Cold and Heat in Acute Coronary Syndrome： A Review / 中国实验方剂学杂志

Cold and heat belong to the eight-principal syndrome differentiation of traditional Chinese medicine， which can reflect the rise and fall of Yin and Yang in the body and the Yin and Yang nature of the disease. At present， traditional Chinese medicine has an inconsistent understanding of cold and heat in acute coronary syndrome. The emphasis on pathogenic factors of cold and heat is biased， and the elements of cold and heat syndrome are not fully reflected in the scale. Therefore， the literature has been reviewed from the perspectives of etiology， pathogenesis， symptom elements， and test signs with drugs. From the perspective of etiology， both cold evil and heat evil can increase the risk of acute coronary syndrome. It was previously believed that acute coronary syndrome occurs frequently in cold climates such as winter and spring. Based on this understanding， hot weather can also induce acute coronary syndrome， and different temperatures have different effects on patients of different ages and with different underlying diseases. In addition， artificial pathogenic factors such as excessive consumption of cold food and refrigeration air conditioners were added. From the perspective of pathogenesis， on the basis of the traditional ''asthenia in origin and asthenia in superficiality'' and ''phlegm stagnation''， it is found that Yin-cold and fire-heat can both cause paralysis of the heart chakra and pain induced by the blockage. The pathogenesis of acute coronary syndrome characterized by heat stagnation and coldness featuring heartburn should be distinguished from gastroesophageal reflux disease. Moreover， the pathogenesis of Yin cold coagulation and pulse stagnation and wind obstruction are different. The acute coronary syndrome is in line with the wind characteristics of frequent changes and can be treated with wind medicine. From the perspective of syndrome elements， the syndrome elements such as cold condensation， heat accumulation， and toxicity are analyzed， and the use of basic syndrome elements and their combination forms facilitates clinical and scientific research. In addition， according to the test sign with the drug， it can be seen that the attributes of cold and heat of traditional Chinese medicine prescriptions for acute coronary syndrome can be explained according to the temperature-sensitive transient receptor potential （TRP） ion channel， thus proving the pathogenesis of cold and heat of acute coronary syndrome.

Systematic characterization and identification of the chemical constituents of the Schisandra chinensis decoction based on a hybrid scanning technique of UHPLC/IM-QTOF-MS / 药学学报

italic>Schisandra chinensis is a traditional Chinese medicine with the functions of reinforcing deficiency, strengthening, and inducing astringency, appliable to treat the chronic cough and deficiency in breath, palpitation, and insomnia, etc. A hybrid mass spectrometry scanning strategy (high-definition data-independent/data-dependent acquisition, HDDIDDA), enabling the ion mobility separation and alternating data-independent acquisition/data-dependent acquisition, was established, which, in combination with in-house library-driven automatic peak annotation workflows facilitated by the UNIFI software, was utilized to systematically characterize the multi-classes of chemical components from S. chinensis. The use of an HSS T3 column (100 mm × 2.1 mm, 1.8 μm), 0.1% formic acid in H2O-acetonitrile as the mobile phase running at the flow rate of 0.3 mL·min-1, and column temperature at 35 ℃, could enable good separation of the S. chinensis components within 42 min. HDDIDDA scan in both the positive and negative ion modes was employed for data acquisition. Based on the automatic peak annotation, reference standards comparison, MS2 data interpretation, and literature analysis, we were able to identify or tentatively characterize 105 compounds in the S. chinensis decoction, involving 56 terpenoids, 42 lignans, five glycosides, one organic acid, and one flavonoid. HDDIDDA scanning can improve the coverage of data acquisition and improve the accuracy of identification, while CCS prediction analysis provides the possibility to distinguish isomers by the ion mobility technology. The results provide reference for the intelligent material basis research of TCM.

Resistance to deltamethrin and its association with mutation sites in the sodium iron channel domain III gene in Rhipicephalus microplus in Huaihua City of Hunan Province / 中国血吸虫病防治杂志

Objective To investigate the level of deltamethrin resistance and mutation sites in the sodium iron channel gene in Rhipicephalus microplus in Huaihua City, Hunan Province, and to examine the correlation between deltamethrin resistance and mutation sites in the sodium iron channel gene in Rh. microplus. Methods Rh. microplus was sampled from multiple yellow cattle farms in Huaihua City, Hunan Province from June to September 2022, and the level of resistance to deltamethrin was determined in ticks using the adult immersion test. The sodium iron channel domain III gene was amplified in deltamethrin-resistant and wild-type Rh. microplus using PCR assay. Following sequencing and sequence alignment, mutation sites were detected in bases. The sodium iron channel domain III gene in Rh. microplus was translated, and the signal peptide, transmembrane domain, and phosphorylation and glycosylation sites were detected in amino acid sequences. The tertiary structures of the sodium iron channel domain III protein of deltamethrin-resistant and wild-type Rh. microplus were deduced and compared, and the association be tween mutation sites in bases and resistance to deltamethrin was examined in Rh. microplus according the level of deltamethrin resistance, sequence alignment and protein tertiary structure. Results The median (LC50) and 95% lethal concentrations (LC95) of deltamethrin were 121.39 mg/L and 952.61 mg/L against Rh. microplus, with a resistance factor of 9.24 and level II resistance. The sequence of the sodium ion channel domain III gene was 1 010 bp in size, and mutation sites were detected in two neighboring bases in the sequence of the sodium ion channel domain III gene in deltamethrin-resistant Rh. microplus. Although no signal peptides were found in the sodium iron channel domain III protein of deltamethrin-resistant or wild-type Rh. microplus, 6 trans-membrane domains, 42 phosphorylation sites and 8 glycosylation sites were identified, with a significant difference in the tertiary structure of the sodium iron channel domain III protein between deltamethrin-resistant and wild-type Rh. microplus. Conclusions Level II resistance to deltamethrin is detected in Rh. microplus in Huaihua City, Hunan Province, and two mutation sites that correlate with the emergence of deltamethrin resistance are identified in the sequence of the sodium iron channel domain III gene in deltamethrin-resistant Rh. microplus.

O pH da região vulvar no ciclo vital: revisão de escopo / The pH of the vulvar region in the life cycle: scoping review / El pH de la región vulvar en el ciclo vital: revisión del alcance

Introdução: mapear os estudos que mensuraram o potencial Hidrogeniônico (pH) da região vulvar no ciclo vital da mulher. Métodos: revisão de escopo conforme recomendações do Manual for Evidence Synthesis do Joanna Briggs Institute (JBI), nas bases SCOPUS, Web of Science, Academic Search Premier, PubMed, Bielefeld Academic Search Engine e Google Acadêmico em janeiro de 2022. Foram incluídos estudos publicados em português, espanhol, francês e inglês, sem limite temporal. Resultados: dos 954 documentos recuperados, 13 foram selecionados. Apurou- se que os estudos utilizaram diferentes procedimentos para as medições quanto aos equipamentos, ambiente e preparo das participantes. A média de idade apresentada pela população feminina estudada variou entre 31 e 43 anos. Os locais de medição vulvar foram os grandes e pequenos lábios, dobra interlabial e períneo. O menor valor do pH aferido foi 4,6 e o maior 6,3. Conclusões: constatou-se baixa produção de estudos acerca do pH vulvar e ênfase das pesquisas na população de mulheres adultas. A diversidade de procedimentos e locais de aferição encontrados não permite afirmações seguras sobre uma faixa de valor de pH da superfície da pele vulvar.

Introduction: to map the studies that measured the Potential of Hydrogen (pH) of the vulvar region in women's life cycle. Methods: scoping review according to recommendations from the Joanna Briggs Institute (JBI) Manual for Evidence Synthesis in the SCOPUS, Web of Science, Academic Search Premier, PubMed, Bielefeld Academic Search Engine and Google Scholar databases in January 2022. Studies published in Portuguese, Spanish, French, and English, without time limit, were included. Results: of the 954 documents retrieved, 13 were selected. Different measurement procedures in relation to equipment, environment and preparation of participants were used in the studies. The average age of the female population ranged between 31 and 43 years. The vulvar measurement sites were the labia majora and minora, interlabial sulci and perineum. The lowest pH value measured was 4.6 and the highest was 6.3. Conclusions: there was a low production of studies on vulvar pH and an emphasis of studies on the population of adult women. The diversity of procedures and measurement sites found does not allow for safe statements about a range of pH values on the surface of the vulvar skin.

Introducción: mapear los estudios que midieron el Potencial de Hidrógeno (pH) de la región vulvar en el ciclo vital de las mujeres. Métodos: revisión del alcance según las recomendaciones del Manual for Evidence Synthesis del Joanna Briggs Institute (JBI), en las bases de datos SCOPUS, Web of Science, Academic Search Premier, PubMed, Bielefeld Academic Search Engine y Google Scholar en enero de 2022. Se incluyeron estudios publicados. en portugués, español, francés e inglés, sin límite de tiempo. Resultados: de los 954 documentos recuperados, se seleccionaron 13. En los estudios se utilizaron diferentes procedimientos de medición en relación con el equipo, el entorno y la preparación de los participantes. La edad media de la población femenina osciló entre 31 y 43 años. Los sitios de medición vulvar fueron los labios mayores y menores, el pliegue interlabial y el perineo. El valor de pH más bajo medido fue 4,6 y el más alto fue 6,3. Conclusiones: hubo una baja producción de estudios sobre pH vulvar y un énfasis de estudios en población de mujeres adultas. La diversidad de procedimientos y sitios de medición encontrados no permite realizar afirmaciones seguras sobre un rango de valores de pH en la superficie de la piel vulvar.

Índice de Dieta Mediterránea y pH Salival en Mujeres Adultas. Estudio Observacional / Mediterranean Diet Index and Salivary pH in Adult Women. Observational Study

El ser humano en el transcurso de la evolución ha cambiado la percepción de la alimentación dejando de lado el consumo de carne y sus derivados por factores éticos y morales, donde se sabe la dieta tiene gran relevancia en la salud general, siendo un factor de riesgo para la aparición de diversas enfermedades motivo por cual la saliva se ha utilizado como instrumento de diagnóstico Describir y comparar el índice de Dieta mediterránea según pH salival en mujeres estudiantes de Odontología de entre 20 a 30 años. Estudio descriptivo transversal comparativo. Participaron 17 mujeres adultas seleccionadas por criterio no probabilístico en la carrera de Odontología, quienes fueron evaluadas en su índice de Dieta mediterránea y pH salival. Se aplicó la prueba T de Student para muestras independientes y U Mann-Whitney para comparar características entre grupos en función del pH salival. Existen diferencias significativas entre grupos para la frecuencia de consumo de cereales integrales (p = 0,026), carnes magras (p = 0,021) y pH salival (p < 0,001). Existe un predominio hacia la baja adherencia a una dieta mediterránea, existiendo diferencias significativas en la frecuencia de consumo de cereales integrales y carnes magras, siendo el consumo de estos un indicador del riesgo de la cavidad oral determinado por pH.

The human being in the course of evolution has changed the perception of food, leaving aside the consumption of meat and its derivatives due to ethical and moral factors, where it is known that diet has great relevance in general health, being a factor of risk for the appearance of various diseases, which is why saliva has been used as a diagnostic tool. To describe and compare the Mediterranean Diet index according to salivary pH in female dentistry students between 20 and 30 years old. Comparative cross-sectional descriptive study. Seventeen adult women selected by non-probabilistic criteria participated in the Dentistry career, who were evaluated in their Mediterranean Diet index and salivary pH. Student's T test for independent samples and Mann-Whitney U test were applied to compare characteristics between groups based on salivary pH. There are significant differences between groups for the frequency of consumption of whole grains (p = 0.026), lean meats (p = 0.021) and salivary pH (p < 0.001). There is a predominance towards low adherence to a Mediterranean diet, with significant differences in the frequency of consumption of whole grains and lean meats, the consumption of these being an indicator of oral risk determined by pH.

Development and verification of a sulfosalicylic acid spectrophotometric method for determination of iron ion in medium for producing diphtheria toxin / 中国生物制品学杂志

@#Objective To develop and verify a sulfosalicylic acid spectrophotometric method for the determination of trace iron ions in diphtheria toxin medium,and apply it preliminarily.Methods The maximum absorbance of the complex of iron and sulfosalicylic acid was scanned by full spectrum;A method for the determination of iron ion in culture medium was developed by linear regression between the absorbance of the complex and the content of iron ion,and the stability,accuracy and precision of the method were verified.The effects of Ca~(2+),Mg~(2+),K~+,Na~+ and reactants on the method were investigated.Spectrophotometric method with sulfosalicylic acid was used to determine trace iron in the self-made and commercial medium for diphtheria toxin production.Sulfosalicylic acid spectrophotometry,ferrizine colorimetry and o-phenanthroline spectrophotometry were used to detect iron content in two kinds of culture media(beef trypsin digestion liquid and 5% polypeptone),and the detection results of the three methods were compared.Results The complex of iron and sulfosalicylic acid showed the maximum absorbance at the wavelength of 425 nm;There was a good linear relationship between the absorbance and concentration of iron ion in the range of 1～0.05 μg/mL,the detection limit was 0.05 μg/mL,and the standard equation was:Y=0.027 9 X+0.046 1,R~2> 0.99;The coefficients of variation(CVs) of A_(425) value of each concentration of standards measured every 5 min were less than 5%;Low(0.05 μg/mL),medium(0.5 μg/mL)and high concentration(1 μg/mL) of Fe~(3+) standard solutions were continuously determined for 3 times.The CVs of 9groups of each concentration measured in parallel were all less than 5% and the recovery rates were higher than 95%;Ca~(2+),Mg~(2+),K~+,Na~+,15 μL of sulfo salicylic acid(20%) and 50 μL of ammonia hydroxide(1:1) showed no interference in the method;The results of toxin-producing medium were consistent with those of diphtheria bacteria;The results of the three detection methods were consistent.Conclusion The developed spectrophotometric method with sulfo salicylic acid can determine the content of trace iron ions in diphtheria toxin medium accurately and effectively.

Effect of Biling Qutong Prescription on NLRP3， P2X7R， FN， and Hepatic Steatosis in Type 2 Diabetes Mellitus Complicated with Gouty Arthritis / 中国实验方剂学杂志

ObjectiveTo investigate the effects of Biling Qutong prescription （BLQT） on serum levels of NOD-like receptor thermal protein domain associated protein 3 （NLRP3）， purinergic ligand-gated ion channel 7 receptor （P2X7R）， fibronectin （FN）， and hepatic steatosis in patients with type 2 diabetes mellitus （T2DM） complicated with gouty arthritis （GA）. MethodSixty-four patients diagnosed with T2DM comorbid with GA and treated at the First Affiliated Hospital of Anhui University of Chinese Medicine from January 2019 to December 2022 were enrolled and randomly divided into a BLQT group （Chinese medicine group， 32 cases） and the ibuprofen group （western medicine group， 32 cases）. Thirty healthy individuals who underwent routine health examinations during the same period were assigned to the control group. The BLQT group and the western medicine group received basic treatment along with BLQT and ibuprofen， respectively. After 8 weeks of continuous treatment， the traditional Chinese medicine syndrome score （TCMSS） of the patients was evaluated before and after treatment. The differences in fasting plasma glucose （FPG）， 2-hour postprandial plasma glucose （2 h PG）， glycated hemoglobin （HbA1c）， fasting insulin （FINS）， homeostasis model assessment of insulin resistance （HOMA-IR）， serum uric acid （SUA）， serum creatinine （SCr）， total cholesterol （TC）， triglyceride （TG）， high-density lipoprotein cholesterol （HDL-C）， low-density lipoprotein cholesterol （LDL-C）， alanine aminotransferase （ALT）， aspartate aminotransferase （AST）， controlled attenuation parameter （CAP）， liver stiffness measurement （LSM）， NLRP3， P2X7R， and FN levels before and after treatment were compared. Adverse drug reactions that occurred during treatment were recorded. ResultThe TCMSS for joint redness， swelling， pain， joint burning， yellow urine， and red tongue with yellow and greasy coating， as well as total score were significantly reduced in both the BLQT group and the western medicine group as compared with those before treatment （P<0.05， P<0.01）. The BLQT group also showed a significant reduction in symptom scores such as dry mouth， polyuria， polydipsia， and slippery and rapid pulse （P<0.01）. Compared with the western medicine group after treatment， the BLQT group exhibited a more significant reduction in all symptom scores and total score （P<0.05， P<0.01）. The BLQT group and the western medicine group showed a decrease in FPG， 2 h PG， HbA1c， SCr， SUA， TG， TC， and LDL-C levels （P<0.05， P<0.01） after treatment， and the BLQT group showed decreased HOMA-IR， ALT， AST， and HDL-C levels （P<0.05， P<0.01） compared with those before treatment. When compared with the western medicine group after treatment， the BLQT group showed a more significant reduction in all laboratory parameters except for HDL-C （P<0.05， P<0.01）. Before treatment， NLRP3， P2X7R， and FN levels in both the BLQT group and the western medicine group were higher than those in the control group （P<0.01）. After treatment， NLRP3 and P2X7R levels in both groups significantly decreased （P<0.01）， and FN levels in the BLQT group also decreased significantly （P<0.01）. When compared with the western medicine group after treatment， the BLQT group showed a more significant reduction in NLRP3， P2X7R， and FN levels （P<0.01）. Before treatment， CAP and LSM levels in both the BLQT group and the western medicine group were higher than those in the control group （P<0.01）. After treatment， CAP and LSM levels in both groups decreased （P<0.05， P<0.01）. Compared with the western medicine group after treatment， the BLQT group showed a more significant reduction in CAP and LSM （P<0.01）. The incidence of adverse reactions was 3.13% （1/32） in the BLQT group and 15.63% （5/32） in the western medicine group， with no significant difference. ConclusionBLQT has good efficacy in patients with T2DM complicated with GA， which can significantly alleviate joint redness， swelling， heat， pain， limited mobility， dry mouth， and polydipsia， reduce blood glucose， uric acid， and lipid levels， suppress the high expression of NLRP3， P2X7R， and FN， and improve hepatic steatosis.

Leptospiral c-di-AMP-binding protein regulates potassium ion transport / 中华微生物学和免疫学杂志

Objective:To investigate whether KtrA was a binding protein of c-di-AMP, the second messenger in Leptospira, and to explore the function and regulatory mechanism of the c-di-AMP-KtrA/B system. Methods:KtrA gene was amplified by PCR and cloned into pET42a plasmid to construct the pET42a ktrA prokaryotic expression vector. Then the vector was transferred into E. coli BL21DE3 to construct an engineering bacterium E. coli BL21DE3 pET42a-ktrA for the expression of recombinant KtrA (rKtrA). The expressed rKtrA was purified by affinity chromatography. BIAcore technology was used to detect the binding ability of rKtrA to c-di-AMP. Bacterial two-hybrid analysis was used to analyze the interaction between KtrA and KtrB in the leptospiral Ktr system with or without exogenetic c-di-AMP. The above genes were then complemented into the potassium transport-deficient E. coli mutants to analyze the function of the c-di-AMP-KtrA/B pathway. Results:An prokaryotic engineering bacterium for the expression of ktrA gene of Leptospira was constructed successfully. The purified rKtrA could specifically bind to c-di-AMP. There was interaction between KtrA and KtrB, but the interaction could be dissociated by c-di-AMP. The KtrA/B system was involved in potassium ion uptake and it was negatively regulated by c-di-AMP. Conclusions:Leptospiral KtrA was a c-di-AMP-binding protein and the c-di-AMP-KtrA/B system was involved in potassium ion transport.

Difference analysis of 18F-FMISO PET/CT hypoxia imaging in response to heavy ion radiotherapy in patients with non-small cell lung cancer / 中华核医学与分子影像杂志

Objective:To explore the clinical value of 18F-fluoromisonidazole (FMISO) PET/CT hypoxia imaging in early response to heavy ion radiotherapy in patients with non-small cell lung cancer(NSCLC). Methods:From April 2018 to January 2021, the 18F-FMISO PET/CT images of 23 NSCLC patients (19 males, 4 females; age (64.9±10.3) years) who received heavy ion radiotherapy in Shanghai Proton and Heavy Ion Center were retrospectively analyzed. The evaluation parameters included tumor volume (TV), tumor to background ratio (TBR) before and after radiotherapy. Patients were divided into hypoxia group and non-hypoxia group with the baseline TBR value≥1.4 as hypoxia threshold. Wilcoxon signed rank test was used to compare the differences of TV and TBR before and after radiotherapy in 2 groups. Results:Of 23 NSCLC patients, 17 were hypoxia and 6 were non-hypoxia. Compared with the baseline, TV after the radiotherapy (59.44(22.86, 99.43) and 33.78(8.68, 54.44) cm 3; z=-3.05, P=0.002) and TBR after the radiotherapy (2.25(2.09, 2.82) and 1.42(1.24, 1.67); z=-3.39, P=0.001) of the hypoxia group were significantly lower, while TV (16.19(6.74, 36.52) and 8.59(4.38, 25.47) cm 3; z=-1.57, P=0.120) and TBR (1.19(1.05, 1.27) and 1.10 (0.97, 1.14); z=-1.89, P=0.060) of the non-hypoxia group decreased with no significant differences. Conclusions:Hypoxic NSCLC tumors are sensitive to heavy ion radiation. Compared with non-hypoxic tumors, hypoxic tumors respond more quickly, and a significant reduction in TV can be observed early after radiotherapy. Heavy ion radiation can significantly improve tumor hypoxia.

A study on the conversion of prescribed dose for radiotherapy of logistic nanodosimetry model and microdosimetric kinetic model based on gamma analysis / 中华放射肿瘤学杂志

Objective:To validate the feasibility of the gamma analysis method in the study of prescription dose conversion between logistic nanodosimetry model (LNDM) and microdosimetric kinetic model (MKM) basing on the Chinese self-developed model LNDM by applying clinical experiences of National Institute of Radiological Science (NIRS).Methods:Physical dose distributions derived from the MKM- and LNDM-based carbon ion treatment plans were compared via the method of gamma analysis under the open-source treatment planning platform matRad. In this way, the prescribed dose conversion factor between the MKM- and LNDM-based treatment plans was obtained. Using water phantoms, the influence of geometric shape, size, depth of target volume (TV), prescribed dose and field setting on the conversion factor was investigated comprehensively. Moreover, preliminary verification of the acquired conversion factor was conducted on the C-shape model and a case of liver cancer patient.Results:The conversion factor depended on the field setting rather than the TV shape. Under the condition of single field, the conversion factor was positively correlated with the size and depth of TV, and the prescribed dose. Moreover, the conversion factor was successfully verified using the C-shape model and the patient with liver cancer, where the gamma passing rates (2%/2 mm) of the physical dose distribution generated by the MKM and LNDM treatment plans were 92.79% and 91.19%, respectively.Conclusions:The conversion factors (f=D LNDM/D MKM) obtained in this study might provide guidance for the prescribed dose setting during the carbon ion treatment planning based on the LNDM. Besides, the gamma analysis method could be used for the study of the prescribed dose conversion between different models.

Clinical report of two dose fractionation modes using carbon ion beam therapy in the lymph node drainage area for lung cancer / 中华放射肿瘤学杂志

Objective:To compare the adverse reactions, efficacy and survival rate of carbon ion beam irradiation in the elective lymph node (ENI) drainage area of locally advanced non-small cell lung cancer (LA-NSCLC) with relative biological effect (RBE) dose of 48 Gy using 16 and 12 fractions.Methods:A total of 72 patients with pathologically confirmed LA-NSCLC admitted to Wuwei Heavy Ion Center of Gansu Wuwei Tumor Hospital from June 2020 to December 2021 were enrolled and simple randomly divided into groups A and B, with 36 patients in each group. Patients in groups A and B were treated with carbon ion beam irradiation to the lymph node drainage area with 48 Gy (RBE) using 16 and 12 fractions. The acute and chronic adverse reactions, efficacy and survival rate were observed. The survival curve was drawn by Kaplan-Meier method. Difference test was conducted by log-rank test.Results:The median follow-up time was 13.9 (8.8-15.7) months in group A and 14.6 (6.3-15.9) months in group B. Sixteen (44.4%) patients were effectively treated in group A and 9 (25%) patients in group B. Thirty-four (94.4%) cases achieved disease control in group A and 30 (83.3%) cases in group B. Statistical analysis showed that the overall survival rate in group B was similar to that in group A ( χ2=1.192, P=0.275). Comparison of planning parameters between two groups showed CTV volume, D mean, V 5 Gy(RBE), V 20 Gy(RBE) and V 30 Gy(RBE) of the affected lung, cardiac V 20 Gy(RBE), V 30 Gy(RBE) and D mean, esophageal V 30 Gy(RBE), V 50 Gy(RBE), D max and D mean, D max of the trachea and spinal cord had no significant difference (all P>0.05). No grade 3 or 4 adverse reactions occurred in the enrolled patients during treatment and follow-up. No statistical differences were observed in the acute radiation skin reaction ( χ2=5.134, P=0.077), radiation esophagitis ( χ2=1.984, P=0.371), and advanced radiation pneumonia ( χ2=6.185, P=0.103) between two groups. Conclusions:The two dose fractionation modes of carbon ion therapy system are equally safe in the mediastinal lymphatic drainage area of LA-NSCLC, and the adverse reactions are controllable. The long-term efficacy still needs further observation.

Role of P2X7/NLRP3 inflammasome pathway in cognitive impairment in sleep deprived mice / 中华行为医学与脑科学杂志

Objective:To investigate the possible role and mechanism of purinergic ligand-gated ion channel 7(P2X7)/nucleotide-binding oligomerization domain-like receptor protein 3(NLRP3) inflammasome pathway in cognitive impairment induced by sleep deprivation (SD)mice.Methods:SPF grade male C57BL / 6J mice aged 6-8 weeks were randomly divided into 3 groups according to the random number table method with 6 mice in each group.They were normal control group (CC group), SD group and SD+ P2X7 receptor antagonist brilliant blue G(BBG) group (SD+ BBG group). Modified multiple platform method was used to establish a 5-day SD model in mice.During the SD intervention period, the mice in SD+ BBG group were injected with BBG(50 mg/kg) intraperitoneally once a day, while the mice in CC group and SD group were injected with the same volume of 0.9% sodium chloride solution.Morris water maze was conducted to evaluate the cognitive function of mice.The protein expression levels of P2X7, NLRP3, caspase-1, apoptosis-associated proteins(ASC) and interleukin-1β(IL-1β) in hippocampus were detected by Western blot.RT-qPCR was used to detect the mRNA expression levels of tumor necrosis factor-α(TNF-α), IL-1β, interleukin-18(IL-18) and microglial polarization surface markers CD206 and CD86 in hippocampus.Graph pad Prism 8.0 software and SPSS 25.0 software were used for statistical analysis and mapping.Results:(1) The interaction effect between time and groups of escape latency in three groups of mice was significant ( F=15.76, P<0.001). From the 2nd to 5th day, the escape latencies of mice in SD group were higher than those of CC group, while the escape latencies of mice in SD+ BBG group were lower than those of SD group (all P<0.05). (2)The results of the space exploration experiment showed that there were statistically significant differences in target quadrant residence time and the times of crossing the platform( F=6.65, P=0.009; F=12.39, P<0.001). The target quadrant residence time ((23.42±0.55) s) and times of crossing the platform ((17.67±0.71) times) of the SD group were both lower than those of the CC group ((29.48±1.78) s, (23.33±0.95) times) (both P<0.05), while the target quadrant residence time ((28.62±1.19) s) and the times of crossing the platforms ((21.33±0.76) times) of the SD+ BBG group were both higher than those of the SD group (both P<0.05). (3)There were statistically significant differences in the protein levels of inflammatory related proteins such as P2X7, NLRP3, caspase-1, ASC and IL-1β in the hippocampus of mice among the 3 groups( F=8.23, 8.97, 8.45, 54.42, 8.12, all P<0.05). Compared with CC group, the protein levels of P2X7 ((0.93±0.02), (0.71±0.04)), NLRP3 ((0.97±0.04), (0.62±0.09)), caspase-1 ((1.00±0.03), (0.76±0.07)), ASC ((0.96±0.02), (0.77±0.04)) and IL-1β ((0.85±0.07), (0.54±0.04)) in SD group were all higher (all P<0.05). Compared with SD group, the protein levels of P2X7 (0.74±0.05), NLRP3 (0.78±0.02), caspase-1 (0.74±0.04), ASC (0.67±0.02), IL-1β (0.53±0.07) in SD+ BBG group were all lower (all P<0.05). (4)There were statistically significant differences in the mRNA levels of IL-18, IL-1β, TNF-α, CD86 and CD206 in hippocampus among the three groups ( F=12.80, 12.28, 105.80, 7.06, 30.19, all P<0.05). The mRNA levels of IL-18, IL-1β, TNF-α, CD86 in SD group were all higher than those in CC group(all P<0.05), while the mRNA level of CD206 in SD group was lower than that in CC group( P<0.05). Compared with SD group, the mRNA levels of IL-18, IL-1β, TNF-α, CD86 were lower in SD+ BBG group (all P<0.05), while the CD206 mRNA level of SD+ BBG group was higher than that in SD group( P<0.05). Conclusion:SD intervention can lead to cognitive impairment and increased expression of P2X7 in hippocampus of mice, which may be related to the activation of P2X7/ NLRP3 inflammasome signaling pathway, promoting the polarization of microglia into pro-inflammatory type and up-regulating the expression of pro-inflammatory cytokines.Inhibition of P2X7 can improve the cognitive function of mice.

Establishment of mouse pancreatic ductal organoids and exploration of its physiological functions / 中华胰腺病杂志

Objective:To establish culture system for mouse pancreatic ductal organoids and investigate the morphology and physiological functions of the organoids.Methods:Pancreatic tissues were taken from C57BL/6 mice (6-8 weeks) and digested by collagenase Ⅳ. The pancreatic ducts were separated and collected and then the pancreatic organoids were cultured in the complete medium after Matrix gel embedding. Morphological evaluation of the organoids was performed after hematoxylin-eosin staining. The expression and localization of markers for organoids were identified by Western Blot and immunofluorescence staining; and the expression and localization of ion channels and antimicrobial peptides of the organoids were detected by agarose gel electrophoresis and immunofluorescence staining.Results:Mouse pancreatic organoids were successfully established, which could be stably passaged for 10 generations. The organoids grew spherically and formed a duct-like structure. The internal cavity corresponded to the lumen of pancreatic duct tissue. The pancreatic organoids stably expressed stem progenitor cell marker gene SOX9 and ductal epithelial cell-specific gene KRT19, which were both localized in the epithelium. The organoids did not express amylase. The organoids maintained stable expression of epithelial ion channels Clcn1, Kcnma1, CFTR, Slc12a5, Slc26a3, Slc26a6 and Scnn1a, low expression of Ano1 and no expression of Clcn3, Kcna1, Kcna2, Kcnd3, Kcnh1, Atp12a, Slc4a4, Slc9a1, Slc12a2 and Slc26a11; and CFTR highly expressed in epithelial cells. The organoids maintained high expression of antimicrobial peptides Reg3a, CRAMP and glycoprotein 2, low expression of Defb1, Defb2, and Defb3 and no expression of Defa1 and Defa4; and both CRAMP and Reg3a were expressed in the epithelial cells and secreted into the lumen of the organoids.Conclusions:Mouse pancreatic organoids are successfully established, which can be stably passaged. The organoids maintain the characteristics of ductal epithelial cells and can be used as an in vitro model to study the physiology of pancreatic ducts.

Identification,structure elucidation and origin of a common pyridinium-thiocyanate intermediate in electrospray mass spectrometry among the benziamidazole-class proton pump inhibitors / 药物分析学报

During the analysis of benziamidazole-class irreversible proton pump inhibitors,an unusual mass spectral response with the mass-to-charge ratio at[M+10]+intrigued us,as it couldn't be assigned to any literature known relevant structure,intermediate or adduct ion.Moreover,this mysterious mass pattern of[M+10]+has been gradually observed by series of marketed proton pump inhibitors,viz.omeprazole,pantoprazole,lansoprazole and rabeprazole.All the previous attempts to isolate the corresponding component were unsuccessful.The investigation of present work addresses this kind of signal to a pyridinium thiocyanate mass spectral intermediate(10),which is the common fragment ion of series of labile aggregates.The origin of such aggregates can be traced to the reactive intermediates formed by acid-promoted degradation.These reactive intermediates tend to react with each other and give raise series of complicated aggregates systematically in a water/acetonitrile solution by electrospray ioniza-tion.The structure of the corresponding pyridinium thiocyanate species of omeprazole(10a)has been eventually characterized with the help of synthetic specimen(10a').Our structural proposal as well as its origin was supported by in situ nuclear magnetic resonance,chemical derivatization and colorimetric experiments.

Breath-by-breath measurement of exhaled ammonia by acetone-modifier positive photoionization ion mobility spectrometry via online dilution and purging sampling / 药物分析学报

Exhaled ammonia(NH3)is an essential noninvasive biomarker for disease diagnosis.In this study,an acetone-modifier positive photoionization ion mobility spectrometry(AM-PIMS)method was developed for accurate qualitative and quantitative analysis of exhaled NH3 with high selectivity and sensitivity.Acetone was introduced into the drift tube along with the drift gas as a modifier,and the characteristic NH3 product ion peak of(C3H6O)4NH4+(K0=1.45 cm2/V·s)was obtained through the ion-molecule reaction with acetone reactant ions(C3H6O)2H+(K0=1.87 cm2/V·s),which significantly increased the peak-to-peak resolution and improved the accuracy of exhaled NH3 qualitative identification.Moreover,the interference of high humidity and the memory effect of NH3 molecules were significantly reduced via online dilution and purging sampling,thus realizing breath-by-breath measurement.As a result,a wide quantitative range of 5.87-140.92 μmol/L with a response time of 40 ms was achieved,and the exhaled NH3 profile could be synchronized with the concentration curve of exhaled CO2.Finally,the analytical capacity of AM-PIMS was demonstrated by measuring the exhaled NH3 of healthy subjects,demon-strating its great potential for clinical disease diagnosis.

Drug adulteration analysis based on complexation with cyclodextrin and metal ions using ion mobility spectrometry / 药物分析学报

Drug adulteration and contamination are serious threats to human health therefore,their accurate monitoring is very important.Allopurinol(Alp)and theophylline(Thp)are commonly used drugs for the treatment of gout and bronchitis,while their isomers hypoxanthine(Hyt)and theobromine(Thm)have no effect and affect the efficacy of the drug.In this work,the drug isomers of Alp/Hyt and Thp/Thm are simply mixed with α-,β-,y-cyclodextrin(CD)and metal ions and separated using trapped ion mobility spectrometry-mass spectrometry(TIMS-MS).TIMS-MS results showed that Alp/Hyt and Thp/Thm iso-mers could interact with CD and metal ions and form corresponding binary or ternary complexes to achieve their TIMS separation.Different metal ions and CDs showed different separation effect for the isomers,among which Alp and Hyt could be successfully distinguished from the complexes of[Alp/Hyt+y-CD+Cu-H]+with separation resolution(Rp-p)of 1.51;whereas Thp and Thm could be baseline separated by[Thp/Thm+y-CD+Ca-H]+with Rp-p of 1.96.Besides,chemical calculations revealed that the complexes were in the inclusion forms,and microscopic interactions were somewhat different,making their mobility separation.Moreover,relative and absolute quantification was investigated with an internal standard to determine the precise isomers content,and good linearity(R2＞0.99)was ob-tained.Finally,the method was applied for the adulteration detection where different drugs and urine were analyzed.In addition,due to the advantages of fast speed,simple operation,high sensitivity,and no chromatographic separation required,the proposed method provides an effective strategy for the drug adulteration detection of isomers.

Prognosis assessment of strong ion gap in adult patients with cardiac arrest / 中华急诊医学杂志

Objective:To investigate the correlation between strong ion gap (SIG) and prognosis of adult hospitalized patients who experienced cardiac arrest (CA).Methods:A retrospective cohort study was conducted on adult CA patients (≥18 years old) who were admitted to the intensive care unit (ICU) for the first time from the Medical Information Mart for Intensive Care Ⅲ (MIMIC-Ⅲ) database from 2001 to 2012. The patients were divided into 3 groups based on the tertiles of serum SIG value. The clinical baseline characteristics and related data of CA patients were compared. Kaplan-Meier method was used to draw the 28- and 90-day cumulative survival curves of CA patients. Meanwhile, the log-rank test was used to compare the differences in the survival curves among different groups, and Cox proportional hazard regression model was established to analyze whether SIG was an independent predictor of all-cause mortality in CA patients.Results:Six hundred and six adult CA patients were eligible for final analysis. The patients were divided into 3 groups based on the tertiles of serum SIG value [<3.91 mmol/L ( n=202), 3.91~7.32 mmol/L ( n=202) and >7.32 mmol/L ( n=202)]. The mean age was (66.91±15.95) years and 382 patients (63.04%) were male. The all-cause mortality rates of ICU, 28 days and 90 days were 36.47%, 49.17% and 56.93%, respectively. There were significant differences in SOFA score, SIG, anion gap, pH, lactic acid, white blood cells, prothrombin time, creatinine, blood potassium, blood phosphorus, hypertension, coronary heart disease, cardiogenic shock, and ICU, 28-day and 90-day all-cause mortality among the 3 groups (all P<0.05). The Kaplan-Meier survival curves showed that the 28- and 90-day cumulative survival rates of CA patients decreased gradually with the increase of SIG level, and the differences were statistically significant among the 3 groups (all P<0.001). Multivariate Cox proportional hazard models showed that the increase of SIG level (>7.32 mmol/L) was an independent risk factor for 28-day ( HR=1.610, 95% CI: 1.177-2.203, P=0.003) and 90-day all-cause mortality ( HR=1.506, 95% CI: 1.123-2.019, P=0.006) among CA patients, after adjusting for the related confounders. Conclusions:The elevated SIG level (>7.32 mmol/L) is an independent predictor of 28- and 90-day all-cause mortality in CA patients. The calculation of SIG level in these patients is helpful for early identification of patients with poor prognosis.

Progress on the impact of pathogenic gene mutations in epilepsy on treatment choices / 国际儿科学杂志

In the past decade, significant progress has been made in the study of epilepsy-causing genetic mutations and the molecular mechanisms of epilepsy clinical manifestations.A growing number of studies have shown that the mechanism of action of pathogenic genes related to clinical symptoms shows significant correlation.In the selection of antiepileptic drugs for patients with different gene mutation, early identification of pathogenic genes has guiding significance for the selection of antiepileptic drugs.This review summairzes common epilepsy pathogenic genes, including ion channels genes, cellular metabolism related genes and cell signaling pathway related genes, and research progress on therapeutic targets corresponding to pathogenic genes in recent years.As research deepens, specific gene defects and their machanisms of action provide a basis for studying new treatment methods.

Quantification of complete viral particles in inactivated avian influenza virus antigen by high performance size exclusion chromatography coupled with multi-angle laser light scattering / 生物工程学报

We developed a method for accurate quantification of the intact virus particles in inactivated avian influenza virus feedstocks. To address the problem of impurities interference in the detection of inactivated avian influenza virus feedstocks by direct high performance size exclusion chromatography (HPSEC), we firstly investigated polyethylene glycol (PEG) precipitation and ion exchange chromatography (IEC) for H5N8 antigen purification. Under the optimized conditions, the removal rate of impurity was 86.87% in IEC using DEAE FF, and the viral hemagglutination recovery was 100%. HPSEC was used to analyze the pretreated samples. The peak of 8.5-10.0 min, which was the characteristic adsorption of intact virus, was analyzed by SDS-PAGE and dynamic light scattering. It was almost free of impurities and the particle size was uniform with an average particle size of 127.7 nm. After adding antibody to the IEC pretreated samples for HPSEC detection, the characteristic peak disappeared, indicating that IEC pretreatment effectively removed the impurities. By coupling HPSEC with multi-angle laser scattering technique (MALLS), the amount of intact virus particles in the sample could be accurately quantified with a good linear relationship between the number of virus particles and the chromatographic peak area (R2=0.997). The established IEC pretreatment-HPSEC-MALLS assay was applied to accurate detection of the number of intact virus particles in viral feedstocks of different subtypes (H7N9), different batches and different concentrations, all with good applicability and reproducibility, Relative standard deviation < 5%, n=3.

Advances of ultrasonic neuromodulation based on mechanosensitive channels / 生物工程学报

Mechanosensitive channels (MSCs) are special membrane proteins that can convert mechanical stimulation into electrical or chemical signals. These channels have become potential targets for ultrasonic neuromodulation due to their properties. The good spatial resolution and focusing effect of ultrasound make it theoretically possible to achieve non-invasive whole-brain localization. Therefore, ultrasonic neuromodulation is a promising method for performing physical neuromodulation and treating neurological disorders. To date, only a few ion channels have been reported to be activated by ultrasound, while recent research has identified more channels with mechanosensitive properties. Moreover, the opening process and mechanism of MSCs under ultrasound excitation remain unknown. This review provides an overview on recent research advances and applications in MSCs, including large conductance mechanosensitive channels, transient receptor potential channels, degenerated protein/epithelial sodium channels, two-pore potassium channels, and piezo channels. These findings will facilitate future studies and applications of ultrasonic neuromodulation.