The experience of professor YANG Wen-Hui in treating lumbago disease with YANG's Baliao-acupoints moxibustion is introduced in this paper.YANG Wen-Hui believes that the basic pathogenesis of lumbago disease is'cold causes lower back pain',and based on the philosophical idea of'harmony in Shushu(the ways to cultivate health)',he proposes'YANG's Baliao-acupoints moxibustion'for the treatment of lumbago disease.According to the patient's condition,professor YANG used the acupoints of Shangliao(BL31),Ciliao(BL32),Zhongliao(BL33),and selected the moxa cone like jujube core,soybean or wheat grain,and applied moxibustion with the technique of'San Yang Kai Tai'or'Ruo feng Chui Yun',the number of moxibustion is proportional to the age of the patient.YANG's Baliao-acupoints moxibustion in treating lumbago disease exerts highly and remarkable clinical efficacy,and it was widely acclaimed by the patients.

Objective To establish a dynamic prediction model of fatal massive hemorrhage in trauma based on the vital signs time series data and machine learning algorithms.Methods Retrospectively analyze the vital signs time series data of 7522 patients with trauma in the Medical Information Mart for Intensive Care-Ⅳ(MIMIC-Ⅳ)database from 2008 to 2019.According to the occurrence of posttraumatic fatal massive hemorrhage,the patients were divided into two groups:fatal massive hemorrhage group(n=283)and non-fatal massive hemorrhage group(n=7239).Six machine learning algorithms,including logistic regression(LR),support vector machine(SVM),random forests(RF),adaptive boosting(AdaBoost),gated recurrent unit(GRU),and GRU-D were used to develop a dynamic prediction models of fatal massive hemorrhage in trauma.The probability of fatal massive hemorrhage in the following 1,2,and 3 h was dynamically predicted.The performance of the models was evaluated by accuracy,sensitivity,specificity,positive predictive value,negative predictive value,Youden index,and area under receiver operating characteristic curve(AUC).The models were externally validated based on the trauma database of the Chinese PLA General Hospital.Results In the MIMIC-Ⅳ database,the set of dynamic prediction models based on the GRU-D algorithm was the best.The AUC for predicting fatal major bleeding in the next 1,2,and 3 h were 0.946±0.029,0.940±0.032,and 0.943±0.034,respectively,and there was no significant difference(P=0.905).In the trauma dataset,GRU-D model achieved the best external validation effect.The AUC for predicting fatal major bleeding in the next 1,2,and 3 h were 0.779±0.013,0.780±0.008,and 0.778±0.009,respectively,and there was no significant difference(P=0.181).This set of models was deployed in a public web calculator and hospital emergency department information system,which is convenient for the public and medical staff to use and validate the model.Conclusion A set of dynamic prediction models has been successfully developed and validated,which is greatly significant for the early diagnosis and dynamic prediction of fatal massive hemorrhage in trauma.

Objective: To identify the risk factors in mortality of pediatric acute respiratory distress syndrome (PARDS) in pediatric intensive care unit (PICU). Methods: Second analysis of the data collected in the "efficacy of pulmonary surfactant (PS) in the treatment of children with moderate to severe PARDS" program. Retrospective case summary of the risk factors of mortality of children with moderate to severe PARDS who admitted in 14 participating tertiary PICU between December 2016 to December 2021. Differences in general condition, underlying diseases, oxygenation index, and mechanical ventilation were compared after the group was divided by survival at PICU discharge. When comparing between groups, the Mann-Whitney U test was used for measurement data, and the chi-square test was used for counting data. Receiver Operating Characteristic (ROC) curves were used to assess the accuracy of oxygen index (OI) in predicting mortality. Multivariate Logistic regression analysis was used to identify the risk factors for mortality. Results: Among 101 children with moderate to severe PARDS, 63 (62.4%) were males, 38 (37.6%) were females, aged (12±8) months. There were 23 cases in the non-survival group and 78 cases in the survival group. The combined rates of underlying diseases (52.2% (12/23) vs. 29.5% (23/78), χ²=4.04, P=0.045) and immune deficiency (30.4% (7/23) vs. 11.5% (9/78), χ²=4.76, P=0.029) in non-survival patients were significantly higher than those in survival patients, while the use of pulmonary surfactant (PS) was significantly lower (8.7% (2/23) vs. 41.0% (32/78), χ²=8.31, P=0.004). No significant differences existed in age, sex, pediatric critical illness score, etiology of PARDS, mechanical ventilation mode and fluid balance within 72 h (all P>0.05). OI on the first day (11.9(8.3, 17.1) vs.15.5(11.7, 23.0)), the second day (10.1(7.6, 16.6) vs.14.8(9.3, 26.2)) and the third day (9.2(6.6, 16.6) vs. 16.7(11.2, 31.4)) after PARDS identified were all higher in non-survival group compared to survival group (Z=-2.70, -2.52, -3.79 respectively, all P<0.05), and the improvement of OI in non-survival group was worse (0.03(-0.32, 0.31) vs. 0.32(-0.02, 0.56), Z=-2.49, P=0.013). ROC curve analysis showed that the OI on the thind day was more appropriate in predicting in-hospital mortality (area under the curve= 0.76, standard error 0.05,95%CI 0.65-0.87,P<0.001). When OI was set at 11.1, the sensitivity was 78.3% (95%CI 58.1%-90.3%), and the specificity was 60.3% (95%CI 49.2%-70.4%). Multivariate Logistic regression analysis showed that after adjusting for age, sex, pediatric critical illness score and fluid load within 72 h, no use of PS (OR=11.26, 95%CI 2.19-57.95, P=0.004), OI value on the third day (OR=7.93, 95%CI 1.51-41.69, P=0.014), and companied with immunodeficiency (OR=4.72, 95%CI 1.17-19.02, P=0.029) were independent risk factors for mortality in children with PARDS. Conclusions: The mortality of patients with moderate to severe PARDS is high, and immunodeficiency, no use of PS and OI on the third day after PARDS identified are the independent risk factors related to mortality. The OI on the third day after PARDS identified could be used to predict mortality.
Female ; Male ; Humans ; Child, Preschool ; Infant ; Child ; Critical Illness ; Pulmonary Surfactants/therapeutic use* ; Retrospective Studies ; Risk Factors ; Respiratory Distress Syndrome/therapy*

OBJECTIVE: This study was aimed at investigating the carrier rate of, and molecular variation in, α- and β-globin gene mutations in Hunan Province. METHODS: We recruited 25,946 individuals attending premarital screening from 42 districts and counties in all 14 cities of Hunan Province. Hematological screening was performed, and molecular parameters were assessed. RESULTS: The overall carrier rate of thalassemia was 7.1%, including 4.83% for α-thalassemia, 2.15% for β-thalassemia, and 0.12% for both α- and β-thalassemia. The highest carrier rate of thalassemia was in Yongzhou (14.57%). The most abundant genotype of α-thalassemia and β-thalassemia was -α ^3.7/αα (50.23%) and β ^IVS-II-654/β ^N (28.23%), respectively. Four α-globin mutations [CD108 (ACC>AAC), CAP +29 (G>C), Hb Agrinio and Hb Cervantes] and six β-globin mutations [CAP +8 (C>T), IVS-II-848 (C>T), -56 (G>C), beta nt-77 (G>C), codon 20/21 (-TGGA) and Hb Knossos] had not previously been identified in China. Furthermore, this study provides the first report of the carrier rates of abnormal hemoglobin variants and α-globin triplication in Hunan Province, which were 0.49% and 1.99%, respectively. CONCLUSION Our study demonstrates the high complexity and diversity of thalassemia gene mutations in the Hunan population. The results should facilitate genetic counselling and the prevention of severe thalassemia in this region.
Humans ; beta-Thalassemia/genetics* ; alpha-Thalassemia/genetics* ; Hemoglobinopathies/genetics* ; China/epidemiology* ; High-Throughput Nucleotide Sequencing

ObjectiveTo observe the effects of fire-needle of Lingnan on the vitiligo model after hydroquinone-induced oxidative stress based on the Hippo-YAP signaling pathway. MethodsC57BL/6 mice were randomly divided into normal group （Control）， model group （HQ）， HQ+fire-needle group （FA）， and positive control group （Halometasone）， with 8 mice in each group. The vitiligo model was prepared by hydroquinone （HQ）. The skin pathological changes were observed by depigmentation score， HE staining and Masson-Fontana. Elisa was used to detect the levels of tyrosinase （TYR）， malondialdehyde （MDA） and monoamine oxidase （MAO）.Western-blot and PCR were used to detect the expression of Yap1 and Tp73 among the groups. ResultsCompared with the control group， the epidermis and dermis were significantly thicker. The number of melanocyte hair follicles， basal melanocytes， epidermal cells containing melanin granules were significantly decreased， and the depigmentation score was significantly reduced（P＜0.01）. The level of TYR decreased， and the levels of MDA and MAO increased after modeling（P＜0.01）. The expression of Yap1 and Tp73 were significantly reduced （P<0.01）. The dermis became thinner in the halometasone and FA group after treatment of 4 weeks. The number of melanocyte hair follicles， basal melanocytes， epidermal cells containing melanin granules increased （P<0.05）. Compared with that of the HQ group， the level of TYR in the halometasone group and FA group was significantly increased （P<0.01）. The levels of MDA and MAO in the FA group were decreased （P<0.05）. The expressions of Yap1 and Tp73 in the FA group were significantly increased （P<0.01）， and their effects were better than those in the Halometasone group （P<0.05）. ConclusionsFire-needle of Lingnan protects melanocytes from oxidative stress by activating the Hippo-YAP pathway. It enhances the synthesis and function of melanocytes and promotes repigmentation by reducing the content and activity of oxidative stress products.

ObjectiveTo establish a quantitative analysis multi-components by single marker method （QAMS） for five main components （aucubin， geniposidic acid， chlorogenic acid， asperuloside and rutin） in Eucommiae Folium， to verify its feasibility and applicability in the determination of Eucommiae Folium， so as to provide a scientific basis for the development of quality standard of this herb. MethodHigh performance liquid chromatography was performed on a Welch Boltmatetm™ C₁₈ column （4.6 mm×100 mm， 2.7 μm） with methanol （A）-0.2% phosphoric acid aqueous solution （B） as the mobile phase for gradient elution （0-8 min， 3%A； 8-10 min， 3%-11%A； 10-26 min， 11%A； 26-27 min， 11%-25%A； 27-60 min， 25%-32%A）， the column temperature was set at 30 ℃， the flow rate was 0.6 mL·min^-1， the detection wavelengths were at 210 nm and 254 nm. Chlorogenic acid was used as an internal reference to establish the relative correction factors （f） between it and the other four components， and the contents of the five components in 14 batches of Eucommiae Folium were determined by QAMS and external standard method （ESM）， respectively. ResultThe f values of chlorogenic acid to aucubin， geniposidic acid， asperuloside and rutin were 3.13， 1.45， 2.64 and 0.56， respectively. Repeatability was good under different experimental conditions， relative standard deviation （RSD） was <5.0%. The contents of aucubin， geniposidic acid， chlorogenic acid， asperuloside and rutin in 14 batches of Eucommiae Folium were 1.340-28.975， 0.252-36.086， 10.016-27.443， 1.396-8.646， 0.533-1.766 mg·g^-1， respectively. There were no significant difference between content results of QAMS and that of ESM （RSD<5.0%）. ConclusionQAMS established with chlorogenic acid as the internal reference can be used to determine the contents of five components in Eucommiae Folium， and this method is simple and accurate. After comprehensive evaluation， the quality standard of Eucommiae Folium in subsequent editions of Chinese Pharmacopoeia is suggested that three main active components， chlorogenic acid， aucubin and geniposidic acid， are selected as quality markers， and their content limits are recommended not less than 1.5%， 1.0% and 1.0%， respectively. This quality standard draft can avoid the potential quality risk due to poor specificity and low content limit of the index component （chlorogenic acid） in the previous editions of Chinese Pharmacopoeia.

OBJECTIVE: To explore the brain effect mechanism and the correlation between brain functional imaging and cognitive function in treatment of depressive disorder (DD) with transcutaneous auricular vagus nerve stimulation (taVNS) based on the resting-state functional magenetic reasonance imaging (rs-fMRI). METHODS: Thirty-two DD patients were included in a depression group and 32 subjects of healthy condition were enrolled in a normal group. In the depression group, the taVNS was applied to bilateral Xin (CO₁₅) and Shen (CO₁₀), at disperse-dense wave, 4 Hz/20 Hz in frequency and current intensity ≤20 mA depending on patient's tolerance, 30 min each time, twice daily. The duration of treatment consisted of 8 weeks. The patients of two groups were undertaken rs-fMRI scanning. The scores of Hamilton depression scale (HAMD), Hamilton anxiety scale (HAMA) and Wisconsin card sorting test (WCST) were observed in the normal group at baseline and the depression group before and after treatment separately. The differential brain regions were observed before and after treatment in the two groups and the value of degree centrality (DC) of fMRI was obtained. Their correlation was analyzed in terms of HAMD, HAMA and WCST scores. RESULTS: The scores of HAMD and HAMA in the depression group were all higher than those in the normal group (P<0.05). After treatment, the scores of HAMD and HAMA were lower than those before treatment in the depression group; the scores of total responses, response errors and perseverative errors of WCST were all lower than those before treatment (P<0.05). The brain regions with significant differences included the left inferior temporal gyrus, the left cerebellar peduncles region 1, the left insula, the right putamen, the bilateral supplementary motor area and the right middle frontal gyrus. After treatment, the value of DC in left supplementary motor area was negatively correlated to HAMD and HAMA scores respectively (r=-0.324, P=0.012; r=-0.310, P=0.015); the value of DC in left cerebellar peduncles region 1 was negatively correlated to the total responses of WCST (r=-0.322, P=0.013), and the left insula was positively correlated to the total responses of WCST (r=0.271, P=0.036). CONCLUSION The taVNS can modulate the intensity of the functional activities of some brain regions so as to relieve depressive symptoms and improve cognitive function.
Humans ; Depression/therapy* ; Magnetic Resonance Imaging/methods* ; Vagus Nerve Stimulation/methods* ; Brain/diagnostic imaging* ; Transcutaneous Electric Nerve Stimulation/methods* ; Vagus Nerve

Objective: To analyze and compare therapy responses, outcomes, and incidence of severe hematologic adverse events of flumatinib and imatinib in patients newly diagnosed with chronic phase chronic myeloid leukemia (CML) . Methods: Data of patients with chronic phase CML diagnosed between January 2006 and November 2022 from 76 centers, aged ≥18 years, and received initial flumatinib or imatinib therapy within 6 months after diagnosis in China were retrospectively interrogated. Propensity score matching (PSM) analysis was performed to reduce the bias of the initial TKI selection, and the therapy responses and outcomes of patients receiving initial flumatinib or imatinib therapy were compared. Results: A total of 4 833 adult patients with CML receiving initial imatinib (n=4 380) or flumatinib (n=453) therapy were included in the study. In the imatinib cohort, the median follow-up time was 54 [interquartile range (IQR), 31-85] months, and the 7-year cumulative incidences of CCyR, MMR, MR(4), and MR(4.5) were 95.2%, 88.4%, 78.3%, and 63.0%, respectively. The 7-year FFS, PFS, and OS rates were 71.8%, 93.0%, and 96.9%, respectively. With the median follow-up of 18 (IQR, 13-25) months in the flumatinib cohort, the 2-year cumulative incidences of CCyR, MMR, MR(4), and MR(4.5) were 95.4%, 86.5%, 58.4%, and 46.6%, respectively. The 2-year FFS, PFS, and OS rates were 80.1%, 95.0%, and 99.5%, respectively. The PSM analysis indicated that patients receiving initial flumatinib therapy had significantly higher cumulative incidences of CCyR, MMR, MR(4), and MR(4.5) and higher probabilities of FFS than those receiving the initial imatinib therapy (all P<0.001), whereas the PFS (P=0.230) and OS (P=0.268) were comparable between the two cohorts. The incidence of severe hematologic adverse events (grade≥Ⅲ) was comparable in the two cohorts. Conclusion: Patients receiving initial flumatinib therapy had higher cumulative incidences of therapy responses and higher probability of FFS than those receiving initial imatinib therapy, whereas the incidence of severe hematologic adverse events was comparable between the two cohorts.
Adult ; Humans ; Adolescent ; Imatinib Mesylate/adverse effects* ; Incidence ; Antineoplastic Agents/adverse effects* ; Retrospective Studies ; Pyrimidines/adverse effects* ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive/drug therapy* ; Treatment Outcome ; Benzamides/adverse effects* ; Leukemia, Myeloid, Chronic-Phase/drug therapy* ; Aminopyridines/therapeutic use* ; Protein Kinase Inhibitors/therapeutic use*

Titin, the largest known protein in the body expressed in three isoforms (N2A, N2BA and N2B), is essential for muscle structure, force generation, conduction and regulation. Since the 1950s, muscle contraction mechanisms have been explained by the sliding filament theory involving thin and thick muscle filaments, while the contribution of cytoskeleton in force generation and conduction was ignored. With the discovery of insoluble protein residues and large molecular weight proteins in muscle fibers, the third myofilament, titin, has been identified and attracted a lot of interests. The development of single molecule mechanics and gene sequencing technology further contributed to the extensive studies on the arrangement, structure, elastic properties and components of titin in sarcomere. Therefore, this paper reviews the structure, isforms classification, elastic function and regulatory factors of titin, to provide better understanding of titin.
Connectin/genetics* ; Muscle Proteins/metabolism* ; Protein Isoforms/genetics* ; Sarcomeres/metabolism* ; Muscle Fibers, Skeletal/metabolism*

AIM: To investigate the protective effect of salvianolic acid B on retina and its influence on angiogenesis in retinal vein occlusion(RVO)injured rats.METHODS: SD rats were randomly divided into control group, model group and salvianolic acid B group, with 10 rats in each group. In addition to the control group, rats in model group and salvianolic acid B group were induced RVO by Bengal red combined with laser photodynamic method. The rats in salvianolic acid B group were intraperitoneally injected with salvianolic acid B 50 mg/(kg·d), while the rats in control group and model group were only given the same amount of normal saline for 21 consecutive days. Fundus fluorescein angiography(FFA)was used to observe the retinal vein structure before and after administration. HE staining was used to observe the pathological changes of rat retina. The retinal function of rats was evaluated by electroretinogram(ERG). The fluorescence expression of vascular endothelial growth factor A(VEGFA)in retina of rats in each group was detected by immunofluorescence staining. The relative expression of HIF-1α, STAT3, p-STAT3 and VEGFA proteins in retinal tissue were detected by Western blotting.RESULTS: Compared with the control group, the blood flow at the retinal obstruction in the model group was recanalized, and the effective collateral circulation was abundant, but the shape was irregular, and there was fluorescence leakage. In salvianolic acid B group, the retinal vein circulation recovered, the shape became regular gradually, and the collateral vessels decreased. The retina of the model group and salvianolic acid B group showed different degrees of pathological damage. At the same time, the amplitude of ERG a wave and b wave, the thickness of retinal total layer(RTL), inner nuclear layer(INL)and outer nuclear layer(ONL)decreased, the fluorescence intensity of VEGFA enhanced, and the relative expression of HIF-1α, p-STAT3 and VEGFA protein increased(P<0.05). Compared with the model group, the retinal histopathological damage of salvianolic acid B rats was alleviated, the amplitude of ERG a-wave and b-wave, the thickness of RTL, INL and ONL were increased, the fluorescence intensity of VEGFA was weakened, and the relative expression of HIF-1α, p-STAT3 and VEGFA proteins was decreased(P<0.05).CONCLUSION: Salvianolic acid B can alleviate the retinal histopathological injury and improve retinal function in RVO rats, which may be related to inhibiting the activation of HIF-1α/STAT3/VEGFA pathway and reducing angiogenesis.