Fabry disease, a rare genetic disorder affecting multiple organs, has understudied correlations among enzyme activity, genotype, and clinical manifestations in patients of different sexes with classical and late-onset phenotypes. In this study, clinical data, α-Gal A activity, and GLA gene test results of 311 patients, who were categorized by classical and late-onset phenotypes, ⩽5% and > 5% of the normal mean value of enzyme activity, and truncated and nontruncated mutation groups, were collected. The common clinical manifestations of Fabry disease included acroparesthesia, hypohidrosis/anhidrosis, neuropsychiatric system, and renal and cardiovascular involvement. Multiorgan involvement was higher in males and classical phenotype patients. In both sexes, classical patients commonly presented with acroparesthesia and multiorgan involvement, whereas late-onset patients showed renal, neuropsychiatric, and cardiovascular involvement. Male and classical patients had lower enzyme activity than female and late-onset patients, respectively. Classical males with enzyme activity of ⩽5% of the normal mean level showed higher multiorgan involvement frequency than those with enzyme activity of > 5%, whereas no significant difference was observed among females. Ninety-five gene mutation sites were detected, with significant phenotype heterogeneity in patients with the same mutation. No significant difference in enzyme activity or clinical manifestations was observed between truncated and nontruncated mutations. Overall, male patients with Fabry disease, regardless of classical or late-onset phenotype, have a higher frequency of multiple-organ involvement and lower α-Gal A activity than female patients. α-Gal A activity was closely correlated with clinical symptoms in males but weakly correlated with clinical manifestations in females. The clinical manifestations of patients with the same mutation are heterogeneous, and the correlation between gene mutation and enzyme activity or clinical manifestation is weak.
Adolescent ; Adult ; Aged ; Female ; Humans ; Male ; Middle Aged ; Young Adult ; Age of Onset ; alpha-Galactosidase/metabolism* ; China ; Fabry Disease/enzymology* ; Genotype ; Mutation ; Phenotype ; Sex Factors ; East Asian People/genetics*

Fascia,the initial response site for mechanical stimulation in manipulations,is also the target of the effect of manipulations.As the essence of manipulation is"force",how mechanical stimuli are transduced into neuroelectric and biochemical signals in the fascia and how physical and chemical signals of the fascia initiate the mechanical stimulation effect are the common key questions in the study of the principle of manipulation.The physical changes in the fascial connective tissue caused by the manipulation,such as the deformation and displacement of the fascial tissue,can act on the nerve end receptors in the fascial layer and generate neural electrical signals;they can also activate the mechanoreceptors on the fascial cell membrane and convert mechanical signals into chemical signals via mechanosensitive ion channel transduction,triggering a physicochemical coupling response in the fascial microenvironment and producing mechanical stimulation through neuro-endocrine-immune system pathways.The"mechanical force of manipulation"in the fascia is transmitted through the meridian to facilitate the body's perception and transmission of mechanical stimulation signals,indicating that the fascia is the"sensor"of coupled response to the physicochemical information of mechanical stimulation of manipulation.

Background and purpose:Esophageal carcinoma(ESCA)is one of the malignant tumors with high mortality rate,and the underlying mechanism of its development is largely unknown.CDC20 plays an important role in tumorigenesis,and its dysregulated expression is closely related to tumor occurrence and development.The expression of CDC20 is increased in a variety of tumors,and knocking down CDC20 can inhibit tumor cell proliferation.NLRP3 is the main component of the inflammasome,and inflammasome is also closely related to tumor occurrence and development.Here,our study aimed to investigate whether CDC20 promotes the proliferation of ESCA cells through NLRP3 and its regulatory mechanism.Methods:The expression levels of CDC20 and NLRP3 genes in ESCA patients were analyzed using The Cancer Genome Atlas(TCGA)detabase and GTEx public database.We collected clinical and pathological data and tissues from 80 ESCA patients at the First Affiliated Hospital of Xinxiang Medical College,and detected the protein expression of NLRP3 in ESCA patients through immunohistochemistry staining.This study was approved by the Ethics Committee of the First Affiliated Hospital of Xinxiang Medical College(Number:EC-021-137).We studied the effects of knocking down CDC20 and NLRP3 gene on the proliferation ability of esophageal squamous cell carcinoma cells EC9706 and KYSE150 using short hairpin RNA(shRNA)technology.Co-immunoprecipitation(Co-IP),proteasome inhibitors and ubiquitination experiments were used to detect whether CDC20 interacts with NLRP3,and to elucidate whether CDC20 regulates NLRP3 expression through the ubiquitination pathway.This study was approved by the Ethics Committee of the First Affiliated Hospital of Xinxiang Medical College(Number:EC-021-137).Results:The TCGA database analysis showed that the expression levels of CDC20 and NLRP3 mRNA were significantly higher in the cancer tissues of ESCA patients than in the adjacent tissues.The immunohistochemistry results further showed that compared with adjacent tissues,the protein expression levels of CDC20 and NLRP3 were increased in ESCA tissues.Knocking down CDC20 and NLRP3 genes inhibited the proliferation of ESCA cells.Co-IP,proteasome inhibitors and ubiquitination experiments confirmed that CDC20 interacted with NLRP3 through its leucine-rich repeat(LRR),and CDC20 stabilized its expression by promoting NLRP3 ubiquitination.Conclusion:CDC20 and NLRP3 are upregulated in ESCA tissues,and CDC20 stabilizes their expression through ubiquitination of NLRP3,promoting ESCA cell proliferation.This suggests that CDC20 and NLRP3 may be potential diagnostic targets for ESCA.

Objective:To investigate the perfection and improvement of the execution of integrative medicine therapy in severe tetanus therapy, to successfully control tetanus severe spasms, autonomic dysfunction and prevent lethal side-effect of prolong and high-dosage sedative-muscle-relaxant therapy, resulted in significant reduction of mortality of tetanus.Methods:Symptoms, treatments and outcome of tetanus patients admitted to Peking University Third Hospital from 1965 to 2020 were reviewed. Patients were classified with Ablett classification. The cases of Ablett grade Ⅲ and Ⅳ were severe tetanus. The patients were divided into two groups according to whether they were treated together with traditional Chinese medicine (TCM) simultaneously during the standard tetanus treatment; the patients in the TCM group were divided into the tetanus TCM medication group and the non tetanus TCM medication group according to the medicine provided whether was in accord with the conventional tetanus TCM prescriptions. The mortality of each group was calculated. In addition, one survived and one deceased case with severe convulsion, autonomic nerve dysfunction (Ablett grade Ⅳ) were selected, combined with the treatment methods and curative effects, the types, use methods and outcomes of Chinese and Western medicine were analyzed.Results:The 46 tetanus cases were treated with Western medicine. Twenty-two of them, TCM were applied. Fifteen of the 22 cases took the TCM prescription which was accord with the conventional tetanus prescription. The mortality of the 46 cases was 21.7% (10/46). The number of non-TCM group was 24 cases, with mortality of 20.8% (5/24); 1 case was Ablett Ⅱ, 1 was Ablett Ⅲ and 3 were Ablett Ⅳ. The number of the TCM group was 22 cases, with mortality of 22.7% (5/22), 2 cases were Ablett Ⅲ, 3 were Ablett Ⅳ. The TCM prescription of these 5 deceased cases was not directed towards tetanus. The tetanus TCM medication group was 15 cases, with no mortality. Case analyses: case 1 was intubated because of severe spasms. Autonomic dysfunction occurred on the 8th day after admission. Esmolol with increasing the dosage of the sedatives and muscle relaxant, was not effective. Tetanus TCM was applied after 2 days of autonomic dysfunction happened. Autonomic dysfunction was then under controlled on the 2nd day post-TCM. She was recovery and discharged after 4 weeks. Case 2, also was intubated because of severe spasms. Autonomic dysfunction happened on the 3rd day after admission, and failed to be controlled by large-dose sedatives, muscle relaxant, and Esmolol. After 8 days of persistent autonomic dysfunction, tetanus TCM was applied and autonomic dysfunction was under controlled on the 2nd day post-TCM administration. Large dosage of muscle-relaxant was applied continuously. After 5 days' administration of TCM, the TCM was withdrew. One day after the withdrawal of TCM, respiratory and cardiac arrest happened because of the diffused bronchiole obstruction with pulmonary secretions loading.Conclusion:Based on the precise and real-time diagnosis of the state of the disease, integrative medicine therapy with an overall analysis tetanus TCM prescription, is the key of declining tetanus mortality.

Objective To understand the awareness level of iodine deficiency (ID) impairments and the attitude on edible iodized salt,and its consumption among doctors and nurses in cities,in order to provide scientific evidence for health education on iodine deficient disorders (IDD) in the future.Methods The questionnaire was self-designed,and spread through the web page of Wenjuanxing,an online server company,from May 6 to June 6,2017.At the end of the survey,a total of 481 valid questionnaires were reclaimed,in which ratio of gender was female 63.8％ (307/481),male 36.2％ (174/481).The data were analyzed by SPSS 22.0,including logistic regression analysis with backward according to the statistical significant level of P ＜ 0.05.Results Among doctors and nurses,90.4％ (435/481) knew ID impairments;72.8％ (350/481) answered intelligent disability as the most serious problem of ID;55.5％ (267/481)misunderstood that the areas in which they lived were not ID areas,although all cities surveyed were ID areas;41.0％ (197/481) of doctors and nurses misunderstood that coastal residents did not need to consume iodized salt.About the evaluation of iodine nutrition status of current population,15.6％ (75/481) of respondents judged as iodine excess.About consuming edible salt,76.3％ (367/481) selected iodized,9.6％ (46/481)non-iodized,and 14.1％ (68/481) both iodized and non-iodized.The results of logistic regression analysis showed the factors that prevents health care workers from choosing iodized salt were:"living in coastal areas","think him or her as iodine adequate","know that iodine deficiency can affect the development of children but still adhere to the consumption of non-iodized salt";the factors that promoted the choice of iodized salt for medical staff were "insist on buying iodized salt,and do not choose non-iodized salt",and 75.8％ (238/314)of them knew that intelligent disability as the most serious problem of ID.Conclusions Most doctors and nurses have high level of knowledge on ID and its control.But lack of information,as well as misunderstanding of "coastal areas iodine adequate" and worry about "excess iodine causes thyroid diseases and cancer",which would hinder the active consumption of iodized salt.Health education for them should be conducted through professional ways,stressing on the threaten of ID environment,sharing the information about national and local progress on control of IDD and iodized salt safety,and clarifying the relationship between iodine salt or iodine and thyroid cancer and nodules.

Objective To compare the clinical effects of combined anterolateral and posterolateral approach,lateral incision via double intermuscular spatia approach,and posterolateral transfibular approach in the treatment of fractures of anterolateral and posterolateral columns of tibial plateau.Methods A retrospective analysis was done of the 18 patients with fracture of anterolateral and posterolateral columns of tibial plateau who had been treated at our hospital from January 2012 to January 2015.They were 10 men and 8 women,aged from 28 to 58 years (mean,35.5 years).They were divided into 3 equal groups.Group A was treated with combined anterolateral and posterolateral approach,group B with lateral incision via double intermuscular spatia approach and group C with posterolateral transfibular approach.Operation time,surgical blood loss and complications were recorded.At the final follow-ups,Rasmussen score was used to evaluate the fracture reduction and Hospital for Special Surgery (HSS) knee score to assess functions of the involved knees.Results The 18 patients were followed up for 10 to 18 months (average,13.3 months).No such early complications as incision infection or deep vein thrombosis occurred.The operation time (89.5 min and 79.3 min,respectively) and surgical blood loss (151.7 mL and 207.8 mL,respectively) for groups A and B were obviously less than those for group C (102.5 min;260.2 mL);the incision length for group A (10.5 cm) was shorter than that for group B (17.4 cm) and for group C (16.3 cm);group C had more cases of excellent reduction (6) than groups A and B (4 for both).There were no obvious differenc es between groups A,B and C in the Rasmussen score (16.8,17.0 and 16.3) or HSS score (86.3,86.0 and 85.7).One case of delayed incision healing due to partial necrosis occurred in group B.At the final follow-ups in group C,the varus stress test showed 2 cases of laxation of degree Ⅱ and 2 cases of laxation of degree Ⅰ.Conclusions In the treatment of fractures of anterolateral and posterolateral columns of tibial plateau,all the 3 approaches can lead to good exposure,fine reduction,rigid fixation and satisfactory outcomes.Although the combined anterolateral and posterolateral approach and lateral incision via double intermuscular spatia approach can lead to similar exposure ranges and fixation effects,the latter is easier in operation while the former exposes the anterior and posterior spatia more fully,allowing the anterior and posterior plates to be better positioned.The posterolateral transfibular approach can lead to the largest exposure range and more precise reduction,but it has risks of damage to the lateral ligamentous structure,greater invasion,postoperative lateral instability and injury to the common peroneal nerve.

Objective:To evaluate the clinical efficacy of tendon-regulating manipulation plus kinesiotherapy in treating low back pain. Methods:Sixty patients were randomized into a treatment group and a control group by using the random number table, 30 cases in each group. The treatment group was intervened by tendon-regulating manipulation plus kinesiotherapy, while the control group was by the tendon-regulating manipulation alone. The lumbar lordosis was measured by X-ray (side view), the pain was evaluated by analgesy meter, the lumbar range of motion was by using goniometer, and the function was judged by Oswestry disability index (ODI) before and after treatment, and the therapeutic efficacy was also observed. Results:After treatment, the pain level was significantly reduced, lumbar lordosis was significantly increased, the lumbar range of motion was markedly improved, and the ODI score significantly dropped (allP<0.05) in both groups; the improvement of each item in the treatment group was more significant than that in the control group (allP<0.05). The total effective rate was 90.0% in the treatment group versus 63.3% in the control group, and the difference was statistically significant (P<0.05). Conclusion:In the treatment of low back pain, tendon-regulating manipulation plus kinesiotherapy can mitigate topical pain, improve the motion of low back, enhance the quality of life, and produce a more significant therapeutic efficacy compared to tendon-regulating manipulation alone.

Objective To explore the risk factors of the occurence and 28-day death of acute respiratory distress syndrome (ARDS) in intensive care unit (ICU). Methods A prospective multicentral cohort study was conducted. The patients from five ICUs of grade A tertiary hospitals in Beijing from July 2009 to March 2014, including sepsis,septic shock,trauma,pneumonia,aspiration,massive blood transfusion,bacteremia and pulmonary contusion,were enrolled. Researchers in each center reported the records with uniform tables,which included demographic,systemic conditions,the primary disease,and the severity within 24 hours,past history and so on. According to the admission diagnosis in ICU,these patients were divided into ARDS group and other severe disease control group. The risk factors of occurence and prognosis of ARDS were analyzed by univariate analysis,multivariate logistic regression and multivariate COX regression analysis. Kaplan-Meier method was applied to draw the 28-day survival curves of the two groups. Results There were 343 critical patients included in this prospective multicenter cohort study,of which 163 patients who developed ARDS were considered as ARDS group(2 case lost to follow-up, and 49 died)and 180 patients who did not developed ARDS regarded as severe control group(1 case lost to follow-up, and 34 died). The 28-day mortality of ARDS group was significantly higher than that of severe control group〔30.43%(49/161)vs. 18.99%(34/179),χ2=6.013,P=0.014〕. Multivariate logistic analysis showed that aspiration〔odds ratio(OR)=6.390,95% confidence interval(95%CI)=2.046-19.953,P=0.001〕,history of alcohol (OR=4.854,95%CI=1.730-13.617,P=0.003),sepsis(OR=2.859,95%CI=1.507-5.425,P=0.001), pneumonia(OR=2.822,95%CI=1.640-4.855,P<0.001),acute physiology and chronic health evaluation Ⅱ(APACHEⅡ)score(OR=1.050,95%CI=1.007-1.094,P=0.022)were significantly associated with increased risk of ARDS occurence. When respiratory rate>30 beats/min(OR=3.305,95%CI=1.910-5.721,P<0.001), heart rate>100 beats/min(OR=2.101,95%CI=1.048-4.213,P=0.037)happened in critically ill patients, it highly suggested ARDS would happen. The proportion of the patients whose serum creatinine>176.8 μmol/L in ARDS group was lower than that in control group(OR=0.387,95%CI=0.205-0.733,P=0.004). Multivariate COX regression analysis showed that old age and septic shock were significantly associated with the increased risk of in 28-day death of ARDS〔advanced age:hazard ratio(HR)=1.040,95%CI=1.018-1.064,P<0.001;septic shock:HR=3.209,95%CI=1.676-6.146,P<0.001〕. Kaplan-Meier showed that the survival patients in ARDS group was significantly lower than those in severe control group(χ2=7.032,P=0.008). Conclusions Among critical ill patients,aspiration,history of alcohol,sepsis,pneumonia,increased APACHEⅡ score were the risk factors of ARDS development. Respiratory rate>30 beats/min and heart rate>100 beats/min could predict the occurrence of ARDS in critical patients. Old age and septic shock were the risk factors of 28-day death of ARDS.

Objective To investigate the variation of procalcitonin(PCT) in blood and tissue level of acute pancreatitis rats and probe its significant. Methods One hundred and two male Wistar rats were randomly divided into control group ( n = 6 ), lipopolysaccharide group ( LPS, n = 24 ), acute edematous pancreatitis (AEP) group ( n = 24), acute necrotizing pancreatitis (ANP) group ( n = 24), AN P + LPS group ( n = 24). Subcutaneous injection of cerulein was used for AEP induction, while ANP model was induced by retrograde injection of sodium taurocholate into the biliary and pancreatic duct. The rats were sacrificed at 3,6, 18 and 24 hours after model induction. Pancreatic tissue was harvested and the pathological scores were assessed. Levels of PCT in serum, liver, lung, spleen, pancreas, small intestine, large intestine tissue was harvested and tissue levels of PCT were determined. Results AEP and ANP models were established successfully. At 6 h, the serum levels of PCT in control group, LPS group, AEP group, ANP group and ANP +LPS group were (0.0144 ±0.0082) ng/ml, (0. 1722 ±0.0449) ng/ml,(0.4751 ±0.0572) ng/ml, (0.7070 ±0. 1040) ng/ml and ( 1. 1960 ±0.8644) ng/ml, respectively; and the difference was statistically significant (P < 0.05 ). PCT could be detected in liver, lung, spleen, pancreas, small intestine and large intestine tissue of normal rats. PCT levels in liver and pancreas of ANP group were not statistically different, but the PCT levels in lung, spleen, and large intestine tissue significantly decreased, and the corresponding values were (5.63 ±0.62) ng/ml vs. (6.85 ±0.46) mg/ml, (4.73 ±1.27) mg/ml vs. (6.88 ±0.37) ng/ml, (1.08 ±0.52) ng/ml vs. (4.12 ± 1.02) ng/ml (P <0.01 ). However, the PCT levels in small intestine significantly increased, which were (2.51 ±0.90) ng/ml vs (0.98 ±0. 12) ng/ml (P<0. 01). Conclusions Serum PCT level was associated with the severity of AP and infection; the changes of PCT levels in different tissues may be related with the changes of organ's function.