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Nitrite poses a serious threat to intensive aquaculture. Protein, as a major nutrient in animals, is vital for protecting animal tissues from damage. In this study, we investigated the protective effect of dietary protein on gill tissue structure and the underlying mechanisms in sub-adult grass carp (Ctenopharyngodon idella) exposed to nitrite stress. Six iso-energetic semi-purified diets containing different protein levels (16–31 %) were formulated, and fed to fish for 60 d. The fish were then exposed to a nitrite solution for 4 d. Histopathological observation and determination of related indices (serum glucose, serum cortisol, nitric oxide, peroxynitrite, reactive oxygen species, malondialdehyde, and protein carbonyl) showed that 22–25 % dietary protein significantly alleviated the nitrite-induced stress response, gill tissue damage and oxidative damage. Further research found that a suitable dietary protein suppressed the nitrite-induced endoplasmic reticulum stress (ERS) 78 kDa glucose-regulated protein (GRP78) related signaling pathway which possibly activated autophagy and apoptosis. Interestingly, we discovered that proper dietary protein reduced autophagy, probably through unc-51-like kinase 1 (Ulk1), BCL-2-interacting myosin-like coiled-coil protein (Beclin1), autophagy-related gene 5 (Atg5), Atg12, microtubule-associated protein1 light chain 3 (LC3), BCL-2 interacting protein 3 (BNIP3) and autophagy receptor P62 (p62). We also found that an appropriate dietary protein inhibited nitrite-induced apoptosis via mitochondrial and death receptor pathways. In summary, our findings are the first to demonstrate that 22–25 % of dietary protein levels can play a protective role against nitrite-induced gill injury. [Display omitted] • Optimal dietary protein significantly alleviated nitrite-induced stress response. • Optimal dietary protein reduced nitrite-induced tissue damage and oxidative damage. • Appropriate dietary protein suppressed nitrite-induced ER stress of fish. • Suitable dietary protein inhibited nitrite-induced autophagy and apoptosis of fish. [ABSTRACT FROM AUTHOR]

Background: CD8+ T cells (Cytotoxic T cells, Tc) are known to play a critical role in the pathogenesis of smoking related airway inflammation including chronic obstructive pulmonary disease (COPD). However, how cigarette smoke directly impacts systematic CD8+ T cell and regulatory T cell (Treg) subsets, especially by modulating muscarinic acetylcholine receptors (MRs), has yet to be well elucidated. Methods: Circulating CD8+ Tc/Tregs in healthy nonsmokers (n = 15), healthy smokers (n = 15) and COPD patients (n = 18) were evaluated by flow cytometry after incubating with anti-CD3, anti-CD8, anti-CD25, anti-Foxp3 antibodies. Peripheral blood T cells (PBT cells) from healthy nonsmokers were cultured in the presence of cigarette smoke extract (CSE) alone or combined with MRs agonist/antagonist for 5 days. Proliferation and apoptosis were evaluated by flow cytometry using Ki-67/Annexin-V antibodies to measure the effects of CSE on the survival of CD8+ Tc/Tregs. Results: While COPD patients have elevated circulating percentage of CD8+ T cells, healthy smokers have higher frequency of CD8+ Tregs. Elevated percentages of CD8+ T cells correlated inversely with declined FEV1 in COPD. CSE promoted the proliferation and inhibited the apoptosis of CD8+ T cells, while facilitated both the proliferation and apoptosis of CD8+ Tregs. Notably, the effects of CSE on CD8+ Tc/Tregs can be mostly simulated or attenuated by muscarine and atropine, the MR agonist and antagonist, respectively. However, neither muscarine nor atropine influenced the apoptosis of CD8+ Tregs. Conclusion: The results imply that cigarette smoking likely facilitates a proinflammatory state in smokers, which is partially mediated by MR dysfunction. The MR antagonist may be a beneficial drug candidate for cigarette smoke-induced chronic airway inflammation. [ABSTRACT FROM AUTHOR]

Based on the early-established spatial model for 3D representation of acupoints, a comprehensive visible human model was developed, incorporated with a linked symbolic description regarding anatomical terms and their relations, especially for description of the Traditional Chinese Medicine (TCM) knowledge. The model of the intelligent object, the organization of the semantic network, the display mode of TCM concepts and the extension of TCM contents were discussed. The relationships of dangerous acupoints and their anatomical structures were also originally explored. The TCM knowledge base system based on the network of "intelligent object" was addressed. A 3D anatomical atlas of acupuncture is being prepared. [ABSTRACT FROM AUTHOR]

Objective To investigate clinicians' practice and opinions on sedation therapy in end-stage patients at Peking Union Medical College Hospital. Methods From August,2022 to April,2023,an online questionnaire survey was conducted among clinicians involved in end-stage patient management. Results A total of 205 questionnaires were distributed,with an effective response rate of 56.1%.Among the clinicians,55.7% of them had experience of applying sedation therapy in end-stage patients;85.2% of clinicians believed that sedation could relieve the suffering of terminal patients from physical refractory symptoms;75.7% of clinicians considered that sedation therapy could be used to relieve agony from psycho-existential distress.Most clinicians had concerns about sedation therapy due to the lack of legal support(86.1%)and the lack of understanding of patients or families(59.1%).The majority (90.4%) of clinicians were willing to receive training on palliative sedation. Conclusions A majority of clinicians agree that sedation therapy could relieve the physical distress and psycho-existential distress in end-stage patients.However,most clinicians have concerns about the application of sedation therapy due to the lack of legal support.It is necessary to enhance the training on palliative sedation.

End-stage patients experience unbearable pain because of refractory symptoms.Palliative sedation is a form of palliative care which relieves patients' agony by lowering their consciousness.Standard palliative sedation can help patients die with dignity.It is distinct from euthanasia and does not alter the survival of patients.Sufficient palliative care is the premise of palliative sedation.Repeated and detailed clinical evaluation,as well as multidisciplinary involvement,is necessary for the standardized implementation of palliative sedation.Here,we proposed the standard process and specifications of palliative sedation in Peking Union Medical College Hospital.Furthermore,we reported a case of palliative sedation for an advanced cancer patient with refractory delirium and living pain to demonstrate its application in clinical practice.

We provided the palliative care of a multiple disciplinary team care mode to a patient diagnosed with advanced head and neck cancer and her caregivers.People-centered integrated health services were provided according to the specific needs and preferences of individuals.The team-based palliative care relieved the suffering and improved the quality of life of the patient and that of her family who were facing challenges associated with life-threatening illness.

Objective: To investigate the effects of visual feedback training on knee function and balance ability in postoperative patients with knee fracture., Methods: A clinical randomized controlled trial with 104 participants, randomly assigned (1:1) to a visual feedback training group or a  control group. Eligible participants were evaluated using Lysholm scores, the Tinetti scale, and the evaluation module of TecnoBody® to demonstrate dynamic balance function in a standing position before treatment and after 4 and 8 weeks of treatment., Results: Both visual feedback training and control groups improved significantly in the Lysholm and Tinetti scores after 8 weeks. Compared with the control group, the TecnoBody® tests included centre of pressure path length, and the area over centre of pressure movement, both of which significantly improved in the visual feedback training group at 8 weeks after treatment. There was no difference between the 2 groups in terms of their Lysholm scores and Tinetti gait before the intervention and 4 weeks after treatment., Conclusion: Applying visual feedback training in conjunction with traditional rehabilitation strategies may improve knee function and motor control in postoperative patients with knee fracture. Although visual feedback training does not have a short-term effect on knee function and gait, this method could be a useful addition for rehabilitation of knee fracture patients.

Background: The main aim of this study was to demonstrate the antitumor potential of cucurbitacin A on A-549 NSCLC (non-small cell lung cancer cells). The effects of Cucurbitacin A on apoptotic induction, cell physic, cell cycle failure and m-TOR/PI3K/Akt signalling pathway were also investigated in the present study., Materials and Methods: MTT assay and clonogenic assay were carried out to study effects of this compound on cell cytotoxicity and colony forming tendency in A-549 cells. Moreover, phase and fluorescence microscopic techniques were used to examine the effects on cell morphology and induction of apoptosis. The effects on cell cycle phase distribution were investigated by flow cytometry and effects on m-TOR/PI3K/Akt signalling proteins were assessed by western blot analysis., Results: Results showed that cucurbitacin A induced dose-dependent cytotoxic effects along with suppressing the colony forming tendency in these cells. Cucurbitacin A also induced morphological changes in these cells featuring chromatin condensation, cell shrinkage and apoptotic body formation. G2/M phase cell cycle collapse was also induced by Cucurbitacin A along with inhibition of expression levels of m-TOR/PI3K/Akt proteins., Conclusions: In conclusion, cucurbitacin A inhibits cancer growth in A-549 NSCLC cells by inducing apoptosis, targeting m-TOR/PI3K/Akt signalling pathway and G2/M cell cycle., Competing Interests: Conflict of interest: The authors declare no conflict of interest

Background. CD8(+) T lymphocytes are known to play a critical role in the pathogenesis of chronic obstructive pulmonary disease (COPD). However, systematic analyses of CD8(+) T cell (Cytotoxic T cells, Tc) subsets in COPD patients have yet to be well conducted. Methods. The whole Tc subsets, including Tc1/2/10/17, CD8(+) regulatory T cells (Tregs) and CD8(+) α7(+) T cells, were quantified by flow cytometry in peripheral blood from 24 stable COPD subjects (SCOPD), 14 patients during acute exacerbations (AECOPD), and 14 healthy nonsmokers (HN). Results. Acute exacerbations of COPD were accompanied by elevated levels of circulating CD8(+) T cells. Tc1 cells were increased in both SCOPD and AECOPD patients, whereas the percentage of Tc2 cells was decreased in SCOPD patients but remained normal in AECOPD patients. Tc17 cells were increased only in AECOPD patients, and the percentage of Tc10 cells was reduced in both SCOPD and AECOPD patients. The imbalances of pro/anti-inflammatory Tc subsets observed in COPD may be caused by the lack of Tc10 cells and the impaired anti-inflammatory capacity of CD8(+) Tregs. Conclusions. The imbalances between subsets of CD8(+) peripheral blood T cells contribute to the immune response dysfunction in COPD pathogenesis.

Objective: Typical hemifacial spasm (HFS) commonly initiates from the orbicularis oculi muscle to the orbicularis oris muscle. Atypical HFS (AHFS) is different from typical HFS, in which the spasm of muscular orbicularis oris is the primary presenting symptom. The objective of this study was to analyze the sites of compression and the effectiveness of microvascular decompression (MVD) for AHFS., Methods: The authors retrospectively analyzed the clinical data for 12 consecutive patients who underwent MVD for AHFS between July 2008 and July 2013., Results: Postoperatively, complete remission of facial spasm was found in 10 of the 12 patients, which gradually disappeared after 2 months in 2 patients. No recurrence of spasm was observed during follow-up. Immediate postoperative facial paralysis accompanied by hearing loss occurred in 1 patient and temporary hearing loss with tinnitus in 2. All 3 patients with complications had gradual improvement during the follow-up period., Conclusions: The authors conclude that most cases of AHFS were caused by neurovascular compression on the posterior/rostral side of the facial nerve distal to the root entry zones. MVD is a safe treatment for AHFS, but the incidence of postoperative complications, such as facial paralysis and decrease in hearing, remains high.

Background: CD8+ T cells (Cytotoxic T cells, Tc) are known to play a critical role in the pathogenesis of smoking related airway inflammation including chronic obstructive pulmonary disease (COPD). However, how cigarette smoke directly impacts systematic CD8+ T cell and regulatory T cell (Treg) subsets, especially by modulating muscarinic acetylcholine receptors (MRs), has yet to be well elucidated., Methods: Circulating CD8+ Tc/Tregs in healthy nonsmokers (n = 15), healthy smokers (n = 15) and COPD patients (n = 18) were evaluated by flow cytometry after incubating with anti-CD3, anti-CD8, anti-CD25, anti-Foxp3 antibodies. Peripheral blood T cells (PBT cells) from healthy nonsmokers were cultured in the presence of cigarette smoke extract (CSE) alone or combined with MRs agonist/antagonist for 5 days. Proliferation and apoptosis were evaluated by flow cytometry using Ki-67/Annexin-V antibodies to measure the effects of CSE on the survival of CD8+ Tc/Tregs., Results: While COPD patients have elevated circulating percentage of CD8+ T cells, healthy smokers have higher frequency of CD8+ Tregs. Elevated percentages of CD8+ T cells correlated inversely with declined FEV1 in COPD. CSE promoted the proliferation and inhibited the apoptosis of CD8+ T cells, while facilitated both the proliferation and apoptosis of CD8+ Tregs. Notably, the effects of CSE on CD8+ Tc/Tregs can be mostly simulated or attenuated by muscarine and atropine, the MR agonist and antagonist, respectively. However, neither muscarine nor atropine influenced the apoptosis of CD8+ Tregs., Conclusion: The results imply that cigarette smoking likely facilitates a proinflammatory state in smokers, which is partially mediated by MR dysfunction. The MR antagonist may be a beneficial drug candidate for cigarette smoke-induced chronic airway inflammation.

Objective: To explore the relationship between contractile characteristics and fiber type conversion in hind-limb unloading mice soleus., Methods: After 28-day hind-limb unloading and muscle atrophy, we used the method of isolated muscle perfusion with different stimulated protocols to determine the changes in contractile characteristics including the isometric twitch force and tetanus force and fatigue index of slow twitch muscle in mice. The muscle myofibrillar composition and fiber type conversion were detected by immunofluorescence staining and real-time PCR., Results: The isometric twitch force and the tetanus force and fatigue index were decreased progressively in 28-day unloaded mice soleus, with the increase in fast twitch fiber subtype and the decrease in slow twitch fiber subtype., Conclusion: The alteration of contractile characteristics is relevant to the slow-to-fast fiber conversion in mice soleus after 28-day hind-limb unloading.

Objective: To investigate the molecular mechanisms underlying in the treatment of inflammatory bowel disease by Pulsatilla Decoction., Methods: Forty Wistar male rats were randomly divided into 5 groups( n = 8)control group, model group, model + positive control group (mesalazine), Pulsatilla Decoction treatment group, in addition, the Pulsatilla Decoction treatment group was divided into middle and high dose group. Intragastric administration was used in the positive control group and Pulsatilla Decoction treatment group. The expression of interleukin-1beta (IL-1beta), interleukin-6(IL-6) and tumor necrosis factor-alpha (TNF-alpha) were detected by real time PCR after extraction of RNA from colons., Results: Compared with the model group, positive medicine and Pulsatilla Decoction group, especially high-dose group, could effectively inhibit the expression of IL-1beta, IL-6 and TNF-alpha., Conclusion: Pulsatilla Decoction could exert its effect in the treatment of inflammatory bowel disease by inhibiting the expression of proinflammatory cytokines.

Objective: To investigate molecular mechanisms underlying in the treatment of inflammatory bowel disease by Pulsatilla decoction., Methods: Wistar male rats were randomly divided into control group, model group, model + positive control group (mesalazine), traditional Chinese medicine treatment group, in addition, the Chinese medical treatment group was divided into middle and high dose group ( n = 8). Intragastric administration was used in the positive control group and traditional Chinese medicine treatment group. The expression of Smad7 and p-Smad3 in the colons were detected by immunohistochemistry and Western blot., Results: Compared with the model group, positive medicine and traditional Chinese medicine group, especially high-dose group, could effectively inhibit the expression of Smad7, while enhancing the p-Smad3 expression., Conclusion: The activation of TGF-beta1/Smad3 signaling pathway may be the molecular mechanism underlying in the anti-inflammatory effect of inflammatory bowel disease by Pulsatilla decoction.

In order to provide basis for evaluating the effects of air pollutant such as O3 on crops yield and food security, the effects of O3 fumigation (ambient air, CK; 100 nL x L(-1), T1; 150 nL x L(-1), T2) on chlorophyll a fluorescence and gas exchange of a field-grown winter-wheat (Triticum aestivum L. Yang Mai 13) in different growing period were conducted via open-top chamber technique in conjunction with Diving-PAM fluorometer and LC pro + photosynthesis system. Results indicated that Fv/Fm caused by T1 was higher than 0.8, while the Pm, qP, (1-qP)/NPQ and Y(NO) were similar to those of CK, the NPQ and Y(NPQ) were increased by 13.5%-29.0% and 13.3%-22.7% respectively due to O3 stress. Under nature light (rapid light curve, RLC) and after dark adaptation (induction curve in steady-state, IC) the Yield of T1 was decreased by 4.6%-7.6% and 11.3%-19.3% respectively, with 8.0%-9.8% and 11.0%-23.1% reductions in Pn, and Gs compared to CK, respectively. In heading stage and blooming stage, the Ls of T, was greater than CK, but in filling stage and mature stage, it became lower compared to CK. The Fv/Fm was slightly lower than 0.8 under T2 treatment, with the Y(NO), (1-qP)/NPQ and c(i) were increased by 37.9%-75.6%, 157.1%-325.8% and 3.4%-18.1% relative to CK. Under RLC and IC condition, the Yield of T2 was respectively decreased by 10.2%-13.6% and 21.4%-29.1%, and the Pn, Ls, qP, Pm, NPQ and Y(NPQ) were decreased by 28.1%-39.9%, 5.2%-21.3%, 15.8%-30.4%, 27.6%-45.6%, 3.3%-52.9% and 5.7%-17.9% in comparison, respectively. Obviously the enhanced O3 causes a significant decrease in the capacity of photosynthesis of winter wheat, and the influence mechanism presents a series of dynamic changes according to growing seasons. The reduction of Fv/Fm under T1 treatment is a response of PS II reaction center to the increase of NPQ, and the decrease in Pn and Yield is a consequence of protective adjustment, by this approach, the antioxidant system and energy dissipation mechanism can thus prevent light damage to the PS II reaction center of winter wheat. Under T2 treatment, the CO2 assimilation and Q(A) re-oxidizing during actinic illumination are restricted, the energy dissipation mechanism was destroyed, and the reduction of photosynthesis was mainly due to damage in photosystem caused by O3 and excess light. The critical loads for O3 of PS II reaction center is between 100 nL x L(-1) and 150 nL x L(-1) close to 100 nL x L(-1). While the Fv/Fm value is not an effective index for assessing O3 influence on winter-wheat. Although the winter-wheat can have certain adapted ability to O3 stress, the growing enhancement of surface O3 is still a great threat to agricultural production in China.

Neurotransmitter release normally requires calcium triggering. However, the somata of dorsal root ganglion (DRG) neurons possess a calcium-independent but voltage-dependent secretion (CIVDS) in addition to the classic calcium-dependent secretion (CDS). Here, we investigated the physiological role of CIVDS and the contributions of CIVDS and CDS induced by action potentials (APs) in DRG soma. Using membrane capacitance measurements, caged calcium photolysis, and membrane capacitance kinetics analysis, we demonstrated that AP-induced secretion had both CIVDS and CDS components. Following physiological stimuli, the dominant component of AP-induced secretion was either CIVDS for spontaneous firing or CDS for high-intensity stimuli. AP frequency modulates CDS-coupled exocytosis and CIVDS-coupled endocytosis but not CIVDS-coupled exocytosis and CDS-coupled endocytosis. Finally, CIVDS did not contribute to excitatory postsynaptic currents induced by APs in DRG presynaptic terminals in the spinal cord. Thus, CIVDS is probably an essential physiological component of AP-induced secretion in the soma. These findings bring novel insights into primary sensory processes in DRG neurons.

Objective: To explore the anti-tumor immune responses of dendritic cells (DCs) loaded with intact wild-type p53 to mice challenged with tumor cells expressing p53 genes with mutations at different sites., Methods: Ad-p53-DC immunization function was assessed by the expression of surface molecules and allogeneic MLR. DCs derived from bone marrow were transduced with adenovirus or a human wild-type p53 containing recombinant adenovirus (Ad-DC and Ad-p53-DC) and immunized C57BL/6 mice. Splenocytes were separated and cell cytotoxicity was measured against tumor cells expressing mutant p53 (MethA, D459 and P815) in a standard 6-h(51)Cr-release assay. Effector and target cells were incubated in the presence of anti-CD(4) or anti-CD(8) antibody. Ad-p53-DC was immunized in control Ad-DC before or after mice were challenged with either D459 tumor or with MethA sarcoma cells to observe whether immune response would provide tumor protection., Results: Immunization with Ad-p53-DC developed significantly higher substantial CTL responses against Ad-p53-P815, D459 and MethA cells (effectors: target cells = 50:1), (27.8 +/- 3.4)%, (23.5 +/- 2.7)%, (58.3 +/- 9.2)% than with Ad-DC (9.3 +/- 1.8)%, (4.6 +/- 1.0)%, (23.5 +/- 3.7)% (t(d) = 5.79, 3.68, 5.02, all P < 0.05). In Ad-p53-DC immunized mice, anti-CD(8) antibody blocked the cytotoxicity against Ad-p53-P815 (26.7 +/- 2.8)% or D459 (6.1 +/- 1.2)%, but not anti-CD(4) antibody [(59.8 +/- 4.6)%, (18.9 +/- 2.4)%, t(d) = 8.79 or 9.18, all P < 0.05]. Ad-p53-DC immunization provided complete tumor protection in 80% of mice challenged with D459 and in 70% of mice challenged with MethA, while none protected in Ad-DC immunization group (chi(2) = 6.72, 5.86, all P < 0.05). Treated with Ad-p53-DC after D459 inoculation subcutaneously, mice were killed due to the bulky tumor more than 2 weeks later than the mice in the Ad-DC treatment group during 7 week observation (chi(2) = 9.48, P < 0.05)., Conclusion: DCs transfected with 100 MOI Ad-p53 induced intense CTL responses against P815, D459 and MethA. This CTL response is mediated by CD(8)(+) T cells. Treatment with Ad-p53-DC significantly developed tumor immunology and slowed the growth of established tumors.

Objective: To study on visible display of Meridian on the dummy human body., Methods: Tube model-building method and computer technique were used, and data came from Voxel-Man dummy human body development platform., Results: The visual effect of re-building Meridian is very good and it can display the different layers of anatomic structures on the Meridian lines., Conclusion: The visible display of Meridian on the dummy human body is preliminary realized, which provides data carriers for establishing the platform of Meridian study.

On the basis of the analysis of chemical components of the natural limestones from different deposits in China, the pore structures of the typical limestones, with the different CaCO3 content, were examined. The reactivity of the limestones was investigated by sulfuric acid titration and gas-liquid absorption methods. The research results showed that the specific surface area of the natural limestones studied in this work was about 1.8 m2/g. It was seen that the pH of the limestone slurry rapidly decreased and then back up when the sulfuric acid was added. The higher the CaCO3 content was, or the smaller the particle size was, the larger the pH back-up rate was, and similarly the faster the SO2 concentration of the reactor outlet increased. The Reactivity of the limestone obtained by the sulfuric acid titration had the same features as that obtained by the gas liquid absorption. Compared with the specific surface area, the CaCO3 content had more effect on the reactivity of the limestones. The particle size of the limestones had a significant effect on the reactivity when the particle size was relatively large, that is less than 300-360 mesh, vice versa.

Objective: To study the difference in the pharmacokinetics of emodin in Zhiganning capsules and Rhizoma Polygontum Cuspidatum by nonaqueous RP-HPLC., Method: The rats were orally administered with the extraction of Rhizoma Polygontum Cuspidatum and Zhiganning capsules. After hydrolysis and extraction, the content of emodin in the plasma is determined by Nonaqueous RP-HPLC., Result: The concentration-time profiles of emodin fit two-compartment model. The pharmacokinetics parameters including, t1/2alpha, AUC(0-infinity), CL(s) and C(max) of emodin in the group of Rhizoma Polygontum Cuspidatum were significantly different from these in the group of its compounds., Conclusion: There is a significant difference in pharmacokinetics of emodin between zhiganning capsules and the extraction of Rhizoma Polygontum Cuspidatum.