The theory of “diagnosing diseases with sinews” means that through the diagnosis and examination of the channel sinews at the site of the lesion， the surplus and deficit state of qi and blood in the channel sinews， vessles and channels， and the degree of damage to the organism caused by the disease and evils， can be determined， forming the three elements （the nature of the disease， the location of the disease， and the disease tendency） of the disease diagnosis can be closely integrated to form the trinity of diagnostic modes， which is “examining the disease nature by sinews， identifying the pattern by sinews， and determining the tendency by sinews”. For intractable facial paralysis， the method of “diagnosing diseases with sinews” can be adopted， in which the morphological changes of the channel sinews are judged through diagnosis by observation， the traditional Chinese patterns are identified through diagnosis by palpation， and the points of meridian tendons and the circulation of tendon and treatment lines are determined through diagnosis by circulation. The “diagnosing diseases with sinews” not only helps to accurately determine the disease condition， patterns and development trend， but also helps to adopt targeted treatment for the disease and prevent the disease from spreading， and providing ideas and methods for the clinical diagnosis and treatment of intractable facial paralysis.

OBJECTIVE To identify, synthesize and analyze the structure of unknown impurities unique to bromhexine hydrochloride injection and set the impurities as known impurity to control. METHODS The structure of unknown impurities was derived through two-dimensional liquid chromatography tandem mass spectrometry(2DLC-HRMS/MS), and the source of impurities was derived based on the product's prescription process. The mechanism of impurities generation was analyzed, and impurity monomers were obtained through directional synthesis. The structure of impurities was confirmed using techniques such as 2DLC-HRMS/MS and nuclear magnetic resonance. Finally, HPLC was used to verify the analysis method of impurities. RESULTS It was confirmed that such impurities were produced in a reaction between bromhexine and the excipient glucose. The correction factor of the two impurities were 2.2 and 2.4, the analytical method was specific and reproducible. CONCLUSION Name the two injection specific impurities as impurity 1 and impurity 2 respectively, and use them as known impurities to be included in the standard, calculate the impurity content using the self control and correction factor method. This study is of great significance in guiding the impurity control of bromhexine hydrochloride injection and the screening of excipient glucose.

Objective:To detect pathogenic mutation in a Chinese family affected with isolated bilateral microtia.Methods:During 2022 June to December, one Chinese Han family with non-syndromic bilateral microtia was recruited at the First Hospital of Shanxi Medical University. The clinical data and peripheral blood samples were collected from the family members. Whole genome sequencing (WGS) was performed in the proband to screen all candidate variants. Quantitative PCR was applied to identify the candidate copy number variation (CNV) among the proband, the unaffected wife and the affected son to demonstrate the association between candidate variant and phenotype.Results:The patients in the family had non-syndromic bilateral concha-type microtia. WGS detected the duplication in the intergenic region of HMX1 and CPZ gene in the proband, which involved the evolutionarily conserved region (ECR). Both the proband and his affected son carried the CNV, while his unaffected wife did not have this variation.Conclusion:Duplications involving the long range HMX1 enhancer ECR are associated with the bilateral concha-type microtia in this family.

Objective:To detect pathogenic mutation in a Chinese family affected with isolated bilateral microtia.Methods:During 2022 June to December, one Chinese Han family with non-syndromic bilateral microtia was recruited at the First Hospital of Shanxi Medical University. The clinical data and peripheral blood samples were collected from the family members. Whole genome sequencing (WGS) was performed in the proband to screen all candidate variants. Quantitative PCR was applied to identify the candidate copy number variation (CNV) among the proband, the unaffected wife and the affected son to demonstrate the association between candidate variant and phenotype.Results:The patients in the family had non-syndromic bilateral concha-type microtia. WGS detected the duplication in the intergenic region of HMX1 and CPZ gene in the proband, which involved the evolutionarily conserved region (ECR). Both the proband and his affected son carried the CNV, while his unaffected wife did not have this variation.Conclusion:Duplications involving the long range HMX1 enhancer ECR are associated with the bilateral concha-type microtia in this family.

Acupuncture and Tuina are the main non-drug therapies for low back pain, which are recommended by the guidelines. Acupuncture and Tuina can alleviate pain, which is regarded as conditional specific outcome, and improve mental, emotional problems, as non-conditional specific outcomes. There are some problems of the outcome assessment of acupuncture and Tuina treatment for pain such as insufficient evaluation of specific effect and unclear evaluation of characteristic outcome. Therefore, the key to above problems is to construct a Specific ouTcomE Assessment Modal of acupuncture and Tuina treatment for pain (STEAM-A&T) based on the qualitive and quantitative methods. By describing the experience, narrative expression, feelings and needs of patients who receiving acupuncture and Tuina treatment, the item banks of acupuncture and Tuina treatment effect are constructed, and the characteristic outcome of acupuncture and Tuina for pain will be screened, and then the relationship model among outcomes is constructed and optimized, which reflected the characteristics of acupuncture and Tuina for pain from multiple dimensions, multiple levels and multiple views. We reveal the relationship between the outcome of acupuncture and Tuina for pain. It will provide a new theory and methods for the construction of specific outcome assessment modal of Traditional Chinese Medicine.

Objective:To investigate the expression level, development mechanism, role and clinical prognostic significance of tweety homolog 2 (TTYH2) in cutaneous melanoma (SKCM).Methods:The expression data and clinical information of 365 cutaneous melanoma patients were downloaded from the Cancer Genome Atlas (TCGA), and the expression data of 812 normal tissues were retrieved from the genotype and Genotype-Tissue Expression(GTEx) to analyze the expression level of TTYH2 in SKCM tissues and normal counterparts. Survival analysis and Cox proportional hazard regression analysis were used to evaluate the effect of TTYH2 expression on prognosis and survival in SKCM patients. Gene set enrichment analysis Kyoto Genome Encyclopedia (KEGG) and Gene Ontology (GO) were used to screen signaling pathways for significant TTYH2 enrichment. The interaction network analysis was carried out using STRING online platform to screen key protein network node genes. Secondly, CIBERSORT algorithm was used to analyze the expression of 22 immune cells in each sample, and Chi-square test was applied to analyze the difference of immune cells in the high-low expression group.Results:The expression of TTYH2 in SKCM patients was significantly higher than that in normal tissues. Survival analysis showed that SKCM patients with high TTYH2 expression group had a poor prognosis. High TTYH2 expression was an independent predictor of poor overall survival of SKCM ( HR=1.21, 95% CI 1.08-1.37, P=0.001). KEGG result showed that TTYH2 was mainly concentrated in cell synapses, ion channels, calcium signaling pathways and extracellular matrix receptor interaction pathways. GO analysis showed that the biological processes involved in TTYH2 may be closely related to the occurrence and development of tumors. TTYH2 interacts with chloride intracellular channel protein 5, chloride ion channel protein 2, glycine receptor family members and gamma-aminobutyric acid receptor family members, suggesting that TTYH2 may play an important role in the pathogenesis of SKCM. Immune cell infiltration analysis showed that the immune cell abundance of memory B cells, CD4 memory T cells and monocytes was significantly increased in the TTYH2 low expression group, while the immune abundance of follicular helper T cells and regulatory T cells was significantly decreased in the TTYH2 low expression group. Conclusion:TTYH2 expression may regulate the development of SKCM cells through various ways, affect the survival and prognosis of SKCM patients, and is a potential biological prognostic marker and therapeutic target of SKCM.

Objective:To investigate the expression level, development mechanism, role and clinical prognostic significance of tweety homolog 2 (TTYH2) in cutaneous melanoma (SKCM).Methods:The expression data and clinical information of 365 cutaneous melanoma patients were downloaded from the Cancer Genome Atlas (TCGA), and the expression data of 812 normal tissues were retrieved from the genotype and Genotype-Tissue Expression(GTEx) to analyze the expression level of TTYH2 in SKCM tissues and normal counterparts. Survival analysis and Cox proportional hazard regression analysis were used to evaluate the effect of TTYH2 expression on prognosis and survival in SKCM patients. Gene set enrichment analysis Kyoto Genome Encyclopedia (KEGG) and Gene Ontology (GO) were used to screen signaling pathways for significant TTYH2 enrichment. The interaction network analysis was carried out using STRING online platform to screen key protein network node genes. Secondly, CIBERSORT algorithm was used to analyze the expression of 22 immune cells in each sample, and Chi-square test was applied to analyze the difference of immune cells in the high-low expression group.Results:The expression of TTYH2 in SKCM patients was significantly higher than that in normal tissues. Survival analysis showed that SKCM patients with high TTYH2 expression group had a poor prognosis. High TTYH2 expression was an independent predictor of poor overall survival of SKCM ( HR=1.21, 95% CI 1.08-1.37, P=0.001). KEGG result showed that TTYH2 was mainly concentrated in cell synapses, ion channels, calcium signaling pathways and extracellular matrix receptor interaction pathways. GO analysis showed that the biological processes involved in TTYH2 may be closely related to the occurrence and development of tumors. TTYH2 interacts with chloride intracellular channel protein 5, chloride ion channel protein 2, glycine receptor family members and gamma-aminobutyric acid receptor family members, suggesting that TTYH2 may play an important role in the pathogenesis of SKCM. Immune cell infiltration analysis showed that the immune cell abundance of memory B cells, CD4 memory T cells and monocytes was significantly increased in the TTYH2 low expression group, while the immune abundance of follicular helper T cells and regulatory T cells was significantly decreased in the TTYH2 low expression group. Conclusion:TTYH2 expression may regulate the development of SKCM cells through various ways, affect the survival and prognosis of SKCM patients, and is a potential biological prognostic marker and therapeutic target of SKCM.

Flash radiotherapy is a kind of radiotherapy method using ultra-high dose rate radiation. Compared with the traditional dose rate radiotherapy, it has unique radiobiological advantages. In this paper, the principle of flash radiotherapy, the process and results of biological experiments are summarized. At the same time, the advantages and challenges of flash radiotherapy are analyzed, and the future clinical application is prospected.
Radiotherapy/methods* ; Radiotherapy Dosage ; Technology

Objective:To summary the clinical features of 8 cases with ankylosing spondylitis (AS) complicated with systemic lupus erythematosus (SLE).Methods:This study was conducted retrospectively from January 2007 to November 2018. Eight patients with AS complicated with SLE who were admitted to Foshan Hospital of TCM were analyzed. Bath ankylosing spondylitis disease activity index (BASDAI) was compared using t-test. Results:Four patients were female. The mean age was (31±14) years, ranged from 16 to 59 years. The average disease duration of AS was (27±30) months(ranging from 4 to 144 months). The average disease of duration SLE was (69±51) months (ranging from 1 to 80 months). All patients was human lymphocyte antigen (HLA)-B27 positive. SLE-related organ involvement included kidney in 5 cases, leukocytopenia in 8 cases, arthralgia in 6 cases, nervous system in 1 case and skin rash in 3 cases. Renal biopsy were performed in 3 patients. And 2 cases were class Ⅲ+Ⅴ lupus nephritis, another one was class Ⅳ+Ⅴ lupus nephritis.Conclusion:AS may complicated with SLE. Some drugs may be able to active the potential SLE, which should be differentiated from drug-related lupus.

Objective To investigate the inter-hemispheric resting-state functional connectivity and its relation with cognitive function in patients with end-stage renal disease (ESRD) by using resting-state functional magnetic resonance imaging (rs-fMRI) based on voxel-mirrored homotopic connectivity (VMHC). Methods A total of 52 patients with ESRD (ESRD group), admitted to our hospital from July 2018 to January 2019, were enrolled; 36 age-, gender-, and education level-matched healthy controls (HCs group) were collected at the same time period. The cognitive function of all subjects was assessed by Mini Mental State Examination (MMSE), Montreal Cognitive Assessment (MoCA), Trail Making Test (TMT)-A, TMT-B and Symbol Digit Modalities Test (SDMT). The rs-fMRI and 3D-T1WI data were acquired from all subjects; after image preprocessing, VMHC values between brain hemispheres were calculated and the regions with significantly different VMHC values were obtained. The correlations between VMHC values in significant regions and cognitive scale scores were analyzed. Results MMSE, MoCA and SDMT scores of ESRD patients were significantly lower than those of the HCs group (P<0.05), and ESRD patients took longer time to complete TMT-A and TMT-B tests than the HCs group (P<0.05). As compared with that of the HCs group, significant decrease of VMHC values of ESRD patients was found in the hippocampus, lingual gyrus, superior temporal gyrus, caudate nucleus and anterior cingulate gyrus (P<0.01, AlphaSim correction); the VMHC values of the anterior cingulate gyrus and hippocampus were positively correlated with MMSE and MoCA scores (P<0. 05). Conclusion Significant abnormal inter-hemisphere functional connectivity is found in patients with ESRD, which is associated with cognitive function.