Based on ultra-performance liquid chromatography-quadrupole-electrostatic field Orbitrap high-resolution mass spectrometry(UPLC-Q-Orbitrap HRMS) technology and molecular docking, the bitter-tasting substances(hereafter referred to as "bitter substances") in Cistanche deserticola extract were investigated, and the bitter taste and efficacy relationship was explored to lay the foundation for future research on de-bittering and taste correction. Firstly, UPLC-Q-Orbitrap HRMS was used for the qualitative analysis of the constituents of C. deserticola, and 69 chemical components were identified. These chemical components were then subjected to molecular docking with the bitter taste receptor, leading to the screening of 20 bitter substances, including 6 phenylethanol glycosides, 5 flavonoids, 3 phenolic acids, 2 cycloalkenyl ether terpenes, 2 alkaloids, and 2 other components. Nine batches of fresh C. deserticola samples were collected from the same origin but harvested at different months. These samples were divided into groups based on harvest month and plant part. The bitterness was quantified using an electronic tongue, and the content of six potential bitter-active compounds(pineconotyloside, trichothecene glycoside, tubulin A, iso-trichothecene glycoside, jinshihuaoside, and jingnipinoside) was determined by high-performance liquid chromatography(HPLC). The total content of phenylethanol glycosides, polysaccharides, alkaloids, flavonoids, and phenolic acids was determined using UV-visible spectrophotometry. Chemometric analyses were then conducted, including Pearson's correlation analysis, gray correlation analysis, and orthogonal partial least squares discriminant analysis(OPLS-DA), to identify the bitter components in C. deserticola. The results were consistent with the molecular docking findings, and the two methods mutually supported each other. Finally, network pharmacological predictions and analyses were performed to explore the relationship between the targets of bitter substances and their efficacy. The results indicated that key targets of the bitter substances included EGFR, PIK3CB, and PTK2. These substances may exert their bitter effects by acting on relevant disease targets, confirming that the bitter substances in C. deserticola are the material basis of its bitter taste efficacy. In conclusion, this study suggests that the phenylethanol glycosides, primarily pineconotyloside, mauritiana glycoside, and gibberellin, are the material basis for the "bitter taste" of C. deserticola. The molecular docking technique plays a guiding role in the screening of bitter substances in traditional Chinese medicine(TCM). The bitter substances in C. deserticola not only contribute to its bitter taste but also support the concept of the "taste-efficacy" relationship in TCM, providing valuable insights and references for future research in this area.
Molecular Docking Simulation ; Taste ; Chromatography, High Pressure Liquid ; Cistanche/chemistry* ; Drugs, Chinese Herbal/chemistry* ; Humans ; Mass Spectrometry

Objective:To perform molecular diagnosis and pedigree analysis for one case with α-thalassemia who does not conform to the genetic laws,and explore the effects of a newly discovered rare mutation(HBA2:c.*12G＞A)on clinical phenotypes.Methods:Blood samples of the proband and her family members were collected for blood routine analysis,and the hemoglobin components were analyzed by capillary electrophoresis.The common α-and β-globin gene loci in Chinese population were detected by conventional techniques(Gap-PCR,RDB-PCR).The α-globin gene sequences(HBA1,HBA2)were analyzed by Sanger sequencing.Results:By analyzing the test results of proband and her family members,the genotype of the proband was-α3,7/HBA2:c.*12G＞A,her father was HBA2:c.*12G＞A heterozygous mutation carrier.Conclusion:This study identifies a rare α-globin gene mutation(HBA2:c.*12G＞A)that has not been reported before.It is found that heterozygous mutation carriers present with static α-thalassemia.

OBJECTIVE: To monitor the changes of voriconazole minimum concentration(C_min) in patients with hematological diseases, and evaluate the factors influencing and adverse reactions of voriconazole clearance in patients with hematological diseases, so as to provide a theoretical basis for reasonable clinical use of voriconazole. METHODS: 136 patients with hematological diseases who used voriconazole in Wuhan NO.1 Hospital from May 2018 to December 2019 were selected. The correlation between C-reactive protein, albumin, creatinine and voriconazole C_min were analyzed, and the changes of voriconazole C_min after glucocorticoid treatment was also detected. In addition, stratified analysis was used to explore the adverse events of voriconazole. RESULTS: Among 136 patients, 77 were male (56.62%) and 59 were female (43.38%). There were positive correlations between voriconazole C_min and C-reactive protein and creatinine levels (r=0.277, r=0.208), while voriconazole C_min was negatively correlated with albumin level (r=-2.673). Voriconazole C_min in patients treated with glucocorticoid was decreased significantly (P<0.05). In addition, sratified analysis of voriconazole C_min showed that compared with voriconazole C_min 1.0-5.0 mg/L group, the incidence of adverse reactions of visual impairment in voriconazole C_min> 5.0 mg/L group was increased (χ²=4.318, P=0.038). CONCLUSION The levels of C-reactive protein, albumin and creatinine are closely related to the voriconazole C_min, which indicate that inflammation and hyponutrition may prevent the clearance of voriconazole in patients with hematological diseases. It is necessary to monitor the voriconazole C_min of patients with hematological diseases, and adjust the dosage in time to reduce adverse reactions.
Humans ; Male ; Female ; Voriconazole/therapeutic use* ; Antifungal Agents/therapeutic use* ; C-Reactive Protein ; Creatinine ; Glucocorticoids ; Retrospective Studies ; Drug Monitoring ; Hematologic Diseases

Although there is guidance from different regulatory agencies, there are opportunities to bring greater consistency and stronger applicability to address the practical issues of establishing and operating a data monitoring committee (DMC) for clinical studies of Chinese medicine. We names it as a Chinese Medicine Data Monitoring Committee (CMDMC). A panel composed of clinical and statistical experts shared their experience and thoughts on the important aspects of CMDMCs. Subsequently, a community standard on CMDMCs (T/CACM 1323-2019) was issued by the China Association of Chinese Medicine on September 12, 2019. This paper summarizes the key content of this standard to help the sponsors of clinical studies establish and operate CMDMCs, which will further develop the scientific integrity and quality of clinical studies.

OBJECTIVE: To proceed the clinical evaluation of DNA microarray for thalassemia gene detection. METHODS: Peripheral blood samples of 166 thalassemia gene test subjects were collected and tested for thalassemia genes by microarray chip method and Gap-PCR method combined with PCR-reverse dot blot hybridization method according to double-blind control test. The specificity, sensitivity, positive predictive value, negative predictive value, and total coincidence rate of the microarray chip method were evaluated. When the two methods were inconsistent, multiplex ligation dependent probe amplification (MLPA) was used to verify the deletional α-thalassemia. RESULTS: Compared with Gap-PCR method, specificity, sensitivity, positive predictive value, negative predictive value, Youden index, and total coincidence rate of microarray chip method was 100% (70/70), 96.88% (93/96), 100% (93/93), 95.89% (70/73), 0.969, and 97.59% (162/166), respectively, while compared with PCR-reverse dot blot hybridization method was 100% (125/125), 100% (41/41), 100% (41/41), 100% (125/125), 1, and 100% (166/166), respectively. CONCLUSION The microarray chip method for α-thalassemia gene detection shows the advantages of high specificity, sensitivity, and throughput.
Genetic Testing ; Humans ; Multiplex Polymerase Chain Reaction ; Oligonucleotide Array Sequence Analysis ; alpha-Thalassemia/genetics*

OBJECTIVE: To perform dried blood spots thalassemia gene detection in patients with positive blood phenotypes by microarray technology, and evaluate its value in clinical detection. METHODS: DNA samples were extracted from dried blood spots of 410 patients. Microarray technology was used to detect 3 deletion and 3 non-deletion types of α-thalassemia and 19 β-thalassemia point mutations which were common gene mutions in China. RESULTS: There were 357 positive cases in all the 410 tested samples with the positive rate 87.07%, among which 299 cases (72.93%) carried deletion or point mutations of α-thalassemia, 29 cases (7.07%) carried point mutations of β-thalassemia and 29 cases (7.07%) carried gene mutations of complex αβ-thalassemia syndrome. The mutations of α-thalassemia were involved with -- CONCLUSION The most common genetic mutations are --
China ; Humans ; Mutation ; Oligonucleotide Array Sequence Analysis ; alpha-Thalassemia/genetics* ; beta-Thalassemia/genetics*

Objective To observe the clinical efficacy and safety of flupentixol and melitracen tablets combined with psychological intervention in the treatment of cerebral infarction with anxiety disorder.Methods Eighty patients with cerebral infarction and anxiety disorders were randomly divided into control group and treatment group with 40 cases per group.Control group was treated with antiplatelet aggregation,activating blood stasis and brain protectant and so on.Treatment group was treated with flupentixol and melitracen tablet 10 mg per group,bid,orally,and psychological intervention once every 3-5 days,on the basis of control group.Two groups were treated for 6 weeks.The self rating scale (SAS)scores,depression self rating scale (SDS) scores,the United States national institutes of health stroke scale (NIHSS) scores and adverse drug reactions were compared between two groups.Results After treatment,the main indexes in treatment and control groups were compared:SAS scores were (40.07 ± 3.02) and (52.07 ± 6.94) points,SDS scores were (40.03 ±3.38) and (51.48 ± 7.22) points,NIHSS scores were (6.04 ± 1.51) and (8.92 ± 4.12) points,the differences were statistically significant (all P ＜ 0.05).No adverse drug reactions in two groups occurred during the treatment.Conclusion Flupentixol and melitracen tablets combined with psychological intervention have a definitive clinical efficacy and safety in the treatment of cerebral infarction with anxiety disorder,which can significantly reduce the NIHSS scores and improve prognosis.

X-linked ichthyosis (XLI) is a metabolic disease with steroid sulfatase deficiency and often occurs at birth or shortly after birth. The encoding gene of steroid sulfatase, STS, is located on the short arm of the X chromosome, and STS deletion or mutation can lead to the development of this disease. This study collected the data on the clinical phenotype from a family, and the proband, a boy aged 11 years with full-term vaginal delivery, had dry and rough skin and black-brown scaly patches, mainly in the abdomen and extensor aspect of extremities. Peripheral blood samples were collected from each family member and DNA was extracted. Multiplex ligation-dependent probe amplification (MLPA) was used to measure the copy number of STS on the X chromosome. Whole-genome microarray was used to determine the size of the segment with microdeletion in the X chromosome. MLPA was then used for prenatal diagnosis for the mother of the proband. The results revealed that the proband and another two male patients had hemizygotes in STS deletion. Gene microarray identified a rare deletion with a size of 1.6 Mb at Xp22.31 (chrX: 6,516,735-8,131,442). Two female family members were found to be carriers. Prenatal diagnosis showed that the fetus carried by the proband's mother was a carrier of this microdeletion. This study showed STS gene deletion in this family of XLI, which causes the unique skin lesions of XLI. MLPA is a convenient and reliable technique for the molecular and prenatal diagnosis of XLI.
Child ; Humans ; Ichthyosis, X-Linked ; diagnosis ; genetics ; Male ; Mutation ; Polymorphism, Single Nucleotide ; Prenatal Diagnosis ; Steryl-Sulfatase ; genetics

Objective To evaluate the feasibility and effectiveness of secundum atrial septal defect(ASD)occlusion with the septal occluder through right-chest small incision. Methods The clinical data of 140 secundum ASD patients (47 males and 93 females) aged 3-63 years who were treated in our center from August 2004 to July 2014 were retrospectively analyzed. The diameter of ASD was 6 to 36 mm. Under general anesthesia, all patients underwent intraoperative transtsophageal echocardiography (TEE), during which no associated cardiac deformity was found. All patients received ASD occlusion via a small incision (3-4 cm) at the right anterior chest. The occluders were released with the help of TEE. Results The atrial septal defect closure was successfully completed in 134 cases. Six cases received surgical closure of ASD after the failure of occlusion. The reasons of conversion included postoperative dislodgement of occlusion device (n=2, both were central type with large size) and technically unsuitable for occlusion (n=4, in whom residual shunt was found in 2 case, sieve pore type in 1 case, and intraoperative dislodgement in 1 case). All of these 6 patients were treated surgically under cardiopulmonary bypass. No dislocation of the device or atrial shunt was found within 3 to 48 months after the operation. Conclusion Occlusion via small chest incision of ASD under TEE guidance without cardiopulmonary bypass is a safe, minimally invasive, effective, and convenient treatment and worth clinical application.
Adolescent ; Adult ; Anesthesia, General ; Cardiopulmonary Bypass ; Child ; Child, Preschool ; Echocardiography ; Female ; Heart Septal Defects, Atrial ; surgery ; Humans ; Male ; Middle Aged ; Retrospective Studies ; Septal Occluder Device ; Treatment Outcome ; Young Adult

Objective To investigate the drug -metabolizing enzyme gene cytochrome P450 2C9 ( CYP2C9 ) distribution in Chinese Korean healthy population .Methods Two hundred healthy volunteers from Chi-nese Korean were recruited .A polymerase chain reaction -restriction fragment length polymorphism ( PCR-RFLP) method was developed to detect CYP2 C9*2 and *13 allele frequencies and compare genetic po-lymorphism differences with other ethnic groups from literatures .Results Six cases of CYP2C9 *1/*2 mutation individuals , 1 case of CYP2C9*2/*2 mutation individual and 1 case of CYP2C9*1/*13 mutated individuals in Korean health subjects were found in this study . The allele frequencies of CYP2C9*2 and *13 gene were 2.98% and 0.37%respectively.The results showed that there were similar ethnic in the distribution of CYP2C9 in Chinese Korean and Mongolian. Conclusion The results showed that Chinese Korean existed CYP 2C9 gene polymorphism distribution , and the distribution was similar to the Mongolian in Chifeng region .