Objective To explore the effect of Sangxing Zhike Formula in rats with cough vari-ant asthma(CVA)and its possible mechanism based on the cyclic adenosine monophosphate(cAMP)/cystic fibrosis transmembrane conductance regulator(CFTR)pathway.Methods SD rats were randomly divided into control group,model group,dexamethasone group(0.5 mg/kg)and low-,medium-,high-dose Sangxing Zhike Formula groups(9.6,19.2 and 38.4 g/kg)using a ran-dom number table method,with 9 rats in each group.Except for the control group,CVA rat models were established in the other groups.Rats in each group were administered the drug by gavage once a day for 14 consecutive days.The general conditions of rats in each group were observed.Enzyme-linked immunosorbent assay(ELISA)was used to detect the levels of interleukin-1β(IL-1β)and interleukin-18(IL-18)in rat serum.Hematoxylin-eosin(HE)staining and periodic acid-Schiff(PAS)staining were used to observe the pathological changes in rat lung and bronchial tissues,and the acid-base balance of airway surface liquid(ASL)was measured.Western blot and real-time fluorescence quantitative polymerase chain reaction(RT-qPCR)were used to detect the expression levels of pro-tein kinase A(PKA),CFTR protein and their mRNA in lung tissues of rats.Results Compared with the control group,rats in the model group showed listlessness,dull fur,slow weight gain,a significantly expanded area of alveolar septal consolidation,and a large number of inflammatory cell infiltrations around the bronchi.Compared with the model group,rats in each intervention group had better general conditions and reduced inflammatory infiltrations in lung tissues and bronchial lu-mens.Compared with the control group,the serum levels of IL-1 β and IL-18 in the model group were increased,and the pH values of ASL in the model group,low-dose Sangxing Zhike Formula group,medium-dose Sangxing Zhike Formula group,and high-dose Sangxing Zhike Formula group were all decreased,with statistically significant differences(P＜0.05).Compared with the model group,the serum levels of IL-1β and IL-18 in each intervention group were decreased,and the pH values of ASL in the dexamethasone group,medium-dose Sangxing Zhike Formula group,and high-dose Sangxing Zhike Formula group were increased,with statistically significant differences(P＜0.05).Compared with the control group,the expressions of PKA protein and PKA mRNA in the model group,low-dose Sangxing Zhike Formula group,and medium-dose Sangxing Zhike Formula group were all decreased,and the expressions of CFTR protein and CFTR mRNA in the model group and each intervention group were all decreased,with statistically significant differences(P＜0.05).Compared with the model group,the expressions of PKA protein and PKA mRNA in the dexametha-sone group and high-dose Sangxing Zhike Formula group were increased,and the expressions of CFTR protein and CFTR mRNA in the high-dose Sangxing Zhike Formula group were increased,with statistically significant differences(P＜0.05).Conclusion Sangxing Zhike Formula can im-prove the general conditions of CVA rats,regulate the acid-base balance of ASL,reduce airway in-flammatory cell infiltration andairway remodeling,and decrease the levels of inflammatory factors IL-1β and IL-18.Its mechanism may be related to the cAMP/CFTR pathway.

Objective:To explore the clinical characteristics and sputum antibacterial protein levels of patients with cough-variant asthma (CVA) due to deficiency of different Zang-Fu organs.Methods:A total of 109 patients with CVA admitted to the Department of Respiratory, Affiliated Hospital of Traditional Chinese Medicine, Xinjiang Medical University from January 2023 to June 2024 were selected. According to the deficiency and damage of the internal organs of the patients, they were divided into 45 cases in the lung qi deficiency group, 39 cases in the lung and spleen deficiency group, and 25 cases in the lung and kidney deficiency group. Thirty healthy individuals were taken as the normal control group. The general information of the subjects was collected. The disease course of CVA patients, the number of acute exacerbations and hospitalizations, the Asthma Control Test (ACT) score, the Traditional Chinese Medicine (TCM) syndrome score, and the results of pulmonary function tests [forced vital capacity (FVC), forced expiratory volume in one second (FEV 1), FEV 1/FVC, early peak expiratory flow rate (MEF 25), mid-peak expiratory flow rate (MEF 50), late peak expiratory flow rate (MEF 75)], and the levels of antibacterial proteins [β -defensin (β-DF), antimicrobial peptide LL-37, lysozyme (LZM), lactoferrin (LTF)] in the sputum of the subjects were detected by enzyme-linked immunosorbent assay. Results:There were no statistically significant differences in the disease course, the number of acute exacerbations and the number of hospitalizations among the three groups of CVA patients (all P>0.05). There were statistically significant differences in the ACT scores and TCM syndrome scores among the three groups of CVA patients ( F=82.221, 194.577, all P<0.05). Among them, the ACT score was in the order of lung Qi deficiency group>lung and spleen deficiency group>lung and kidney deficiency group, and the TCM syndrome score was in the order of lung qi deficiency group0.05), while there was a statistically significant difference in MEF 25 ( Z=53.896, P<0.05). Among them, the MEF 25 in the lung and kidney deficiency group was significantly lower than that in the lung qi deficiency group and the lung and spleen deficiency group (all P<0.05). The contents of β-DF, antimicrobial peptide LL-37, LZM and LTF in the sputum of the three groups of CVA patients were all higher than those in the normal control group (all P<0.05). Among them, the content of LZM in sputum of the lung and kidney deficiency group was higher than that of the lung and spleen deficiency group, and the content of antimicrobial peptide LL-37 was lower than that of the lung and spleen deficiency group. The differences were statistically significant (all P<0.05). Conclusions:The clinical characteristics of patients with CVA due to deficiency of different Zang-Fu organs are different, providing a theoretical basis for the syndrome differentiation and treatment of CVA by Zang-Fu organs. The level of antibacterial protein in sputum of the CVA group was higher than that of the normal control group. This might be because the onset of CVA is often induced by infection.

Objective:To explore the clinical characteristics and sputum antibacterial protein levels of patients with cough-variant asthma (CVA) due to deficiency of different Zang-Fu organs.Methods:A total of 109 patients with CVA admitted to the Department of Respiratory, Affiliated Hospital of Traditional Chinese Medicine, Xinjiang Medical University from January 2023 to June 2024 were selected. According to the deficiency and damage of the internal organs of the patients, they were divided into 45 cases in the lung qi deficiency group, 39 cases in the lung and spleen deficiency group, and 25 cases in the lung and kidney deficiency group. Thirty healthy individuals were taken as the normal control group. The general information of the subjects was collected. The disease course of CVA patients, the number of acute exacerbations and hospitalizations, the Asthma Control Test (ACT) score, the Traditional Chinese Medicine (TCM) syndrome score, and the results of pulmonary function tests [forced vital capacity (FVC), forced expiratory volume in one second (FEV 1), FEV 1/FVC, early peak expiratory flow rate (MEF 25), mid-peak expiratory flow rate (MEF 50), late peak expiratory flow rate (MEF 75)], and the levels of antibacterial proteins [β -defensin (β-DF), antimicrobial peptide LL-37, lysozyme (LZM), lactoferrin (LTF)] in the sputum of the subjects were detected by enzyme-linked immunosorbent assay. Results:There were no statistically significant differences in the disease course, the number of acute exacerbations and the number of hospitalizations among the three groups of CVA patients (all P>0.05). There were statistically significant differences in the ACT scores and TCM syndrome scores among the three groups of CVA patients ( F=82.221, 194.577, all P<0.05). Among them, the ACT score was in the order of lung Qi deficiency group>lung and spleen deficiency group>lung and kidney deficiency group, and the TCM syndrome score was in the order of lung qi deficiency group0.05), while there was a statistically significant difference in MEF 25 ( Z=53.896, P<0.05). Among them, the MEF 25 in the lung and kidney deficiency group was significantly lower than that in the lung qi deficiency group and the lung and spleen deficiency group (all P<0.05). The contents of β-DF, antimicrobial peptide LL-37, LZM and LTF in the sputum of the three groups of CVA patients were all higher than those in the normal control group (all P<0.05). Among them, the content of LZM in sputum of the lung and kidney deficiency group was higher than that of the lung and spleen deficiency group, and the content of antimicrobial peptide LL-37 was lower than that of the lung and spleen deficiency group. The differences were statistically significant (all P<0.05). Conclusions:The clinical characteristics of patients with CVA due to deficiency of different Zang-Fu organs are different, providing a theoretical basis for the syndrome differentiation and treatment of CVA by Zang-Fu organs. The level of antibacterial protein in sputum of the CVA group was higher than that of the normal control group. This might be because the onset of CVA is often induced by infection.

Objective To explore the trends and patterns of changes in airway inflammation,mitochondrial function,and arginine levels in patients with different degrees of asthma.Methods A total of 122 patients with acute asthma admitted to the Affiliated Traditional Chinese Medicine Hospital of Xinjiang Medical University from November 2016 to May 2017 were selected as the research subjects.According to the severity grading criteria,the patients were divided into the intermittent state group(n=45),mild asthma group(n=23),moderate asthma group(n=30),and severe asthma group(n=24).Another 44 healthy individuals who underwent physical examinations at the Medical Examination Center of the Affiliated Traditional Chinese Medicine Hospital of Xinjiang Medical University from November 2016 to May 2017 were selected as the healthy control group.About 18-20 mL of venous blood was extracted from each group of subjects.The levels of L-arginine(L-Arg)and asymmetric dimethylarginine(ADMA)were detected by high-performance liquid chromatography-tandem mass spectrometry,and the levels of type 1 protein arginine methyltransferase(PRMT1),dimethylarginine dimethylaminohydrolase 1(DDAH1),reactive oxygen species(ROS),thiobarbituric acid reactive substances(TBARS),8-isoprostaglandin(8-iso),lipid peroxide(LPO),and malondialdehyde(MDA)were detected by enzyme-linked immunosorbent assay.Platelets and mitochondria were extracted from each group of subjects.The platelet mitochondrial membrane potential(MMP)was measured using JC-1 flow cytometry,and the mitochondrial adenosine triphosphate(ATP)and cytochrome C oxidase(COX)activity were detected.Results The level of 8-iso in plasma of patients in the intermittent state group,mild asthma group,moderate asthma group,and severe asthma group were significantly higher than that in the healthy control group(P＜0.05);the level of 8-iso in plasma of patients in the severe asthma group was significantly higher than that in the intermittent state group,mild asthma group,and moderate asthma group(P＜0.05);the level of 8-iso in plasma of patients in the intermittent state group,mild asthma group,and moderate asthma group showed an increasing trend,but there was no statistically significant difference(P＞0.05).There was no statistically significant difference in the TBARS level in the plasma of subjects in the five groups(P＞0.05).The levels of ROS and MDA in plasma of patients in the intermittent state group,mild asthma group,moderate asthma group,and severe asthma group were significantly higher than those in the healthy control group(P＜0.05);the levels of ROS and MDA in plasma of patients in the moderate asthma group and severe asthma group were significantly higher than those in the intermittent state group and mild asthma group(P＜0.05);there was no statistically significant difference in plasma ROS and MDA levels between the intermittent state group and the mild asthma group(P＞0.05),and there was no statistically significant difference in plasma ROS and MDA levels between the moderate asthma group and the severe asthma group(P＞0.05).The plasma LPO level of patients in the intermittent state group,mild asthma group,moderate asthma group,and severe asthma group was significantly higher than that in the healthy control group(P＜0.05);the plasma LPO level of patients in the moderate asthma group and severe asthma group was significantly higher than that in the intermittent state group(P＜0.05);there was no statistically significant difference in plasma LPO level of patients in the mild asthma group,moderate asthma group,and severe asthma group(P＞0.05).The mitochondrial MMP,ATP,and COX activity in the intermittent state group,mild asthma group,moderate asthma group,and severe asthma group were significantly lower than those in the healthy control group(P＜0.05);there was no statistically significant difference in mitochondrial MMP,ATP,and COX activity of patients in the intermittent state group,mild asthma group,moderate asthma group,and severe asthma group(P＞0.05).The levels of plasma L-Arg,the ratio of L-Arg/ADMA,and DDAH1 in the intermittent state group,mild asthma group,moderate asthma group,and severe asthma group were significantly lower than those in the healthy control group(P＜0.05);there was no statistically significant difference in plasma L-Arg,the ratio of L-Arg/ADMA,and DDAH1 levels of patients in the intermittent state group,mild asthma group,moderate asthma group,and severe asthma group(P＞0.05).The plasma ADMA and PRMT1 levels showed no statistically significant difference among the five groups of patients(P＞0.05).Conclusion Asthma patients exhibit mitochondrial dysfunction and abnormal arginine metabolism at any stage of the disease.Although there is no statistically significant difference in the change trend at the cellular micro level among patients with different stages of asthma,the trend of changes in oxidative damage in the body is consistent with the aggravation of the disease.

Objective:To assess the efficiency of modified enrichment method for cell-free fetal DNA (cffDNA) through purified superparamagnetic beads during non-invasive prenatal testing (NIPT).Methods:A total of 26 252 pregnant women undergoing NIPT at the Maternal and Child Health Care Hospital of Haidian District from December 2017 to September 2022 were recruited and randomly assigned into the conventional group ( n = 10 573) and the modified enrichment group ( n = 15 679), who were then subjected to the screening and enrichment of the cffDNA using a conventional and modified technique, respectively. High-risk pregnant women detected by NIPT were subjected to invasive prenatal diagnosis. All women were followed up for their pregnancy outcomes, and the detection efficacy of the two methods was compared in terms of fragment size, concentration of cffDNA, duplicate detection rate, and indices of clinical laboratory tests. Results:The fragment size of the main peak of the cell-free DNA library of the modified enrichment group was significantly lower than that of the conventional group [267 (264, 269) bp vs. 294 (292, 296) bp, P<0.01], while the concentration of cffDNA was significantly higher [21.86% (17.61%, 26.36%) vs. 9.08% (6.87%, 11.87%), P<0.01]. In addition, the duplicate detection rate (0.740% vs. 2.02%, χ2=83.90, P<0.01) and detection failure rate (0.006% vs. 0.057%, P<0.05) in the modified enrichment group were significantly lower than those of the conventional group. The combined positive predictive value (PPV) in both high-risk (64.3% vs. 76.1%) and low-risk (35.3% vs. 45.5%) pregnant women from the modified enrichment group was slightly lower than those from the conventional group, though no significant difference was detected. There was one false negative case for trisomy 21 among the high-risk pregnant women from the conventional group, and no false negative case was found in the modified enrichment group. Conclusion:The modified technique to screen and enrich the cffDNA has significantly enhanced the relative concentration of cffDNA and reduced the failure and duplication detection rate of NIPT, which has significantly reduced the incidence of false negative cases due to the low concentration of cffDNA, and greatly increased the overall detection efficacy of NIPT.

Objective:To evaluate the value of modified magnetic bead screening for enrichment of cell-free fetal DNA (cffDNA) in non-invasive prenatal testing (NIPT).Methods:This study retrospectively recruited 31 cases with low concentration of cffDNA (<6.00%), Z value in the gray zone (3.00-4.00) at the first detection, or false-positive (confirmed by invasive prenatal diagnosis) or false-negative (confirmed by postnatal chromosome test) results among 11 000 pregnant women who underwent routine NIPT in Beijing Haidian District Maternal and Child Health Care Hospital from October 2017 to December 2019. Plasma samples collected for the first-time routine NIPT were used to enrich cffDNA using modified magnetic beads for NIPT (modified NIPT). Wilcoxon rank sum test was used to compare the modified NIPT with the routine NIPT in detecting the cffDNA concentrations of male fetuses.Results:Among the 31 pregnant women, there were 13 cases with low cffDNA concentration in routine NIPT, 11 having false-positive results in the routine NIPT (three for trisomy 13, four for trisomy 18 and four for trisomy 21, all were confirmed by invasive prenatal diagnosis), six with gray-zone Z values in the first-time NIPT (retesting indicating low risk) and one having false negative result for trisomy 21 (confirmed by postnatal chromosome test). Cell-free DNA (cfDNA) fragments less than 150 bp were effectively enriched using the modified magnetic bead screening and the concentration of cffDNA was increased from 4.43% (2.45%-17.61%) in routine NIPT to 13.46% (7.75%-36.64%) in the modified NIPT ( Z=-14.22, P<0.01). Results of the modified NIPT indicated that 13 cases with low cffDNA concentration of routine NIPT were successfully detected as low risk, as well as the risks in the six cases with gray-zone Z value and six of the 11 false-positive cases in the routine NIPT were low, which were consistent with the retest results of the routine NIPT, while high risk was found in one false-negative case. Conclusions:The modified NIPT could reduce the false positive rate by lowering the failure rate caused by low concentration of cffDNA and is able to identify false-negative cases. Compared with the routine NIPT, it shows a higher success rate and a lower false positive rate.

Objective To search for novel potent 3-ester derivatives of arenobufagin and test their antitumor activities in vitro. Methods Target compounds were synthesized by esterification of arenobufagin with acids. CellTiter method was used to assay the in vitro antitumor activities. Results 3-Ester derivatives exhibited excellent antitumor activities against all the cancer cells. Conclusion Among the 3-ester derivatives, compound 2a had the best activities with the IC₅₀ of 4.0−91.7 nmol/L and appeared to be a valuable candidate for further study.

Objective: To evaluate the long-term effect and safety of chrono-chemotherapy combined with intensity modulated radiotherapy (IMRT) in locally advanced nasopharyngeal carcinoma (NPC). Methods: 160 patients with locally advanced NPC were randomly divided into a chrono group and conventional group according to random number table. In the first stage, all patients underwent two cycles of induced chemotherapy, consisting of docetaxel, cisplatin and 5-Fu every 21 days. Notably, patients received chrono-moduated chemotherapy according to circadian rhythm in the chrono group, and conventional chemotherapy in the conventional group. Then, 21 days after the completion of first stage, three cycles of concurrent cisplatin chemotherapy every 21 days were given to all patients during IMRT. The median follow-up after the completion of radiotherapy was 31 months. Long-term side effects and the survival of patients were observed. Results: Patients in the chrono group had significantly lower rates of hearing loss (22.72%), dysphagia (0) and neck fibrosis (4.54%) compared with those in the conventional group (39.13%、8.69%, 15.94%, respectively, all P<0.05). Meanwhile, the 1- year overall survival rates (97.0% vs 92.8%), 3-year overall survival rates (80.3% vs 81.2%), 1-year progression free survival rates (95.5% vs 87.0%), 3-year progression free survival rates (71.2% vs 73.9%), 1-year locoregional relapse-free survival rates (97.0% vs 95.7%), 1-year locoregional relapse-free survival rates (92.4% vs 92.8%), 1-year distant metastasis-free survival rates (97.0% vs 98.6%) and 3-year distant metastasis-free survival rates (90.9% vs 91.3%) between the chrono group and the conventional group were not statistically significant (all P>0.05). Conclusions Compared with conventional chemotherapy, chrono-chemotherapy combined with IMRT didn′t affect long-term survival, but reducing the incidence of adverse events in patients with locally advanced NPC.

Silicon was once considered a biologically inert element, but recent research has shown its value for human health.Soluble silicic acid is the available form of silicon in human body. This paper reviews the absorption, distribution and metabolic characteristics of dietary soluble silicic acid in human body, as well as its relationship with human health.Available data show that it has lots of supporting evidences that dietary soluble silicic acid can prevent osteoporosis, maintain vascular health, improve the symptoms of Alzheimer's disease and multiple sclerosis.Its unique crosslinking ability and antagonism to toxic aluminum play a crucial role. In the early stage of human life, there is a strong demand for silicon, and the level of silicon in the aged is generally reduced, suggesting that pregnant women and old people should pay attention to the intake of soluble silicic acid. It is suggested to strengthen the basic and applied research on dietary soluble silicic acid,and gradually establish the relevant nutrition and hygiene standards.

Silicon was once considered a biologically inert element, but recent research has shown its value for human health.Soluble silicic acid is the available form of silicon in human body. This paper reviews the absorption, distribution and metabolic characteristics of dietary soluble silicic acid in human body, as well as its relationship with human health.Available data show that it has lots of supporting evidences that dietary soluble silicic acid can prevent osteoporosis, maintain vascular health, improve the symptoms of Alzheimer's disease and multiple sclerosis.Its unique crosslinking ability and antagonism to toxic aluminum play a crucial role. In the early stage of human life, there is a strong demand for silicon, and the level of silicon in the aged is generally reduced, suggesting that pregnant women and old people should pay attention to the intake of soluble silicic acid. It is suggested to strengthen the basic and applied research on dietary soluble silicic acid,and gradually establish the relevant nutrition and hygiene standards.