Evaluation of lateral lymph node metastasis in mid-low rectal cancer and planning of multi-disciplinary treatment / 中华胃肠外科杂志

After the implementation of neoadjuvant chemoradiotherapy and total mesorectal excision, lateral local recurrence becomes the major type of local recurrence after surgery in rectal cancer. Most lateral recurrence develops from enlarged lateral lymph nodes on an initial imaging study. Evidence is accumulating to support the combined use of neoadjuvant chemoradiotherapy and lateral lymph node dissection. The accuracy of diagnosing lateral lymph node metastasis remains poor. The size of lateral lymph nodes is still the most commonly used variable with the most consistent accuracy and the cut-off value ranging from 5 to 8 mm on short axis. The morphological features, differentiation of the primary tumor, circumferential margin, extramural venous invasion, and response to chemoradiotherapy are among other risk factors to predict lateral lymph node metastasis. Planning multiple disciplinary treatment strategies for patients with suspected nodes must consider both the risk of local recurrence and distant metastasis. Total neoadjuvant chemoradiotherapy is the most promising regimen for patients with a high risk of recurrence. Simultaneous Integrated Boost Intensity-Modulated Radiation Therapy seemingly improves the local control of positive lateral nodes. However, its impact on the safety of surgery in patients with no response to the treatment or regrowth of lateral nodes remains unclear. For patients with smaller nodes below the cut-off value or shrunken nodes after treatment, a close follow-up strategy must be performed to detect the recurrence early and perform a salvage surgery. For patients with stratified lateral lymph node metastasis risks, plans containing different multiple disciplinary treatments must be carefully designed for long-term survival and better quality of life.

Progress in intestinal adaptation after enterectomy / 中华胃肠外科杂志

Intestinal adaptation is a spontaneous compensation of the remanent bowel after extensive enterectomy, which improves the absorption capacity of the remanent bowel to energy, fluid and other nutrients. Intestinal adaptation mainly occurs within 2 years after enterectomy, including morphological changes, hyperfunction and hyperphagia. Intestinal adaptation is the key factor for patients with short bowel syndrome to weaning off parenteral nutrition dependence and mainly influenced by length of remanent bowel, type of surgery and colon continuity. In addition, multiple factors including enteral feeding, glucagon-like peptide 2 (GLP-2), growth hormone, gut microbiota and its metabolites regulate intestinal adaptation via multi-biological pathways, such as proliferation and differentiation of stem cell, apoptosis, angiogenesis, nutrients transport related protein expression, gut endocrine etc. Phase III clinical trials have verified the safety and efficacy of teduglutide (long-acting GLP-2) and somatropin (recombinant human growth hormone) in improving intestinal adaptation, and both have been approved for clinical use. We aim to review the current knowledge about characteristics, mechanism, evaluation methods, key factors, clinical strategies of intestinal adaptation.

Effects of Pharmaceutical Management Intervention on Clinical Use of TCM Injection in Primary Medical Insti- tutions / 中国药房

OBJECTIVE：To investigate the effects of pharmaceutical management intervention on the use of TCM injection in primary medical institutions. METHODS ：Twenty grass-roots health centers in Yichun city ，Jiangxi province were randomly selected. Relying on Department of Pharmacy and Health Services of the Municipal Health Committee and the Quality Control Center for Pharmacy Affairs of the City ，Yichun People ’s Hospital took the lead in establishing the prescription evaluation criteria for TCM injection ，training pharmaceutical service skills ，conducting special reviews on prescriptions/medical orders ，improving control measures ，obtaining relevant data of drug use in primary health centers by issuing questionnaires on the use of TCM injection and randomly selecting prescriptions/medical orders for comments. The relevant data without drug administration （before intervention）from Jan. to Jun. 2018 were taken as the non-intervention group ，and the relevant data with drug administration （after intervention）from Jan. to Jun. 2019 were taken as the intervention group. The use of TCM medicine injection ，DDDs，DDC and sequencing ratio were compared before and after intervention. At the same time ，the prescriptions/medical orders of TCM injections before（1 222 copies）and after （1005 copies）intervention were randomly selected for comment and the reasonable situations of the prescriptions/medical orders were compared before and after the intervention. RESULTS ：After intervention ，total amount ， consumption sum and DDDs of top 10 TCM injections in the list of amount were significantly decreased. The reasonable rate of prescriptions and medical orders was 48.04％ before intervention ， but increased to 70.65％ after intervention. Besides ， unreasonable situations before and after intervention all manifested as inappropriate indications. After the intervention ，the unreasonable rates of Xuesaitong powder for injection （lyophilized），Xueshuantong injection ，Xingnaojing injection （two specifications），Shengmai injection ，Xueshuantong for injection （lyophilized）and Qingkailing injection were significantly lower than before intevention （P＜0.05）. CONCLUSIONS ：Pharmaceutical administration intervention can reduce the total amount and the consumption sun of TCM injection in primary medical institutions ，and promote rational drug use in the clinic.

The clinical value of China Savin pollen extract used for skin prick test / 临床耳鼻咽喉头颈外科杂志

The aim of this study is to evaluate the effectiveness and safety of China Savin pollen extract which was used for skin prick test (SPT) in the diagnosis of China Savin pollen allergy. Patients with diagnosis of allergic diseases were collected from Allergy Department of Peking Union Medical College Hospital. All patients were given SPT with China Savin pollen extract, and the mean wheal diameter (MWD) was measured after 15 minutes. Receiver operating characteristic curve (ROC) analysis was performed based on the results of serum specific immunoglobulin E (sIgE). The effectiveness of SPT in the diagnosis of China Savin pollen allergy was evaluated under different diagnostic cutoff values. Adverse events were also recorded to evaluate the safety. A total of 1 029 patients were enrolled in this study without drop out case. There were 1 007 patients in full analysis set (FAS) and 765 patients in per protocol analysis set (PPS). The elimination rate was 25.66%. The area under the ROC curve of FAS is 0.814 (95%: 0.788-0.839); which of PPS is 0.829 (95%: 0.801-0.857). Based on the ROC curve of PPS, the optimal and the 95% specificity diagnostic cutoff values of MWD were 3.25 mm and 4.75 mm respectively. Based on different diagnostic cutoff value (3.00, 3.25 and 4.75 mm), the sensitivities of SPT with China Savin pollen extract were 0.740 0 (95%: 0.701 6-0.778 4), 0.700 (95%: 0.659 8-0.740 2) and 0.532 (95%: 0.488 3-0.575 7) respectively, whereas the specificity was gradually increased in sequence, which was 0.769 8 (95%: 0.719 1-0.820 5), 0.826 4 (95%: 0.780 8-0.872 0) and 0.950 9 (95%: 0.924 9-0.976 9) respectively. There were 7 adverse events observed among 6 patients (rate: 0.583%, 6/1 029). The manifestation was mild. There was no severe adverse event. SPT with China Savin pollen extract is an effective and safe tool for the diagnosis of China Savin pollen allergy. The effectiveness of diagnosis could be improved based on integration of medical history and different diagnostic threshold values of SPT.

Local substrates of non-receptor tyrosine kinases at synaptic sites in neurons / 生理学报

Several non-receptor tyrosine kinase (nRTK) members are expressed in neurons of mammalian brains. Among these neuron-enriched nRTKs, two Src family kinase members (Src and Fyn) are particularly abundant at synaptic sites and have been most extensively studied for their roles in the regulation of synaptic activity and plasticity. Increasing evidence shows that the synaptic subpool of nRTKs interacts with a number of local substrates, including glutamate receptors (both ionotropic and metabotropic glutamate receptors), postsynaptic scaffold proteins, presynaptic proteins, and synapse-enriched enzymes. By phosphorylating specific tyrosine residues in the intracellular domains of these synaptic proteins either constitutively or in an activity-dependent manner, nRTKs regulate these substrates in trafficking, surface expression, and function. Given the high sensitivity of nRTKs to changing synaptic input, nRTKs are considered to act as a critical regulator in the determination of the strength and efficacy of synaptic transmission.

feasibility of direct treatment planning via contrast-enhanced computed tomography: an evaluation of dose differences based on the dimensional dose distribution comparison method

Background: We used a MapCHECK software-based dimensional dose distribution comparison method capable of evaluating point-to-point geometrical dose differences in volume to determine whether doses obtained from an enhanced computed tomography [CT]-based treatment plan, which better defines the target regions and organs at risk, differs from doses obtained from plain CT and then evaluated the feasibility of treatment planning via enhanced CT

Materials and Methods: Forty-three randomly selected patients underwent plain and subsequent enhanced CT with the same settings. Treatment plans developed for the two scans were identical in terms of planning parameters [e.g., isocentre, gantry angle, segments] and monitor units [MU] used for dose calculation. Horizontal and vertical dose distribution planes across the same isocentre were selected from two types of plan; a two-dimensional dose distribution analysis was used to determine the Distance-To-Agree [DTA] pass ratios of corresponding dose distribution planes

Results: Obtained doses at the head and neck [H and N] and pelvic sites did not differ greatly between enhanced and plain CT. However, enhanced CT significantly influenced doses to the lower thoracic oesophagus. A corrected pass ratio that was achieved by non-pass points in lower isodose areas excluded from the statistical analysis had better clinical outcome

Conclusion: Radiation plans with multi-fields and multi-angles can reduce the influence of enhanced CT on torso cases and may even negate its influence on H and N cases. Enhanced CT can be directly used for planning unless the target region contains the lower oesophagus and its surrounding blood vessel whose high density requires correction

Phosphorylation and regulation of glutamate receptors by CaMKII / 生理学报

Ca²⁺/calmodulin-dependent protein kinase II (CaMKII) is the most abundant kinase within excitatory synapses in the mammalian brain. It interacts with and phosphorylates a large number of synaptic proteins, including major ionotropic glutamate receptors (iGluRs) and group I metabotropic glutamate receptors (mGluRs), to constitutively and/or activity-dependently regulate trafficking, subsynaptic localization, and function of the receptors. Among iGluRs, the N-methyl-D-aspartate receptor (NMDAR) is a direct target of CaMKII. By directly binding to an intracellular C-terminal (CT) region of NMDAR GluN2B subunits, CaMKII phosphorylates a serine residue (S1303) in the GluN2B CT. CaMKII also phosphorylates a serine site (S831) in the CT of α-amino-3-hydroxy-5- methylisoxazole-4-propionic acid receptors. This phosphorylation enhances channel conductance and is critical for synaptic plasticity. In addition to iGluRs, CaMKII binds to the proximal CT region of mGluR1a, which enables the kinase to phosphorylate threonine 871. Agonist stimulation of mGluR1a triggers a CaMKII-mediated negative feedback to facilitate endocytosis and desensitization of the receptor. CaMKII also binds to the mGluR5 CT. This binding seems to anchor and accumulate inactive CaMKII at synaptic sites. Active CaMKII dissociates from mGluR5 and may then bind to adjacent GluN2B to mediate the mGluR5-NMDAR coupling. Together, glutamate receptors serve as direct substrates of CaMKII. By phosphorylating these receptors, CaMKII plays a central role in controlling the number and activity of the modified receptors and determining the strength of excitatory synaptic transmission.

Beneficial effect of GABA on experimentaly induced diabetes in CD1 mice

Gama amino butyric acid [GABA] is the major inhibitory neurotransmitter in the mammalian nervous system. Pancreatic beta cells in islets of Langerhans express GABA at the levels comparable to those encountered in the central nervous system. The concentrations of GABA and the number of GABA secreting cells, decrease in diabetic patients and experimental diabetes models. Reports on effects of GABA on insulin secretion have been controversial. In this study we investigated whether or not GABA administration in an animal diabetes model can change insulin and glucagon secretion and improve diabetic symptoms. Seven-week old CD1 mice were used. For inducing diabetes, 40 mg/kg of streptozotocin [STZ] was given intraperitoneally for 5 days. Two months after diabetic induction, animals were divided into two groups, one receiving 200 ?mol of GABA, while the other group received phosphate buffer solution [PBS] for two and half months. After 42 days, the glucose concentration in the GABA treated group decreased significantly compared to the untreated group and the first day. After two and half months, water consumption in the GABA treated group decreased significantly in comparison to the control group. Plasma insulin level increased significantly [0.989 +/- 0.67 vs 0.779 +/- 0.11] while plasma glucagon level decreased significantly [91.71 +/- 4.52 vs 130.07 +/- 18.78]. Glucose tolerance test in the GABA group returned to normal levels. GABA administration by regulation of insulin and glucagon secretion could help treat some diabetic symptoms, and could possibly be used in the future as a therapeutic tool in diabetes

[Effect of GABA on plasma cytokine concentration and beta and alpha cell mass in CD1 diabetic mice]

Type I diabetes is an autoimmune disease associated with T lymphocytes function in beta cells. This process can increase cytokine secretion, which can cause beta cell inflammation and death. Since GABA, [y-aminobutyric acid] is a major inhibitory neurotransmitter, and low concentration of GABA can increase cytokine secretion, the aim of this study was demonstrate to the inhibitory effect of GABA administration on cytokine secretion and decrease in beta cell death and also to show the ability of beta cells in insulin secretion. Seven week old CD1 mice were used. To induce diabetes, animals received 40 mg/kg of STZ five days continuously. Two months later, animals were divided into two groups, one receiving 200 micromole of GABA and the other [controls] the same volume of PBS for 10 weeks. Serum glucagon levels, and alpha cells significantly decreased in the [IL12 IL1beta, TNF alpha] mass and some cytokine levels in the GABA group. Plasma insulin level and beta cell mass significantly increased in comparison to the control group. From the results of this study we conclude that GABA administration causes inhibition in cytokine secretion, improves beta cell mass and increases insulin secretion. May be, in the future, if GABA shows no side effects we can use GABA for type one diabetes

Inhibition of the MAPK/ERK cascade: a potential transcription-dependent mechanism for the amnesic effect of anesthetic propofol / 神经科学通报·英文版

Intravenous anesthetics are known to cause amnesia, but the underlying molecular mechanisms remain elusive. To identify a possible molecular mechanism, we recently turned our attention to a key intracellular signaling pathway organized by a family of mitogen-activated protein kinases (MAPKs). As a prominent synapse-to-nucleus superhighway, MAPKs couple surface glutamate receptors to nuclear transcriptional events essential for the development and/or maintenance of different forms of synaptic plasticity (long-term potentiation and long-term depression) and memory formation. To define the role of MAPK-dependent transcription in the amnesic property of anesthetics, we conducted a series of studies to examine the effect of a prototype intravenous anesthetic propofol on the MAPK response to N-methyl-D-aspartate receptor (NMDAR) stimulation in hippocampal neurons. Our results suggest that propofol possesses the ability to inhibit NMDAR-mediated activation of a classic subclass of MAPKs, extracellular signal-regulated protein kinase 1/2 (ERK1/2). Concurrent inhibition of transcriptional activity also occurs as a result of inhibited responses of ERK1/2 to NMDA. These findings provide first evidence for an inhibitory modulation of the NMDAR-MAPK pathway by an intravenous anesthetic and introduce a new avenue to elucidate a transcription-dependent mechanism processing the amnesic effect of anesthetics.

Adult neural stem/progenitor cells in neurodegenerative repair / 生理学报

Although the mammalian brain has long been thought to be entirely postmitotic, the recent discovery has confirmed an existence of neural stem or progenitor cells in various regions of the adult mammalian brain. Like embryonic stem cells, adult neural progenitor cells possess the capacity of self-renewal and differentiation potential for neurogenesis or gliogenesis. In addition to the subventricular zone and hippocampus where active cell division naturally occurs, adult neural progenitors with neurogenic potential exist in the striatum and the vicinity of dopaminergic neurons in the substantia nigra. Normally, progenitors in those regions proliferate at a low level, and most proliferated cells remain uncommitted. In response to the selective lesion of nigrostriatal dopaminergic pathway by the neurotoxins, such as 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) or 6-hydroxydopamine, progenitors in the injured areas markedly increase their proliferation rate. Depending upon the magnitude and kinetics of the lesion, neurogenesis and gliogenesis were induced in the lesion sites at varying extents. A large number of growth and neurotrophic factors influence proliferation and/or differentiation of progenitor cells under normal and lesioned conditions. Some factors (epidermal and basic fibroblast growth factors and brain-derived neurotrophic factor) are facilitatory, while others (usually bone morphogenetic proteins) are inhibitory, for controlling division and fate of neuronal or glial progenitors. Expression of endogenous factors and their respective receptors in existing and newborn cells are also subject to be altered by the lesion. These genomic responses are considered to be important elements for the formation of a local molecular niche for a given phenotypic cell regeneration. Taken together, adult neural progenitor cells in the nigrostriatal dopaminergic system have the ability to respond to the lesion to repopulate missing cells. The regenerative neuro- or gliogenesis in situ can, at least in part, endogenously compensate injured neural elements, and achieve a self-repair of neurodegenerative disorders such as Parkinson's disease.