Effects of different precursors on the structure of lignin-based biochar and its ability to adsorb benzopyrene from sesame oil.

Agricultural by-products of sesame are promising bioresources in food processing. This study extracted lignin from the by-products of sesame oil production, namely, the capsules and straw of black and white sesame. Using acid, alkali, and ethanol methods, 12 distinct lignins were obtained to prepare biochar, aiming to investigate both the structural characteristics of lignin-based biochar (LBB) and its ability to remove benzo[a]pyrene (BaP) from sesame oil. The results showed that white sesame straw was the most suitable raw material for preparing biochar. In terms of the preparation method, acid-extracted lignin biochar was more effective in removing BaP than alkaline or ethanol methods. Notably, WS-1LB (white sesame straw acid-extracted lignin biochar) exhibited the highest BaP adsorption efficiency (91.44 %) and the maximum specific surface area (1065.8187 m2/g), characterized by porous structures. The pseudo 2nd and Freundlich models were found to be the best fit for the adsorption kinetics and isotherms of BaP on LBB, respectively, suggesting that a multilayer adsorption process was dominant. The high adsorption of LBB mainly resulted from pore filling. This study provides an economical and highly efficient biochar adsorbent for the removal of BaP in oil.

[Seasonal dynamics in photosynthetic characteristics and growth of Cunninghamia lanceolata saplings and their response to soil warming]. / æ‰æœ¨å¹¼æ ‘å ‰åˆç‰¹æ€§ä¸Žç”Ÿé•¿çš„å­£èŠ‚å˜åŒ–åŠå ¶å¯¹åœŸå£¤å¢žæ¸©çš„å“åº”.

In order to understand the response and adaptation mechanisms of photosynthetic characteristics and growth for Cunninghamia lanceolata saplings in the subtropical region to global warming, we conducted the root-box warming experiment (ambient, ambient+4 ℃) at the Sanming Forest Ecosystem National Observation and Research Station in Fujian Province to investigate the effects of soil warming on the photosynthetic characteristics and growth of C. lanceolata saplings in different seasons. The results showed that the net photosynthetic rate (Pn) and stomatal conductance (gs) of C. lanceolata significantly decreased in summer compared with in spring and autumn. Soil warming had no effect on the Pn and gs of C. lanceolata. However, the interaction between warming and season significantly impacted the leaf water use efficiency (WUE). The tree height and ground diameter growth of C. lanceolata significantly increased in spring compared with in summer and autumn. Warming significantly reduced ground diameter growth, and it diminished the net diameter growth by 48.1% in autumn. However, warming had no impact on the tree height growth of C. lanceolata in each season. The specific leaf area, soluble sugar, and non-structural carbohydrates contents of C. lanceolata significantly improved in summer and autumn compared with in spring. Warming had rarely influence on leaf functional traits in each season. In conclusion, the response of photosynthesis for C. lanceolata to soil warming was insignificant. The photosynthesis of C. lanceolata exhibited significant seasonal dynamics, primarily controlled by gs. C. lanceolata adapted to soil warming by adjusting WUE, and it adjusted to high temperatures and drought stress in summer by increasing soluble sugar content and specific leaf area. The effect of warming on ground diameter growth of C. lanceolata was primarily driven by soil moisture. The seasonal difference in the growth of C. lanceolata was influenced by the photosynthesis of C. lanceolata and the trade-off between the utilization and storage of photosynthetic products.

Acupuncture for cervical dystonia associated with anxiety and depression: A case report.

BACKGROUND: Cervical dystonia (CD) is a type of muscle tone disorder that usually occurs in the neck muscles. Due to the intermittent or continuous involuntary contraction of the neck muscles, the head and neck are twisted and skewed and some postural abnormalities occur. Long-term abnormal posture or pain can cause negative emotions in patients, which can affect their quality of life. CASE SUMMARY: This case report included a 37-year-old woman who was diagnosed with CD associated with anxiety and depression; the accompanying symptoms were head and neck tilt of approximately 90° to the right and mental abnormality. After two courses of acupuncture treatment, the patient's head and neck can be maintained in a normal position, and the negative emotions can be relieved. CONCLUSION: This case indicates that acupuncture can effectively improve CD and the emotional state and quality of life of patients, making it an effective alternative treatment for the condition.

CD38 Deficiency Alleviates Diabetic Cardiomyopathy by Coordinately Inhibiting Pyroptosis and Apoptosis.

Diabetic cardiomyopathy is one of the diabetes mellitus-induced cardiovascular complications that can result in heart failure in severe cases, which is characterized by cardiomyocyte apoptosis, local inflammation, oxidative stress, and myocardial fibrosis. CD38, a main hydrolase of NAD+ in mammals, plays an important role in various cardiovascular diseases, according to our previous studies. However, the role of CD38 in diabetes-induced cardiomyopathy is still unknown. Here, we report that global deletion of the CD38 gene significantly prevented diabetic cardiomyopathy induced by high-fat diet plus streptozotocin (STZ) injection in CD38 knockout (CD38-KO) mice. We observed that CD38 expression was up-regulated, whereas the expression of Sirt3 was down-regulated in the hearts of diabetic mice. CD38 deficiency significantly promoted glucose metabolism and improved cardiac functions, exemplified by increased left ventricular ejection fraction and fractional shortening. In addition, we observed that CD38 deficiency markedly decreased diabetes or high glucose and palmitic acid (HG + PA)-induced pyroptosis and apoptosis in CD38 knockout hearts or cardiomyocytes, respectively. Furthermore, we found that the expression levels of Sirt3, mainly located in mitochondria, and its target gene FOXO3a were increased in CD38-deficient hearts and cardiomyocytes with CD38 knockdown under diabetic induction conditions. In conclusion, we demonstrated that CD38 deficiency protected mice from diabetes-induced diabetic cardiomyopathy by reducing pyroptosis and apoptosis via activating NAD+/Sirt3/FOXO3a signaling pathways.

Methylation-Powered Assembly of a Single Quantum Dot-Based FRET Nanosensor for Antibody-Free and Enzyme-Free Monitoring of Locus-Specific N6-Methyladenosine in Clinical Tissues.

N6-Methyladenosine (m6A) is the most pervasive and evolutionarily conserved epitranscriptomic modification in long noncoding RNA (lncRNA), and its dysregulation may induce aberrant transcription and translation programs. Herein, we demonstrate the methylation-powered assembly of a single quantum dot (QD)-based fluorescence resonance energy transfer (FRET) nanosensor for antibody- and enzyme-free monitoring of locus-specific m6A in clinical tissues. The m6A-sensitive DNAzyme VMC10 is employed to identify a specific m6A site in lncRNA, and it catalyzes the hydrolytic cleavage of unmethylated lncRNA. The cleaved lncRNA fails to trigger the subsequent catalytic hairpin assembly (CHA) reaction due to the energy barrier. In contrast, when m6A-lncRNA is present, the methyl group in m6A protects lncRNA from VMC10-mediated cleavage. With the aid of an assistant probe, the retained intact m6A-lncRNA is released from the VMC10/lncRNA complex and subsequently triggers the CHA reaction, generating abundant AF647/biotin dual-labeled duplexes. The assembly of AF647/biotin dual-labeled duplexes onto 605QD results in efficient FRET between 605QD and AF647. The FRET signal can be simply quantified by single-molecule detection. Notably, this assay can be implemented in an antibody-free and enzyme-free manner. This nanosensor can sensitively quantify target m6A with a detection limit of 0.47 fM, and it can discriminate as low as a 0.001% m6A level from excess coexisting counterparts. Importantly, this nanosensor can monitor the cellular m6A level with single-cell sensitivity and profile target m6A expression in breast cancer and healthy para-cancerous tissues, providing a powerful tool for studying the physiological and pathological functions of m6A.

[Relationship between MTHFR Gene Polymorphism(C677T) and Adverse Reactions of High-Dose Methotrexate in Pediatric Patients with Acute Lymphoblastic Leukemia].

OBJECTIVE: To explore the effects of methylenetetrahydrofolate reductase (MTHFR) C677T gene polymorphism on the adverse reactions of high-dose methotrexate (MTX) in pediatric patients with acute lymphoblastic leukemia (ALL). METHODS: A total of 69 children with ALL admitted to the department of Pediatrics of Sun Yat-sen Memorial Hospital of Sun Yat-sen University from November 2018 to October 2020 were included in this study. The clinical data of the children were collected, leukocytes were isolated from their peripheral blood, and MTHFR genotyping was performed by digital fluorescence molecular hybridization techniques. The adverse reactions and plasma drug concentration of MTX were monitored during the chemotherapy. Moreover, the effect of MTHFR gene polymorphism on MTX adverse reactions and plasma drug concentration were analyzed. RESULTS: Among the middle and high risk children, compared with the wildtype group (CC genotype), patients with MTHFR C677T mutations (CT+TT genotypes) had a higher risk of leukopenia (OR=2.38), neutropenia (OR=2.2), anemia (OR=1.83) and hepatoxicity (OR=1.98). However, no significant difference was found in the MTX plasma concentration between the MTHFR C677T mutantion group and the wildtype group at different timepoints (24 h, 48 h and 72 h). Multivariate analysis revealed that the plasma concentration of MTX (48 h), clinical risk level of ALL and MTHFR C677T gene polymorphism were independent factors for the adverse reactions of high-dose MTX. CONCLUSION: The MTHFR C677T mutations may be associated with myelosuppression and hepatotoxicity in children with ALL after high-dose MTX treatment.

["Huayu Tongluo" moxibustion improves learning-memory ability and promotes myelin regeneration by regulating Sonic Hedgehog signaling pathway in vascular dementia rats].

OBJECTIVE: To investigate the effect of "Huayu Tongluo" (resolving blood stagnation to dredge meridian-collaterals) moxibustion on remyelination and Sonic Hedgehog (Shh) signaling pathway in the corpus callosum of vascular dementia (VD) rats, so as to explore its mechanisms underlying improvement of VD. METHODS: Male Wistar rats were randomized into sham-operation, model, medication and moxibustion groups, with 12 rats in each group.The VD model was established by bilateral common carotid artery occlusion. Moxibustion was applied to "Shenting"(GV24), "Baihui"(GV20) and "Dazhui"(GV14) for 20 min once a day, 7 d as a treatment course, for 3 courses, with one day's rest between every two courses. Rats of the medication group were treated by gavage of 10 mg/kg of chloromastine solution once a day, and the course of treatment was the same as that of the moxibustion group. The rat's learning-memory ability was assessed by Morris water maze test (escape latency). The neurological deficits were evaluated by using Longa's scale.The mRNA and protein expressions of Shh and Gli1 in the corpus callosum were measured by quantitative real-time fluorescence PCR and Western blot, separately. The ultrastructure of the myelin sheath and myelinated axons was observed under transmission electron microscopy (TCM). RESULTS: Compared with the sham-operation group, the neurologic score and escape latency were significantly increased and prolonged (P<0.01), and the mRNA and protein expression levels of Shh and Gli1 and the number of myelinated axons were obviously decreased in the model group (P<0.01). In comparison with the model group, the escape latency was apparently shortened (P<0.05), while the mRNA and protein expression levels of Shh and Gli1 as well as the number of myelinated axons were strikingly increased in both moxibustion and medication groups (P<0.01). Results of TCM showed that in the model group, the arrangement of myelin coil structures was sparse and fuzzy, and some structures were bulged and disbanded. The oligodendrocytes were irregular, and the number of myelin sheath was rare. These situations were relatively milder in both moxibustion and medication groups. CONCLUSION: "Huayu Tongluo" moxibustion can promote the differentiation and maturation of oligodendrocyte precursor cells after cerebral ischemia by regulating the expressions of Shh and Gli1 in Shh signaling pathway, thus promoting the regeneration of cerebral white matter myelin sheaths in VD rats, which may contribute to improving learning-memory ability.

Chidamide as maintenance after chemotherapy or hematopoietic stem cell transplantation in 27 children with T-cell lymphoblastic leukemia: A real-world prospective study.

Background: The long-term overall survival of children with T-cell acute lymphoblastic leukemia (T-ALL) is limited to approximately 80-85% because of a high incidence of relapse after achieving remission with intensive chemotherapy and hematopoietic stem cell transplantation (HSCT). Novel treatment strategies inducing long-term remission are needed to improve the outcome. Histone deacetylase inhibitors (HDACis) have been reported to be effective in a series of T-ALL cases. Preclinical studies suggested that T-ALL cells are sensitive to Chidamide, which is a selective HDACi. Methods: This preliminary clinical study evaluated the efficacy and safety of Chidamide in combination with chemotherapy or post-HSCT for children with T-ALL at a dose of 0.5 mg/kg weight of patient twice per week for at least 6 months. Results: In total, 27 children with a mean age of 7.88 years were included. The high-risk proportion was 66.7%. After a median follow-up period of 37.8 months (9.5-67.9 months), the overall survival and event-free survival in the patients treated with Chidamide were 94.1 and 95.2%, respectively. All patients except two maintained persistent remission with <0.01% blast cells in minimal residual disease. Conclusion: The combination therapy with Chidamide in a case series of T-ALL shows the promising clinical efficacy and good safety in children. Clinical trial registration: https://www.chictr.org.cn/, identifier ChiCTR2000030357.

Controllable atomic collision in a tight optical dipole trap.

Single atoms are interesting candidates for studying quantum optics and quantum information processing. Recently, trapping and manipulation of single atoms using tight optical dipole traps has generated considerable interest. Here we report an experimental investigation of the dynamics of atoms in a modified optical dipole trap with a backward propagating dipole trap beam, where a change in the two-atom collision rate by six times has been achieved. The theoretical model presented gives a prediction of high probabilities of few-atom loading rates under proper experimental conditions. This work provides an alternative approach to the control of the few-atom dynamics in a dipole trap and the study of the collective quantum optical effects of a few atoms.

Effectiveness of resilience-promoting interventions in adolescents with diabetes mellitus: a systematic review and meta-analysis.

BACKGROUND: This study aimed to analyze the efficacy of resilience-promoting interventions among adolescents and youth aged 10-24 years with any type of diabetes. METHODS: A systematic literature search was performed using the PubMed, Web of Science, Embase, Cochrane Library, CINAHL, and PsycINFO databases from inception to May 25, 2022. The Cochrane risk of bias tool (version 2) was used to assess the quality of the included studies. A meta-analysis was performed to calculate the pooled effects of resilience-promoting interventions. RESULTS: Nineteen articles were included covering an overall sample of 2048 adolescents with diabetes. When analyzing the effectiveness of resilience-promoting interventions, hemoglobin A1c (HbA1c) at six months [mean difference = - 0.47, 95% confidence interval (CI) = - 0.83 to - 0.12, P = 0.009] after the intervention was improved. However, long-term (≥ 12 months) improvement in HbA1c was not significant. In addition, comparing the control group, there were significant differences in the effect size for stress [standardized mean difference (SMD) = - 0.87, 95% CI = - 1.25 to -0.48, P < 0.05], self-efficacy (SMD = 0.50, 95% CI = 0.02-0.98, P = 0.04) and quality of life (SMD = 0.27, 95% CI = 0.03-0.51, P = 0.03). CONCLUSIONS: Resilience-promoting intervention is a promising way for adolescent diabetes management to improve HbA1c, stress, self-efficacy, and quality of life. Incorporating resilience-promoting components into diabetes education and re-enforcing these contents every six months are recommended for implementation in clinical practice.

An entropy-driven three-dimensional multipedal-DNA walker for ultrasensitive detection of cancer cells.

Sensitive and accurate detection of cancer cells is of great significance for the early diagnosis and treatment of cancer. In this work, we developed a simple fluorescent signal amplification biosensor based on an entropy-driven three-dimensional (3D) multipedal-DNA walker for highly sensitive detection of cancer cells. Firstly, DNA tetrahedron nanostructures (DTNs) combined with AS1411 aptamer were used as the capture probe to achieve efficient capture of cancer cells. Then, the bipedal hairpin fuel chain hybridized with DTNs and exposed two catalytic "legs" to form a walker probe. Finally, the walker probe autonomously walked on polystyrene microspheres (PS) via entropy-driven catalytic reaction. DTNs rolled on the PS to achieve multipedal walking, realizing fluorescence signal amplification due to fluorescence recovery of DNA-CdTe quantum dots on the PS surface. This fluorescence signal amplification strategy showed excellent selectivity and sensitivity toward cancer cells with the detection limit of 7 cell mL-1. This entropy-driven 3D multipedal DNA walker fluorescence exhibited great potential in detecting circulating tumor cells and tumor markers used for early diagnosis and clinical treatment of cancer.

Aptamer-mediated DNA concatemer functionalized magnetic nanoparticles for reversible capture and release of circulating tumor cells.

Effectively capturing, releasing, and reanalyzing circulating tumor cells (CTCs) are critical in cancer diagnosis and individualized treatment. Traditional immunomagnetic separation has disadvantages of low sensitivity and specificity, and is time-consuming and costly in CTCs capture. It is also easily disturbed by the microenvironment in releasing and analyzing CTCs. Here, we proposed an aptamer-mediated DNA concatemer functionalized magnetic nanoparticles (MNPs-AMDC) for the reversible capture and release of CTCs. In this study, aptamers were used both for efficiently capturing CTCs without complicated assembly steps and stimulus-response switch for releasing CTCs with little influence on cellular activity. The MNPs-AMDC was demonstrated to effectively capture (83%) and release CTCs with a good viability rate (92%). Moreover, this device was also tested in clinical blood samples, which would provide a universal tool for diagnosing cancer and treating individuals.

[Efficacy of Posaconazole for Primary Prophylaxis in the Induction Therapy of Childhood Acute Lymphoblastic Leukemia].

OBJECTIVE: To explore the effect of posaconazole in the primary prevention of invasive fungal disease (IFD) in the induction therapy of childhood acute lymphoblastic leukemia (ALL). METHODS: From August 2018 to November 2020, 144 pediatric patients with ALL treated in Department of Pediatrics, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University were selected, 88 cases received fluconazole as IFD prophylaxis (fluconazole prophylaxis group), 56 cases received posaconazole as IFD prophylaxis (posaconazole prophylaxis group). The incidence of IFD and treatment-related adverse reactions between the two groups were compared, and the safety of posaconazole was evaluated. RESULTS: The incidence of IFD in the fluconazole prophylaxis group was 20.4% (18/88), and in the posaconazole prophylaxis group was 7.1% (4/56). The incidence of IFD between the two groups was statistically significant different(P=0.030). There was no serious adverse reactions in the two groups. The incidence of mild adverse reactions in the posaconazole prophylaxis group (23.2%) was lower than that in the fluconazole prophylaxis group(39.8%), and the difference was statistically significant (P=0.039). There were 12 cases died in the fluconazole prophylaxis group and 4 in the posaconazole prophylaxis group, while no significant difference in the overall survival rate between the two groups (P=0.281). CONCLUSION: The effect of posaconazole in the primary prophylaxis of IFD is better and incidence of adverse reactions is lower than fluconazole. Posaconazole can be tolerated, and expected to become the first-line primary prophylaxis drug for IFD during the induction remission therapy of childhood ALL.

[Roles of processing and compatibility in antidepression of Sini Powder:a metabonomics study].

The antidepressant mechanism of Sini Powder was investigated by metabonomics based on UHPLC-Q-TOF-MS, and the roles of processing and compatibility in the antidepression of Sini Powder were discussed in the present study. The chronic unpredictable mild stress(CUMS) model of depression was induced in the model group, the Bupleuri Radix group, the Paeoniae Radix Alba group, the herb-pair group(Bupleuri Radix-Paeoniae Radix Alba), the Sini Powder group, and the vinegar-processed Sini Powder group(Bupleuri Radix and Paeoniae Radix Alba were vinegar-processed). After the establishment of the model, the rats in each group were continuously administered with corresponding drugs(ig) at a dose of 9.6 g·kg~(-1) for eight days [the rats in the model group and the normal group(without model induction) received the same volume of normal saline at the same time]. Following the last administration, the differential metabolites were identified to analyze metabolic pathways based on the rat plasma samples collected from each group. A total of sixteen potential biomarkers were identified. The metabolites with significant changes were involved in many biological metabolic pathways, such as amino acid metabolism, pentose phosphate pathway, glycerol phospholipid metabolism, sphingolipid metabolism, and purine metabolism. After drug intervention, some biomarkers returned to normal levels. Further comparisons of processing and compatibility revealed that the vinegar-processed Sini Powder group had the most total metabolic pathways where differential metabolites were returned to normal. Compared with the individual herbs, the herb-pair significantly improved the recovery of differential metabolites in the pentose phosphate and purine metabolic pathways. Compared with the Sini Powder, the vinegar-processed Sini Powder facilitated the recovery of differential metabolites in the arginine biosynthesis, and pyrimidine and pentose phosphate metabolic pathways. As indicated by the results, Sini Powder may interfere with depression by regulating lipid and nucleotide metabolisms. The processing and compatibility of Chinese herbal medicines can potentiate the intervention on depression by regulating nucleotide, energy, and amino acid metabolisms to a certain extent.

[Effect of electroacupuncture preconditioning on neuronal activities in lateral hypothalamus area of myocardial ischemia reperfusion injury rats].

OBJECTIVE: To observe the effect of electroacupuncture (EA) preconditioning of "Shenmen" (HT7)-"Tongli" (HT5) segment of the Heart Meridian on neuronal electrical activities of lateral hypothalamus area (LHA) in rats with myocardial ischemia reperfusion injury (MIRI), so as to investigate its possible mechanism underlying improvement of MIRI. METHODS: Twenty-four SD rats were randomly divided into sham, model, EA and damage + EA (D+EA) groups, with 6 rats in each group. The MIRI model was established by occlusion of the anterior descending branch (ADB) of the left coronary artery for 30 min, followed by reperfusion for 2 h. In the sham operation group, the ADB was only threaded beneath the artery without ligation. EA (2 Hz, 1 V) was applied to bilateral HT7-HT5 for 20 min, once daily for 7 days. In the D+EA group, FN was injected with 0.4 µL of 1 g/L kainic acid solution. Electrocardiogram (ECG) of the neck-thoracic lead was recorded by using PowerLab. The electrical activities of the LHA region were recorded by the implanted microelectrode array (2×4) and Plexon multi-channel acquisition system. Cluster analysis of neuronal signals was carried out by Offline Sorter software. The discharge waveforms, autocorrelation and cross-correlation of neuronal activities were analyzed by using Neuro Explorer software. RESULTS: Compared with the sham group, the ECG-ST height was significantly increased (P<0.05), the discharge frequency of pyramidal neurons was significantly reduced (P<0.01), while the discharge frequency of interneurons was increased (P<0.01) in the model group. After EA treatment, the ECG-ST height was significantly decreased (P<0.05), the discharge frequency of pyramidal neurons was significantly increased (P<0.01) relevant to the model group. In comparison with the EA group, the ECG-ST height in the D+EA group was significantly elevated (P<0.05), whereas the discharge frequency of pyramidal neurons was significantly decreased (P<0.01). The discharge frequency of interneurons was kept increasing after MIRI. Real-time spectrum analysis showed that the local field potential spectrum energy of the EA group was significantly lower than that of the model group and the D+EA group. CONCLUSION: EA preconditioning of Heart Meridian can significantly increase the discharge frequency of LHA excitatory pyramidal neurons and reduce the energy of the local field potential spectrum, which maybe one of the important mechanisms of EA in anti -MIRI.

Multichannel left-subtract-right feature vector piston error detection method based on a convolutional neural network.

To realize the large-scale and high-precision co-phasing adjustment of synthetic-aperture telescopes, we propose a multichannel left-subtract-right feature vector piston error detection method based on a convolutional neural network, which inherits the high precision and strong noise resistance of the DFA-LSR method while achieving a detection range of (-139λ, 139λ) (λ = 720 nm). In addition, a scheme to build large training datasets was proposed to solve the difficulty in collecting datasets using traditional neural network methods. Finally, simulations verified that this method can guarantee at least 94.96% accuracy with large samples, obtaining a root mean square error of 10.2 nm when the signal-to-noise ratio is 15.

[Effect of electroacupuncture preconditioning on the contents of dopamine and 5-hydroxytryptamine in lateral hypothalamus area and cerebellar fastigial nucleus of rats with myocardial ischemia-reperfusion injury].

OBJECTIVE: To observe the effect of electroacupuncture (EA) preconditioning at heart meridian acupoints on the contents of dopamine (DA) and 5-hydroxytryptamine (5-HT) in lateral hypothalamus area (LHA) and cerebellar fastigial nucleus (FN) in the rats with acute myocardial ischemia-reperfusion injury (MIRI), and explore the role and mechanism of LHA and FN in the effect of EA at heart meridian acupoints against acute MIRI. METHODS: Sixty SD rats were randomly divided into a sham-operation group, a model group, an EA heart meridian group and an EA lung meridian group, 12 rats in each group, as well as an LHA plus heart meridian group (damage of bilateral LHA) and an FN plus heart meridian group (damage of bilateral FN), 6 rats in each one. Three days after nucleus destruction, EA was applied to "Shenmen" (HT 7) and "Tongli" (HT 5) in the EA heart meridian group, the LHA plus heart meridian group and the FN plus heart meridian group and EA was applied to "Taiyuan" (LU 9) and "Lieque" (LU 7) in the EA lung meridian group, with 1 V in stimulating voltage and 2 Hz in frequency, lasting 20 minutes each time, once a day, for consecutively 7 days before model replication. Except in the sham-operation group, MIRI rat models were duplicated by ligation of the left anterior descending branch of the coronary artery in the rest groups. Using Power lab physiological recorder, ST segment displacement value was recorded before modeling, 30 min after ligation and 120 min after reperfusion separately. The high performance liquid chromatography-electrochemical detection and analysis system was adopted to determine the contents of DA and 5-HT in LHA and FN dialysate after rat modeling in each group. RESULTS: In comparison of ST segment displacement value 30 min after ligation and 120 min after reperfusion among groups, the value in the model group was higher than that in the sham-operation group (P<0.01), those in the EA heart meridian group, the LHA plus heart meridian group, the FN plus heart meridian group and the EA lung meridian group were lower than those in the model group successively (P<0.01) and those in the EA heart meridian group were lower than those in the EA lung meridian group, the LHA plus heart meridian group and the FN plus heart meridian group successively (P<0.01). The contents of DA and 5-HT in FN and LHA in the model group were lower than those in the sham-operation group (P<0.01). Except in the groups with nucleus lesions, the contents of DA and 5-HT in FN and LHA of each intervention group were higher than those in the model group (P<0.01), the contents of DA and 5-HT in FN in the EA heart meridian group were higher than those in the EA lung meridian group and the LHA plus heart meridian group (P<0.01) and the content of 5-HT in LHA was higher than those in the EA lung meridian group and the FN plus heart meridian group (P<0.01) separately, the content of DA in LHA was higher than that in the EA lung meridian group (P<0.01). CONCLUSION: EA preconditioning at heart meridian acupoints can effectively alleviate myocardial injury in acute MIRI rats, during which, DA and 5-HT in LHA and FN may be the important material basis.

Construction of PD1/CD28 chimeric-switch receptor enhances anti-tumor ability of c-Met CAR-T in gastric cancer.

Chimeric antigen receptor (CAR) T cell is a promising method in cancer immunotherapy but faces many challenges in solid tumors. One of the major problems was immunosuppression caused by PD-1. In our study, the expression of c-Met in GC was analyzed from TCGA datasets, GC tissues, and cell lines. The c-Met CAR was a second-generation CAR with 4-1BB, cMet-PD1/CD28 CAR was c-Met CAR adding PD1/CD28 chimeric-switch receptor (CSR). In vitro, we measured the changes of different subgroups, phenotypes and PD-1 expression in CAR-T cells. We detected the secretion levels of different cytokines and the killing ability of CAR-Ts. In vivo, we established a xenograft GC model and observed the anti-tumor effect and off-target toxicity of different CAR-Ts. We find that the expression of c-Met was increased in GC. CD3+CD8+ T cells and CD62L+CCR7+ central memory T cells (TCM) were increased in two CAR-Ts. The stimulation of target cells could promote the expression of PD-1 in c-Met CAR-T. Compared with Mock T, the secretion of cytokines as IFN-γ, TNF-α, IL-6, IL-10 secreted by two CAR-Ts was increased, and the killing ability to c-Met positive GC cells was enhanced. The PD1/CD28 CSR could further enhance the killing ability, especially the long-term anti-tumor effect of c-Met CAR-T, and reduce the release level of IL-6. CAR-Ts target c-Met had no obvious off-target toxicity to normal organs. Thus, the PD1/CD28 CSR could further enhance the anti-tumor ability of c-Met CAR-T, and provides a promising design strategy to improve the efficacy of CAR-T in GC.

A Potential Predictive Biomarker for Miller/Payne Grading: PD-L1 Expression before Neoadjuvant Chemotherapy in Breast Cancer.

BACKGROUND AND OBJECTIVE: The aim of this study was to investigate the value of programmed death ligand 1 (PD-L1) expression as a predictive biomarker for Miller/Payne grading before neoadjuvant chemotherapy (NACT) in breast cancer. PATIENTS AND METHODS: The expression of PD-L1 in pretreatment biopsies of breast cancer was assessed by immunohistochemistry in tissue microarrays. The results were analyzed using SPSS 22.0 statistical software. RESULTS: Of 53 female patients, 10 (18.9%) patients had a grade 5 (G5) response, and 12 (22.6%) patients showed PD-L1 expression, including 7 (13.2%) patients with staining in tumor cells (TCs) and 8 (15.1%) patients with staining in peritumoral lymphocytes (PTLCs). Logistic regression analysis revealed that G5 response to NACT was significantly associated with TCs or PTLCs PD-L1 positivity, whether with univariate analysis (TCs PD-L1: p = 0.00, OR 20.50, 95% CI 3.11-134.94; PTLCs PD-L1: p = 0.02, OR 6.50, 95% CI 1.27-33.20) or with multivariate analysis (TCs PD-L1: p = 0.00, OR 42.23, 95% CI 3.36-530.90; PTLCs PD-L1: p = 0.02, OR 9.07, 95% CI 1.37-60.02). The same trend was found in the luminal subgroup analysis (TCs PD-L1: p = 0.02, OR 23.43, 95% CI 1.66-331.58; PTLCs PD-L1: p = 0.01, OR 47.89, 95% CI 2.47-927.41). CONCLUSION: G5 response to NACT in breast cancer was significantly associated with TCs or PTLCs PD-L1-positive expression in pretreatment biopsies; it can be expected that PD-L1 will become a new independent biomarker of response to NACT in breast cancer.

The Prognostic Value of Deficient Mismatch Repair in Stage II-IVa Nasopharyngeal Carcinoma in the Era of IMRT.

In the era of intensity-modulated radiotherapy (IMRT), it is important to analyse the prognostic value of deficient mismatch repair (dMMR) in nasopharyngeal carcinoma (NPC). In this study, in pretreatment biopsies of 69 patients with stage II-IVa NPC, the expression levels of MMR proteins, including MLH1, MSH2, MSH6 and PMS2, were assessed by immunohistochemistry (IHC). The median follow-up time was 37.5 months (3.1-87.4 months). 50.7% of cases (35/69) showed preserved expression of all 4 MMR proteins, which was interpreted as proficient mismatch repair (pMMR). Only 1.5% of cases (1/69) lost expression of all 4 MMR proteins, 26.1% of cases (18/69) have PMS2 loss alone and 21.7% of cases (15/69) lost expression of both PMS2 and MLH1. Thus, 49.3% of cases (34/69) lost expression of one or more MMR proteins, which was interpreted as dMMR. There was no significant difference (P > 0.05) in terms of sex, age, clinical stage, T category, N category or therapy regimens between the dMMR and pMMR groups. The multivariate Cox regression analysis revealed that dMMR was an independent significant prognostic factor for distant metastasis-free survival (DMFS) (dMMR vs pMMR: P = 0.01, HR = 0.25, 95% CI: 0.09~0.75). Therefore, NPC patients with dMMR had significantly superior DMFS compared with patients with pMMR. It can be expected that dMMR will become a new independent prognostic factor for NPC.