA improved from 1. 19 ± 0. 54 (LogMAR) pre-operation to 0.70 ± 0.50 (LogMAR) post-operation (P=0.005). The mean retinal sensitivity within 8° and 2° improved from 3.14±4.52dB to 8.91±5.53dB(P=0.008), and 1.46 ± 2.94dB to 6.33 ± 4.90dB (P=0.008) respectively. Preoperative unstable fixation in seven eyes resolved at the last postoperative follow-up.·CONCLUSION: Our non-inverted pedicle internal ILM flap transposition technique shows effectiveness in the treatment of large macular holes with high MH closure rate and improving visual function.

Analysis of the Carbapenemase Genotype in the Carbapenem-resistant Acinetobacter Baumannii in Traumatology Department / 昆明医科大学学报

Objective To investigate the genotype of D class of carbapenemase of carbapenem－resistant Acinetobacter baumannii in traumatology department, so as to guide the rational use of antibiotics as well as prevent the nosocomial infection. Methods A total of 96 strains of Acinetobacter baumannii were collected in traumatology department. Patient history were analyzed and genotype of carbapenemases of OXA－51,OXA－23,ISAba1－oxa－51 and ISAba1－oxa－23 were analyzed by PCR.Results 70.84% (68/96) of Acinetobacter baumannii were isolated from wound tissue. 12 antibacterial agents were tested, 96 strains of Acinetobacter baumannii showed the highest resistance rate (78.13%) to imipenem and the lowest resistance rate (43.75%) to levofloxacin. Among 23 strains of imipenem－sensitive Acinetobacter baumannii, OXA－ 51 gene expression was not detected in 4 strains, however, OXA－23 gene expression were observed in 5 strains. The gene expression rates of OXA－51,OXA－23, ISAba1－oxa－51 and ISAba1－oxa－23 genes were 100%, 95.89%, 79.45% and 71.23% respectively in 73 strains of imipenem－insensitive Acinetobacter baumannii. The rate of gene expression profile of OXA－51+ISAba1－oxa－51+OXA－23+ISAba1－oxa－23 was 65.75% .Conclusion The strains of imipenem－sensitive Acinetobacter baumannii may have the gene expression of OXA－23 of D class of carbapenemase. The main pattern of carbapenemase－producing was OXA－51+ISAba1－oxa－51+OXA－23+ISAba1－oxa－23 in traumatology department,which might be regarded as one of the mechanisms that led to the high resistance of the bacterium of acinetobacter baumannii to carbapenem antibiotics.

Analysis of 4313 cases of blood culture bacteria / 西安交通大学学报(医学版)

Objective To collect the laboratory parameters and clinical parameters of blood culture positive samples,and analyze the composition and laboratory characteristics of real pathogens by combining with clinical follow-up and anti-infectious treatment outcomes.Methods We conducted a prospective study to isolate the 483 strains of pathogens from 4313 cases of blood samples for clinical examination between March 2013 and March 2015.The results of laboratory and clinical infections were collected for each positive culture and were followed up for clinical follow-up to understand the responsible doctors' experience-based judgment and targeted clinical treatment of antibiotics.After comprehensive analysis we determined the real pathogens and contaminants.Results Of the 483 positive cultures,331 were finally determined as pathogenic ones,accounting for 68.5% of the number of positive isolates; 97 were contaminated bacteria (20.1%); and 55 strains with uncertain pathogenic nature (11.4%).Escherichia coli accounted for the highest proportion (41.2%)of pathogenic bacteria.Coagulase-negative staphylococci took up the highest proportion (75.3%)of the contaminated bacteria.As many as 253 strains (52.4%)were detected from the aerobic or anaerobic bottles.The detection rate of Escherichia coli in anaerobic bottles (23.9%)was higher than that in aerobic bottles (13.8%)(P <0.05).Of 97 strains of positive isolates,only one bottle was reported positive for 90 strains,accounting for (92.8%),and more than two bottles of 7 positive strains,accounting for (7.2%)(P <0.05).34 positive in 24 h (35.1%),77 positive in 48 h (79.4%),the positivebacteria ratio within 48 h (79.4%)was higher than that of bacteria contamination ratio within 24 h (χ2 =38.935, P =0.000),with a significant difference.Conclusion Establishment of contaminated bacteria in blood culture cannot rely solely on laboratory or clinical parameters.It should be combined with the experience of clinicians to determine the clinical response to comprehensive judgments.For the laboratory to determine the presence of contamination,the number of positive bottles and the amount of sun are still two factors of important value.Paying attention to inspection of anaerobic bottles is more conducive to the detection of Escherichia coli.