This article summarized the current status and challenges of manipulation therapy for musculoskeletal pain and its placebo effect in clinical trials, analyzing the impact of the placebo effect on the evaluation of therapeutic efficacy. The efficacy of different manual manipulation techniques remains uncertain, and the degree of blinding and patient expectations play a crucial role in efficacy assessment. The article suggested improving trial design through standardized placebo intervention design, comprehensive investigation of patient expectations and psychological states, rigorous training of practitioners, and optimized diagnostic and treatment scenarios and doctor-patient relationship, to ensure consistency between intervention and placebo groups. Specific measures include the application of the DITTO (Deconstruct, Identify, Take out, Think, Optimize) framework, the use of standardized questionnaire tools, and multi-center, large-sample randomized controlled trials to enhance the external validity and statistical power of research results, thereby providing more scientifically reliable evidence for clinical practice.

Objective To explore the efficacy of carotid color Doppler ultrasonography(CDU)combined with transcranial color Doppler ultra sonography(TCCD)in the diagnosis of carotid artery stenosis in elderly patients with acute cerebral infarction(ACI).Methods The clinical data of 306 elderly patients with suspected ACI who were admitted to the Second Affiliated Hospital of Air Force Medical University,and received CDU and TCCD from May 2021 to May 2023 were retrospectively analyzed.The result of digital subtraction angiography(DSA)was taken as the gold standard.The patients were assigned to cerebral infarction group or non-cerebral infarction group according to the gold standard.CDU parameters(peak systolic velocity[PSV]and end diastolic velocity[EDV]of the common carotid artery])and TCCD parameters(resistance index[RI]and pulsatility index[PI]of posterior cerebral artery[PCA])were compared between the two groups.According to the degree of carotid artery stenosis,ACI patients were assigned to mild stenosis subgroup,moderate stenosis subgroup or severe stenosis subgroup.CDU parameters(PSV,EDV)and TCCD parameters(RI,PI)were compared among subgroups.The efficacy of related parameters in the diagnosis of ACI and the degree of carotid artery stenosis was evaluated by receiver operating characteristic(ROC)curve.Results There were 155 patients(50.65%)in the cerebral infarction group and 151 patients(49.35%)in the non-cerebral infarction group.The cerebral infarction group had higher EDV,PSV and RI and lower PI than the non-cerebral infarction group(P＜0.05).The areas under curve(AUC)values of ROC curves of EDV,PSV,RI,PI and their combination in the diagnosis of ACI were 0.577,0.563,0.644,0.643 and 0.726(P＜0.05).The levels of EDV,PSV and RI in the subgroups were as follows:severe stenosis subgroup＞moderate stenosis subgroup＞mild stenosis subgroup,and the change trend of PI was shown as mild stenosis subgroup＞moderate stenosis subgroup＞severe stenosis subgroup(P＜0.05).The AUC values of ROC curves of EDV,PSV,RI,PI and their combination in evaluating the degree of carotid artery stenosis in ACI patients were 0.767,0.802,0.845,0.846 and 0.952(P＜0.05).Conclusion Carotid CDU combined with TCCD can effectively diagnose ACI and carotid artery stenosis,and has high application value for the evaluation of carotid artery stenosis in elderly ACI patients.

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.

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 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