Synthesis and biological activity evaluation of phthalimide-donepezil hybrids / 药学学报

A series of phthalimide-donepezil (PTA-DPZ) hybrids (5a-e, 6a-l) were designed, synthesized and evaluated as selective inhibitors of acetylcholinesterase (AChE). The results showed that some hybrids had strong AChE inhibitory activity with half maximal inhibitory concentration (IC50) at nanomolar range, which was better than the control drugs galanthamine and tacrine, and equivalent to DPZ. Compound 6k exhibited the strongest inhibition to AChE with an IC50 value of 0.13 μmol·L-1. Kinetic and molecular modeling studies showed that 6k targeted both catalytic active site and peripheral anionic site of AChE. Moreover, some compounds could inhibit AChE-induced β-amyloid (Aβ) aggregation. In addition, absorption, distribution, metabolism and excretion prediction results showed 6k conforms to the Lipinski's rule of five and had high partition coefficient P value. These compounds, especially 6k, may be considered as a dual-functional lead compound for in-depth research.

Effectiveness of three auxiliary irrigation methods for cleaning the internal walls of root canals of curved isolated teeth / 华西口腔医学杂志

OBJECTIVES@#This study aimed to compare the effectiveness of ultrasound and acoustic and laser cleaning of curved root canals.@*METHODS@#A total of 92 molars with independent root canals with a curvature of 20°-40° were prepared and standardized at 04 25# and stained with gentian violet solution for 72 h. Among them, 52 were randomly divi-ded into four groups for final rinsing (n=13): NI group, PUI group, EDDY group, and PIPS group. Ten samples in each group were cut horizontally along the long axis perpendicular to the root and divided into curved upper, curved, and apical segments. Images were taken with a stereomicroscope and Image J measurements were taken to calculate the depth of rinse penetration. The remaining three samples from each group were split along the long axis of the dentin, photographed by scanning electron microscope to record the dentin tubule exposure and staining layer, and scored for staining layer by double-blind method. SPSS 26.0 software was used to perform statistical analysis and select the best flushing method. An extra 40 samples were randomly divided into four groups for detection of flushing fluid penetration depth (n=10): 10, 20, 30, and 40 s.@*RESULTS@#In the upper part, the mean depth of infiltration was not significantly different between the experimental and control groups (P>0.05). The PIPS group had a significantly lower smear layer score than the control group and the EDDY group (P<0.01). In the curved segment, the mean depth of infiltration was significantly greater in the PUI group than in the control group (P<0.05); the tarnish layer score was lower in each experimental group than in the control group. At the top, the mean depth of infiltration was greater in the PUI and PIPS groups than in the control group (P<0.05), and the smear layer score was lower in the PIPS group than in the other groups (P<0.05). After the time was changed, the depth of infiltration of PUI increased only in the apical segment as the flushing time increased.@*CONCLUSIONS@#The PUI and PIPS methods facilitate the penetration of irrigation solution into the dentin canal in curved root canals, especially in the apical segment. The PIPS technique is effective in removing the smear layer in curved root canals.

Mercury species analysis and tissue distribution in rats after continuous administration of Cinnabaris / 中国中药杂志

Cinnabaris is a traditional Chinese medicine(TCM) commonly used for sedation and tranquilization in clinics, and its safety has always been a concern. This study intends to investigate the species and tissue distribution of mercury in rats after continuous administration of Cinnabaris. In the experiment, 30 rats were randomly divided into the control group(equivalent to 0.5% carboxy-methyl cellulose sodium), low-dose Cinnabaris group(0.2 g·kg~(-1)), high-dose Cinnabaris group(2 g·kg~(-1)), pseudogerm-free control group(equivalent to 0.5% sodium carboxymethyl cellulose), and pseudogerm-free Cinnabaris group(2 g·kg~(-1)). They were orally administered for 30 consecutive days. Ultrasound-assisted acid extraction method combined with high performance liquid chromatography and inductively coupled plasma-mass spectrometry(HPLC-ICP-MS) was adopted to determine inorganic mercury [Hg(Ⅱ)], methylmercury(MeHg), and ethylmercury(EtHg) in different tissue, plasma, urine, and feces of rats. The optimal detection conditions and extraction methods were optimized, and the linearity(R~2>0.999 3), precision(RSD<7.0%), and accuracy(spike recoveries ranged from 73.05% to 109.5%) of all the mercury species were satisfied, meeting the requirements of analysis. The results of mercury species detection showed that Hg(Ⅱ) was detected in all the tissue of the five experimental groups, and the main accumulating organs were the intestinal tract, stomach, and kidney. MeHg existed at a low concentration in most tissue, and EtHg was not detected in all groups. In addition, pathological examination results showed that hepatocyte vacuolar degeneration, loose cytoplasm, light staining, and mononuclear cell infiltration were observed in the high-dose Cinnabaris group, low-dose Cinnabaris group, and pseudogerm-free Cinnabaris group, with slightly milder lesions in the low-dose Cinnabaris group. Hydrous degeneration of renal tubular epithelium could be seen in the high-dose Cinnabaris group and pseudogerm-free Cinnabaris group, but there was no significant difference between the other groups and the control group. No abnormal changes were found in the brain tissue of rats in each group. This paper studied the different mercury species and tissue distribution in normal and pseudogerm-free rats after continuous administration of Cinnabaris for 30 days and clarified its effects on the tissue structure of the liver, kidney, and brain, which provided supporting evidence for the safety evaluation of Cinnabaris.

Comparison of follow-up treatment regimens for colorectal cancer liver metastases without objective response to neoadjuvant chemotherapy: direct surgery or surgery after second-line chemotherapy / 中华外科杂志

Objective: To compare the effect of direct surgery or surgery after second-line chemotherapy for colorectal cancer patients with liver metastases who did not achieve objective remission after neoadjuvant chemotherapy. Methods: A retrospective case cohort study was used. The clinical and pathological data of 107 patients with colorectal cancer liver metastases who did not achieve objective response to neoadjuvant chemotherapy at Department of Hepatobiliary Surgery,Cancer Hospital,Chinese Academy of Medical Sciences from December 2008 to December 2016 were retrospectively collected. There were 71 males and 36 females, median age was 57 years (range: 28 to 79 years). According to the different treatment regimens after neoadjuvant chemotherapy,107 cases were divided into a direct surgery group (direct group,n=65) and an operation after receiving second-line chemotherapy group (second-line group,n=42). The propensity score matching(PSM) of the Logistic regression model was used to match the bilobar distribution of liver metastases and the number of first-line chemotherapy cycles in the two groups of patients. The caliper value was set to 0.10 and the matching ratio was 1∶2. T test, Mann-Whitney U test, χ2 test or Fisher's exat test was used to analyzed the data between the tuo groups, respectively. Survival analysis design was used to investigate the difference in prognosis between the two groups of patients. Results: The follow-up time(M(IQR)) was 56.3(34.3) months (range: 2.1 to 95.0 months),and all patients were followed up. After PSM,there were 28 cases in the direct group and 42 cases in the second-line group, there were no significant differences in whether R0 resection was feasible,blood loss,blood transfusion,postoperative complications and postoperative hospital stay between the two groups (all P>0.05). The 1,3,and 5-year progression-free survival(PFS) rates of the direct group were 40.0%,16.5%,and 11.0%,and the 1,3,and 5-year overall survival(OS) rates were 98.5%,61.2%,and 41.4%,respectively, the second-line group 1,3,5 years PFS rates were 35.7%,14.3%,14.3%,1,3,5-year OS rate were 95.2%,55.1%,44.4%,respectively. The median PFS time of the direct group and the second-line group was 8.5 months and 7.5 months,respectively,and the difference was not statistically significant (P=0.826). The median OS time of the direct group and the second-line group were 33.8 months and 46.9 months,respectively. The difference was not statistically significant(P=0.646).The median PFS time of the direct group and second-line chemotherapy complete remission and partial remission group(CR/PR group) was 10.2 months and 9.1 months,respectively,and the difference was not statistically significant(P=0.669). The median OS time of the direct group and the second-line CR/PR group was 51.0 months and 46.9 months,respectively,and the difference was not statistically significant(P=0.427). The results of survival analysis suggested that major liver resection was an independent prognosis factor for PFS (HR=1.809,95%CI: 1.067 to 3.067,P=0.028) and OS(HR=2.751,95%CI: 1.317 to 5.747,P=0.007). Second-line chemotherapy was not an independent prognostic factor for PFS (HR=0.945, 95%CI:0.570 to 1.567,P=0.828) and OS (HR=0.866,95%CI: 0.468 to 1.602,P=0.646). Conclusions: There is no significant difference in the short-term outcome and long-term prognosis between direct surgery patients and second-line chemotherapy followed by surgery. Second-line chemotherapy is not an independent prognostic factor for colorectal cancer liver metastases patients who fail to achieve objective response after neoadjuvant chemotherapy.

Clinical characteristics of Chlamydia psittaci pneumonia: an analysis of 13 cases / 中华全科医师杂志

Objective:To analyze the clinical characteristics of pneumonia caused by Chlamydia psittaci (C. psitttaci). Methods:A retrospective analysis was performed on the clinical data of 13 consecutive patients with C. psitttaci pneumonia admitted to the First Affiliated Hospital of Xiamen University from November 2018 to February 2021. Results:All 13 cases had symptoms of fatigue and 6 cases had headache. At consultation, the ΔSequential Organ Failure Assessment (SOFA) scores of all patients were ≥2 points. According to the Pneumonia Severity Index (PSI) score, 2 patients were grade Ⅱ and the other 11 patients were grade Ⅳ or Ⅴ. Laboratory tests showed that C-reactive protein (CRP) and procalcitonin (PCT) levels were elevated in all patients; CRP≥100 mg/L was found in 11 cases and PCT≥0.5 ng/ml was found in 9 cases.There were 12 cases with respiratory failure and 12 cases with elevated transaminase. Chest CT scans showed multiple patchy exudative shadow, focal consolidation and air bronchial sign; and the lesions were mainly in the lower lungs (8 cases). C. psitttaci infections were confirmed by metagenomics next-generation sequencing (mNGS) and the patients′ conditions improved rapidly after timely adjustment of doxycycline based drug treatment and active organ support. The lesions were completely absorbed without residual fibrous cord changes and the prognosis was good. Conclusions:Pneumonia caused by C. psitttaci usually presents sepsis, and the disease progresses rapidly. The mNGS is of value for the early diagnosis of C. psitttaci pneumonia. Timely adjustment of antibiotics treatment after etiological diagnosis can lead to a good prognosis.

Synthesis, cholinesterase inhibition and hepatotoxicity of tacrine-phenol-bifendate hybrids / 药学学报

A series of tacrine-phenol-bifendate hybrids (7a-7e, 8a-8e) were designed, synthesized and evaluated as inhibitors of cholinesterases (ChEs) with low hepatotoxicity. All the compounds had potent ChEs inhibitory activity with half-inhibitory concentration (IC50) values at the nanomolar range. Compound 8d exhibited the strongest inhibition to acetylcholinesterase (AChE) with an IC50 value of 156.39 nmol·L-1 and compound 7b showed the most potent inhibition for butyrylcholinesterase with IC50 value of 16.33 nmol·L-1. Kinetic and molecular modeling studies showed that 8d targeted both the catalytic active site and the peripheral anionic site of AChE. In addition, these compounds showed low toxicity to hepatocytes, and compound 8d did not increase the level of reactive oxygen species in HepG2 cells.

Total Glucosides of Paeony Improve Renal Injury in Mice with Systemic Lupus Erythematosus by Regulating TLR9/MyD88/NF-κB Pathway / 中国实验方剂学杂志

ObjectiveTo investigate the intervention effect of total glucosides of paeony （TGP） on the renal injury of MRL/lpr mice based on the Toll-like receptor 9 （TLR9）/myeloid differentiation factor 88 （MyD88）/nuclear transcription factor-κB （NF-κB） signaling pathway and explore the immunological mechanism of TGP in preventing and treating systemic lupus erythematosus （SLE）. MethodMRL/lpr female mice of SPF grade were randomly divided into a model group， a dexamethasone group （0.15 g·kg-1）， and high- （0.078 g·kg-1） and low-dose （0.039 g·kg-1） TGP groups， and female C57BL/6J mice were assigned to a blank group， with 7 mice in each group. Mice in each group were treated with corresponding drugs or normal saline by gavage at the same time every day. After 4 weeks， samples were collected. The kidney and spleen were weighed， and the organ index was calculated. Serum creatinine （SCr） and blood urea nitrogen （BUN） levels in each group were detected by biochemical assay. Hematoxylin-eosin （HE） staining was used to observe the histopathological changes in the kidney. The degree of renal fibrosis was evaluated by Masson staining. The serum levels of interleukin （IL）-2， interferon （IFN）-α， IL-4， and anti-nuclear antibody （ANA） were detected by enzyme-linked immunosorbent assay （ELISA）. The mRNA expression of TLR9， MyD88， and NF-κB p65 in renal tissues was detected by real-time quantitative polymerase chain reaction （Real-time PCR）. The protein expression of TLR9 and NF-κB p65 in renal tissues was detected by immunofluorescence. The protein expression of TLR9， MyD88， and NF-κB p65 in renal and spleen tissues was tested by Western blot. ResultCompared with the blank group， the model group showed increased SCr， BUN， spleen index， and kidney index （P<0.05）， deteriorated pathological injury and fibrosis in renal tissues， elevated serum levels of IFN-α， IL-4， and ANA， decreased level of IL-2 （P<0.05）， and up-regulated TLR9， MyD88， and NF-κB p65 mRNA and protein levels in the kidney and spleen （P<0.05）. Compared with the model group， the TGP groups displayed reduced SCr， BUN， spleen index， and kidney index （P<0.05）， relieved pathological damage and fibrosis in renal tissues， decreased serum levels of IFN-α， IL-4， and ANA （P<0.05）， increased level of IL-2， and declining mRNA and protein expression levels of TLR9， MyD88， and NF-κB p65 in the kidney and spleen （P<0.05）. ConclusionTGP may inhibit the expression of downstream inflammatory factors to regulate immunity and resist SLE-induced renal injury by regulating the TLR9/MyD88/NF-κB signaling pathway.

The role of contrast-enhanced ultrasound imaging in preoperative screening of patients with uterine fibroids treated by magnetic resonance guided focused ultrasound / 中华超声影像学杂志

Objective:To investigate the role of contrast-enhanced ultrasound (CEUS) features in preoperative screening of patients with uterine fibroids treated by magnetic resonance imaging guided focused ultrasound (MRgFUS).Methods:The preoperative CEUS features of 28 patients (32 lesions) with uterine fibroids treated by MRgFUS in Xijing Hospital of Air Force Military Medical University from January 2018 to March 2021 were analyzed. The relationships between the imaging features of lesions and the necrosis range were evaluated, which included echo intensity in gray-scale ultrasound, the patterns of the perfusion intensity, perfusion distribution, the contrast agent into the model, lesions with entangled branch vessels, ring-like enhancement, and perfusion regression.Results:The gray-scale ultrasound showed that 68.75%(22/32) lesions were hypoechoic. The CEUS showed that 81.25%(26/32) lesions were iso/hypo-enhancement, 65.63%(21/32) lesions were heterogeneous enhancement, 68.75%(22/32) lesions with entangled branch vessels, 71.88%(23/32) lesions with ring-like enhancement, and 75%(24/32) lesions with fast-out enhancement. The 6 indicators above-mentioned had effects on the non-perfusion volume ratio≥50%, the differences were statistically significant (all P<0.05). Conclusions:CEUS can evaluate the blood flow characteristics in uterine fibroids, providing important information for preoperative screening of uterine fibroids for MRgFUS ablation.

Effect and Safety of Modified Buzhong Yiqitang on VEGF， IGF-1， TGF-β1， and Immune Function in Postoperative Patients with Non-small Cell Lung Cancer After Chemotherapy / 中国实验方剂学杂志

Objective:To explore the application value of modified Buzhong Yiqitang （BZYQT） in the treatment of postoperative patients with non-small cell lung cancer （Qi deficiency in lung and spleen） after chemotherapy， and to observe its effect on tumor angiogenesis， immune function， tumor indicators， and lung function indicators. Method:Ninety-six patients who were treated in the Kunming municipal hospital of traditional Chinese medicine from March 2018 to February 2020 due to postoperative chemotherapy for non-small cell lung cancer were selected and assigned into a control group （<italic>n</italic>=48， western medicine） and an observation group （<italic>n</italic>=48， western medicine+modified BZYQT） by the random number table. The curative efficacies were compared after the treatment. Result:After treatment， the serum levels of carcinoembryonic antigen （CEA）， cytokeratin 19 fragment 21-1 （CYFRA21-1）， serum insulin-like growth factor-1 （IGF-1）， vascular endothelial growth factor （VEGF）， and transforming growth factor（TGF）-<italic>β</italic>₁ in the observation group were lower than those in the control group （<italic>P</italic><0.05）， while the serum CD4⁺/CD8⁺，CD4⁺ cells， immunoglobulin G （IgG） levels， forced expiratory volume in one second （FEV₁），and FEV₁/forced vital capacity （FVC） in the observation group were higher than those in the control group （<italic>P</italic><0.05）. A significant difference was observed in the total response rate between the observation group ［56.25% （27/48）］ and the control group ［35.42% （17/48）］ （<italic>χ</italic>²＝4.191，<italic>P</italic><0.05）. For adverse reactions，the incidence of bone marrow suppression（<italic>χ</italic>²＝4.002）， gastrointestinal reaction （<italic>χ</italic>²＝7.069），and hepatic and renal injury （<italic>χ</italic>²＝5.151） was lower in the observation group than in the control group （<italic>P</italic><0.05）. Conclusion:For postoperative patients with non-small cell lung cancer （Qi deficiency in lung and spleen） after chemotherapy， western medicine combined with modified BZYQT could ameliorate immune function， promote pulmonary function recovery， improve clinical efficacy， and reduce the incidence of adverse reactions.

Metabolic engineering of L-cysteine supply modules for enhanced production of bacitracin in Bacillus licheniformis / 生物工程学报

Bacitracin is a broad-spectrum antibiotics mainly produced by Bacillus, and is used as veterinary medicine in the fields of livestock and poultry breeding. Insufficient supply of precursor amino acids might be an important factor that hinders high-level microbial production of bacitracin. We investigated the effect of strengthening L-cysteine supply on bacitracin production by an industrial bacitracin producer, Bacillus licheniformis DW2. Overexpression of cysK encoding L-cysteine synthase led to a 9.17% increase of the bacitracin titer. Moreover, overexpression of cysE encoding L-serine acetyltransferase and cysP encoding thiosulfate/sulfate intracellular transporter increased the bacitracin titers by 7.23% and 8.52%, respectively. Moreover, overexpression of a putative cystine importer TcyP led to a 29.19% increase of intracellular L-cysteine, and bacitracin titer was increased by 7.79%. Subsequently, the strong promoter PbacA was used to replace the promoters of genes cysP, cysE and tcyP in strain DW2::ysK, respectively. The resulted strain CYS4 (DW2::cysK-PbacA-(cysP)-PbacA(cysE)- PbacA(tcyP) produced 910.02 U/mL bacitracin, which was 21.10% higher than that of the original strain DW2 (747.71 U/mL). Together with the experiments in 3 L fermenters, this research demonstrated that enhancing intracellular L-cysteine supply is an effective strategy to increase bacitracin production of B. licheniformis.

Individual mortality risk predictive system of patients with acute-on-chronic liver failure based on a random survival forest model / 中华医学杂志(英文版)

BACKGROUND@#The basis of individualized treatment should be individualized mortality risk predictive information. The present study aimed to develop an online individual mortality risk predictive tool for acute-on-chronic liver failure (ACLF) patients based on a random survival forest (RSF) algorithm.@*METHODS@#The current study retrospectively enrolled ACLF patients from the Department of Infectious Diseases of The First People's Hospital of Foshan, Shunde Hospital of Southern Medical University, and Jiangmen Central Hospital. Two hundred seventy-six consecutive ACLF patients were included in the present study as a model cohort (n = 276). Then the current study constructed a validation cohort by drawing patients from the model dataset based on the resampling method (n = 276). The RSF algorithm was used to develop an individual prognostic model for ACLF patients. The Brier score was used to evaluate the diagnostic accuracy of prognostic models. The weighted mean rank estimation method was used to compare the differences between the areas under the time-dependent ROC curves (AUROCs) of prognostic models.@*RESULTS@#Multivariate Cox regression identified hepatic encephalopathy (HE), age, serum sodium level, acute kidney injury (AKI), red cell distribution width (RDW), and international normalization index (INR) as independent risk factors for ACLF patients. A simplified RSF model was developed based on these previous risk factors. The AUROCs for predicting 3-, 6-, and 12-month mortality were 0.916, 0.916, and 0.905 for the RSF model and 0.872, 0.866, and 0.848 for the Cox model in the model cohort, respectively. The Brier scores were 0.119, 0.119, and 0.128 for the RSF model and 0.138, 0.146, and 0.156 for the Cox model, respectively. The nonparametric comparison suggested that the RSF model was superior to the Cox model for predicting the prognosis of ACLF patients.@*CONCLUSIONS@#The current study developed a novel online individual mortality risk predictive tool that could predict individual mortality risk predictive curves for individual patients. Additionally, the current online individual mortality risk predictive tool could further provide predicted mortality percentages and 95% confidence intervals at user-defined time points.

Research progress on naturally-occurring and semi-synthetic ocotillol-type ginsenosides in the genus Panax L. (Araliaceae) / 中国天然药物

Ocotillol (OT)-type ginsenosides, one subtype of ginsenosides, consist of a dammarane skeleton and a tetrahydrofuran ring. Most naturally-occurring OT-type ginsenosides exist in Panax species, particularly in Panax quinquefolius, which may be attributed to the warm and humid climate of its native areas. Till now, merely 28 types of naturally-occurring OT-type ginsenosides have been isolated. In contrast, semi-synthesized OT-type ginsenosides are attracted considerable attentions. These ginsenosides can be obtained through oxidation and cyclization of side chains of dammarane-type ginsenosides, and other methods, which may change their physical and chemical properties and further improve their bioavailabilities. It is also notable that the pharmacological activities of ginsenosides are closely related to the stereoisomers caused by the configuration at C-20. Semi-synthesis of OT-type ginsenosides can facilitate our understanding of the biosynthesis, transformation and metabolism of OT-type ginsenosides in the body. This review will systematically summarize the research progress on naturally-occurring and semi-synthetic OT-type ginsenosides, which provides a theoretical basis for their bioactivity-guided research.

Propeptide-mediated protein folding: mechanism and its impact on lipase / 生物工程学报

The formation of most proteins consists of two steps: the synthesis of precursor proteins and the synthesis of functional proteins. In these processes, propeptides play important roles in assisting protein folding or inhibiting its activity. As an important polypeptide chain coded by a gene sequence in lipase gene, propeptide usually functions as an intramolecular chaperone, assisting enzyme molecule folding. Meanwhile, some specific sites on propeptide such as glycosylated sites, have important effect on the activity, stability in extreme environment, methanol resistance and the substrate specificity of the lipase. Studying the mechanism of propeptide-mediated protein folding, as well as the influence of propeptide on lipases, will allow to regulate lipase by alternating the propeptide folding behavior and in turn pave new ways for protein engineering research.

Advances in local ablation therapy for liver cancer with portal hypertension / 临床肝胆病杂志

With the comprehensive application of a variety of treatment methods, the survival time of patients with primary liver cancer is gradually increasing. For patients with early-stage liver cancer and portal hypertension, local ablation therapy can achieve long-term survival and play a positive role in stabilizing portal venous pressure, preserving liver function, and reducing complications. In addition, it can be combined with other techniques such as transarterial chemoembolization, transjugular intrahepatic portosystemic shunt, splenectomy, and pericardial devascularization to further improve treatment outcome. Several measures can be taken in the perioperative period to improve the management efficiency of patients after ablation, such as objective evaluation of portal venous pressure, prevention of esophagogastric variceal bleeding, correction of hypersplenism, prevention of postoperative liver failure, and multidisciplinary team management.

Relationship between Postmortem Interval and FTIR Spectroscopy Changes of the Rat Skin / 法医学杂志

Objective To infer postmortem interval （PMI） based on spectral changes of the dorsal skin of rats within 15 days postmortem using Fourier transform infrared （FTIR） spectroscopy. Methods The rats were sacrificed by cervical dislocation after anesthesia, and then placed at 25 ℃ and relative humidity of 50%. The FTIR spectral data collected from the dorsal skin at PMI points were modeled with machine learning technique. Results There was no significant difference of absorption peak location among all the PMI groups but their peak intensities changed as a function of PMIs. The model for PMI estimation was constructed using partial least squares （PLS） regression, reaching a R2 of 0.92 and a root mean square error （RMSE） of 1.30 d. As shown in variable importance for projection （VIP）, four spectral bands including 1 760-1 700 cm-1, 1 660-1 640 cm-1, 1 580-1 540 cm-1 and 1 460-1 420 cm-1 were determined as important contributions to model prediction. Conclusion Application of the FTIR technique to detect postmortem spectral changes of the rat skin provides a novel proposal for PMI estimation.

Determination of Electrocution Using Fourier Transform Infrared Microspectroscopy and Machine Learning Algorithm / 法医学杂志

Objective To analyze the differences among electrical damage, burns and abrasions in pig skin using Fourier transform infrared microspectroscopy （FTIR-MSP） combined with machine learning algorithm, to construct three kinds of skin injury determination models and select characteristic markers of electric injuries, in order to provide a new method for skin electric mark identification. Methods Models of electrical damage, burns and abrasions in pig skin were established. Morphological changes of different injuries were examined using traditional HE staining. The FTIR-MSP was used to detect the epidermal cell spectrum. Principal component method and partial least squares method were used to analyze the injury classification. Linear discriminant and support vector machine were used to construct the classification model, and factor loading was used to select the characteristic markers. Results Compared with the control group, the epidermal cells of the electrical damage group, burn group and abrasion group showed polarization, which was more obvious in the electrical damage group and burn group. Different types of damage was distinguished by principal component and partial least squares method. Linear discriminant and support vector machine models could effectively diagnose different damages. The absorption peaks at 2 923 cm-1, 2 854 cm-1, 1 623 cm-1, and 1 535 cm-1 showed significant differences in different injury groups. The peak intensity of electrical injury's 2 923 cm-1 absorption peak was the highest. Conclusion FTIR-MSP combined with machine learning algorithm provides a new technique to diagnose skin electrical damage and identification electrocution.

Application of a modified paramedian lower lip-submandibular approach in maxillary (subtotal) total resection / 华西口腔医学杂志

OBJECTIVE@#To investigate the clinical efficacy of a modified paramedian lower lip-submandibular approach for maxillary (subtotal) total resection.@*METHODS@#Eleven patients of maxillary tumors underwent maxillary (subtotal) total resection through the modified paramedian lower lip-submandibular approach. Clinical follow-up visits were conducted to evaluate appearance restoration, facial nerve functional status, parotid gland functional status, and orbital region complication.@*RESULTS@#During the follow-up period of 6-36 months, the appearance of all 11 patients recovered well. All cases presented hidden scars. No facial nerve and parotid duct injury, lower eyelid edema, lower eyelid ectropion, or epiphora in all cases was observed.@*CONCLUSIONS@#Applying modified paramedian lower lip-submandibular approach to maxillary (subtotal) total resection effectively reduces incidence of orbital region complications including lower eyelid edema, lower eyelid ectropion, and epiphora, which often occur to traditional approach. The modified approach produces more subtle scars than other methods and should be applied to treatment of maxillary (subtotal) total resection.

Value of conventional ultrasound combined with contrast-enhanced ultrasound in differential diagnosis of thyroid TI-RADS 3-5 nodules / 中华超声影像学杂志

Objective To evaluate the diagnostic value of gray-scale ultrasound combined with contrast-enhanced ultrasound (CEUS) in thyroid imaging and reporting system ( TI-RADS) 3-5 nodules of American College of Radiology ( ACR) . Methods The 208 patients( 216 nodules) who underwent thyroid contrast-enhanced ultrasound examination from April 2014 to December 2016 were retrospectively analyzed . The ACR TI-RADS classification and contrast-enhanced mode of thyroid ultrasound were evaluated . The benign and malignant thyroid lesions were constructed through the analysis of contrast-enhanced mode of thyroid benign and malignant lesions in the past literature and the preliminary study of our group . Prediction model of gray scale combined with contrast-enhanced ultrasound for lesions were established . Besides ,the sensitivity ,specificity and accuracy of gray scale ultrasound combined with contrast-enhanced ultrasound prediction model for differential diagnosis of benign and malignant thyroid lesions were calculated based on the results of puncture biopsy or surgical pathology as the gold standard . Results Compared with pathological results , the positive predictive value , negative predictive value , accuracy , sensitivity and specificity of gray scale combined with contrast-enhanced ultrasound in evaluating thyroid nodules were 90 .8％ ,93 .3％ ,91 .2％ ,98 .8％ and 62 .2％ ,respectively . Conclusions Gray-scale ultrasound combined with contrast-enhanced ultrasound can provide clinical value in differential diagnosis of benign and malignant TI-RADS 3-5 thyroid nodules .

Serum metabolomics of small cell lung cancer patients based on UPLC-TOF/MS / 实用肿瘤学杂志

Objective The objective of this study was to explore the differences of serum metabolomics between small cell lung cancer(SCLC)patients and healthy volunteers,and to discover serum potential biomarkers for identification and small cell lung cancer staging. Methods Ultra-performance liquid chromatography time of flight mass spectrometry(UPLS-TOF/MS)was used to establish the serum metabolic profile of SCLC. Principal Component Analysis(PCA)and orthogonal hidden variables were analyzed by the EZinfo2. 0 software. Orthogonal Partial Least Squares Discriminant Analysis(OPLS-DA)was used to analyze the metabolic differ-ences between the case and normal control groups. Through cluster analysis using HMDB and METLIN database to search for the exact mass-to-charge ratio of the difference,preliminary identification of some substances with significant differences was carried out. Results Ten differential metabolites such as lysophosphatidylcholine between patients and control groups were screened and identi-fied by mass spectrometry and database search. There were 10 different metabolites such as glycocholic acid in the contour analysis of SCLC patients with different stages. Conclusion There is a significant difference in serum metabolism between SCLC patients and healthy controls. The discovery of differential metabolites provides experimental evidence for the identification of small cell lung cancer and potential markers of staging.

Effect of emodin on gut microbiota of rats with acute kidney failure / 中国中药杂志

The aim of this paper was to investigate the effect of emodin on gut microbiota in acute kidney injury rats( AKI). Rats were randomly divided into several groups: normal group,model group,low-dose of emodin group( 10 mg·kg~(-1)),medium-dose of emodin group( 25 mg·kg~(-1)),high-dose of emodin group( 50 mg·kg~(-1)) and control group( 5 mg·kg~(-1) of benazepril hydrochloride).The AKI model rats were established by intraperitoneal injection of small dose of gentamicin sulfate for 7 days. Two hours after intraperitoneal injection,except for the normal group and the model group,the other groups were given corresponding doses of drugs for 15 days. The serum levels of serum creatinine( SCr),urea nitrogen( BUN),plasma endotoxin level,24 h urinary protein and D-lactate in the plasma were determined by sarcosine oxidase,urease method,tal reagent method,bromo cresol chloroform method and double antibody sandwich enzyme-linked immunoadsorbent assay,respectively. Gut microbial communities were assayed by fluorescent quantitative PCR methods. HE staining was used to detect the pathological changes of the kidneys. Compared with the normal group,there were significant differences in body weight,urinary protein( UTP),bacterial endotoxin,urea nitrogen,creatinine,D-lactate in the plasma and four bacterial contents in the model group( P<0. 05). The urinary protein,urea nitrogen,D-lactate,creatinine and plasma bacterial endotoxin in control group and each emodin group were lower than those in model group,especially for high-dose of emodin( P<0. 01). Moreover,pathology resolution in high-dose emodin was better than other groups. Except for low-dose of emodin group,qRT-PCR data suggested that the amounts of Escherichia coli and Enterococcus in medication administration group were increased,while the amounts of Lactobacilli and Bifidobacterium were reduced compared with model group( P<0. 05),especially for high-dose of emodin( P<0. 01). There is a clear imbalance of gut microbiota in rats with AKI. Emodin could regulate the imbalance of gut microbiota,which might be one of the mechanisms of its effects on AKI rats.