The Effect of Shenqi Jianxin Formula （参芪健心方） on Cardiomyocyte Pyroptosis in Chronic Heart Failure Model Rats Based on the NLRP3/Caspase-1 Signaling Pathway / 中医杂志

ObjectiveTo investigate the possible mechanism of Shenqi Jianxin Formula （参芪健心方） in the treatment of chronic heart failure （CHF） from the perspective of pyroptosis. MethodsFifty-two rats were randomly divided into sham operation group （n=8） and modeling group （n=44）. In the modeling group， the anterior descending branch of the left coronary artery was ligated to construct CHF rat model. Forty successfully-modelled rats were randomly divided into model group， Entresto group， Shenqi Jianxin Formula group， MCC950 group and the combination group （Shenqi Jianxin Formula plus MCC950）， with 8 rats in each group. In Shenqi Jianxin Formula group， 7.4 g/（kg·d） of Shenqi Jianxin Formula was given by gavage， while in Entresto group， 68 mg/（kg·d） of Entresto suspension was given by gavage； in MCC950 group， MCC950 was injected intraperitoneally with 10 mg/kg once every other day， and in the combination group， 7.4 g/（kg·d） of Shenqi Jianxin Formula was given by gavage， and MCC950 was injected intraperitoneally with 10 mg/kg once every other day； 10 ml/（kg·d） of saline was given by gavage in the sham operation group and the model group. After 3 weeks of continuous intervention， serum brain B-type natriuretic peptide （BNP）， creatine kinase isoenzyme MB （CK-MB）， interleukin 1β （IL-1β）， and interleukin 18 （IL-18） levels were detected by ELISA； HE staining and MASSON staining were used to observe pathological changes in rat myocardium. Except for the Entresto group， western blot technique was used to detect the expression of NOD-like receptor protein 3 （NLRP3）， caspase-1， and apoptosis-associated speck-like protein possessing a caspase-recruiting domain （ASC）； RT-PCR was used to detect the expression of NLRP3 and caspase-1 mRNA. ResultsCompared with the sham operation group， HE staining of rats in the model group showed obvious myocardial injury， while MASSON staining showed increased area of collagen fibrosis， and serum BNP， CK-MB， IL-1β， IL-18， myocardial tissue NLRP3， caspase-1， ASC protein expression and NLRP3， caspase-1 mRNA expression were all elevated （P＜0.05）. Compared with those in the model group， cardiomyocyte injury of rats and collagen fibrosis area were reduced， and serum BNP， CK-MB， IL-1β， and IL-18 contents were all reduced in Shenqi Jianxin Formula group， Entresto group， MCC950 group， and the combination group； except for Entresto group， myocardial tissue NLRP3， caspase-1， ASC protein expression and NLRP3， caspase-1 mRNA expression were reduced in the remaining three medication group （P＜0.05）. Compared with Shenqi Jianxin Formula group， the MCC950 group and the combination group showed decreased serum IL-1β and IL-18 content， collagen fibrosis area， myocardial tissue NLPR3， caspase-1 protein expression， and caspase-1 mRNA expression， and decreased ASC and NLRP3 mRNA expression was shown in the combination group （P＜0.05）. Compared with MCC950 group， collagen fibrosis area was reduced， and serum IL-18 content， NLRP3， caspase-1 mRNA expression were reduced in the combination group （P＜0.05）. ConclusionShenqi Jianxin Formula can effectively improve the myocardial injury and heart failure in rats with CHF， and its mechanism may be related to the inhibition of cardiomyocyte pyroptosis through NLPR3/Caspase-1 pathway to reduce the level of intramyocardial inflammation. The combined use of MCC950 with Shenqi Jianxin Formula could more effectively inhibite myocardial pyroptosis， with better therapeutic result than single use of each part.

AAZ2 induces mitochondrial-dependent apoptosis by targeting PDK1 in gastric cancer / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

Drastic surges in intracellular reactive oxygen species (ROS) induce cell apoptosis, while most chemotherapy drugs lead to the accumulation of ROS. Here, we constructed an organic compound, arsenical N-‍(4-(1,3,2-dithiarsinan-2-yl)phenyl)acrylamide (AAZ2), which could prompt the ROS to trigger mitochondrial-dependent apoptosis in gastric cancer (GC). Mechanistically, by targeting pyruvate dehydrogenase kinase 1 (PDK1), AAZ2 caused metabolism alteration and the imbalance of redox homeostasis, followed by the inhibition of phosphoinositide-3-kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) pathway and leading to the activation of B-cell lymphoma 2 (Bcl2)/Bcl2-associated X (Bax)/caspase-9 (Cas9)/Cas3 cascades. Importantly, our in vivo data demonstrated that AAZ2 could inhibit the growth of GC xenograft. Overall, our data suggested that AAZ2 could contribute to metabolic abnormalities, leading to mitochondrial-dependent apoptosis by targeting PDK1 in GC.

Current status of pediatric respiratory therapist / 中国小儿急救医学

Respiratory therapist is a new profession in medicine, who works therapeutically with people suffering from pulmonary disease.Their timely treatments of patients with cardiopulmonary insufficiency can significantly reduce mortality in pediatric intensive care units.This review focused on the responsibilities of respiratory therapists, the importance of respiratory support therapy in children, and the most updated development in China as well as the problems to be solved.

Analysis of clinical characteristics of early death in adult patients with hemophagocytic syndrome / 白血病·淋巴瘤

Objective:To explore the clinical characteristics of early death in adult patients with hemophagocytic syndrome (HPS).Methods:The clinical data of 53 adult HPS patients in Xianning Central Hospital, Huangshi Central Hospital and Tongji Hospital Affiliated to Tongji Medical College of Huazhong University of Science and Technology from September 2016 to November 2021 were retrospectively analyzed, and the patients were grouped according to whether they died within 28 d after diagnosis. The clinical characteristics of the two groups were compared. A multivariate analysis of patients' death within 28 d was performed using logistic regression.Results:In 53 adult HPS patients, the mortality rate within 28 d was 28.3% (15/53). The survival time of patients was related to white blood cell count ( r = 0.324, P = 0.018), total bilirubin level ( r = -0.280, P = 0.042) and albumin level ( r = 0.281, P = 0.042), but there was no linear causality (all P > 0.05). When compared between the death within 28 d group and the non-death within 28 d group, the differences in patients' age, platelet count, albumin level, creatine kinase isoenzyme level, triacylglycerol level, ferritin level, and central nervous system involvement were statistically significant (all P < 0.05). Multivariate logistic regression analysis showed that platelet count <30×10 9/L, albumin <30 g/L, central nervous system involvement, and ferritin ≥10 000 ng/ml were independent risk factors for patients' death within 28 d (all P < 0.05). Conclusions:In adult HPS patients, assessing the risk of early death based on ferritin level, platelet count, albumin level, and neurological symptoms, actively correcting internal environmental disturbances, and enhancing organ support therapy can contribute to survival benefit.

Mechanism of large-conductance calcium-activated potassium channel involved in inflammatory response in sepsis / 中华危重病急救医学

OBJECTIVE@#To explore the mechanisms of large-conductance calcium-activated potassium channel (BKCa) involved in inflammatory response in sepsis.@*METHODS@#The serum levels of BKCa were measured by enzyme-linked immunosorbent assay (ELISA) in patients with sepsis (28 cases), patients with common infection (25 cases) and healthy people (25 cases). The relationship between levels of BKCa and acute physiology and chronic health evaluation II (APACHE II) were analyzed. Cultured RAW 264.7 cells were stimulated by lipopolysaccharide (LPS). In some experiments, a cell model of sepsis was constructed using Nigericin as the second stimulus signal. The mRNA and protein expressions of BKCa in RAW 264.7 cells stimulated with LPS (0, 50, 100, 1 000 μg/L) were measured by real-time fluorescence quantitative polymerase chain reaction (RT-qPCR) and Western blotting. RAW 264.7 cells were transfected with small interfering RNA of BKCa (siRNA-BKCa), and the levels of caspase-1 precursor (pro-caspase-1), interleukin-1β precursor (pro-IL-1β) in cell, and the levels of caspase-1 p20, IL-1β p17 of cell culture medium, and NOD-like receptor protein 3 (NLRP3), nuclear factor-κB (NF-κB) were measured by Western blotting. The apoptosis were detected by staining with propidium iodide (PI), the release rate of lactate dehydrogenase (LDH) were measured, and the expression of apoptotic protein Gasdermin D (GSDMD) was measured by Western blotting to evaluate the effect of silencing BKCa on cell pyrosis.@*RESULTS@#The level of serum BKCa in patients with sepsis was significantly higher than that in patients with common infection and health peoples (ng/L: 165.2±25.9 vs. 102.5±25.9, 98.8±20.0, both P < 0.05). In addition, the level of serum BKCa in patients with sepsis was significantly positively correlated with APACHE II score (r = 0.453, P = 0.013). LPS could construct a sepsis cell model by which LPS could promote BKCa expression in mRNA and protein with a concentration-dependent manner. The mRNA and protein expressions of BKCa in the cells stimulated by 1 000 μg/L LPS were significantly higher than that in the blank group (0 μg/L) [BKCa mRNA (2-ΔΔCt): 3.00±0.36 vs. 1.00±0.16, BKCa/β-actin: 1.30±0.16 vs. 0.37±0.09, both P < 0.05]. Compared with the control group, the ratios of caspase-1 p20/pro-caspase-1 and IL-1β p17/pro-IL-1β in the model group were significantly increased (caspase-1 p20/pro-caspase-1: 0.83±0.12 vs. 0.27±0.05, IL-1β p17/pro-IL-1β: 0.77±0.12 vs. 0.23±0.12, both P < 0.05), however, transfection of siRNA-BKCa induced the decrease both of them (caspase-1 p20/pro-capase-1: 0.23±0.12 vs. 0.83±0.12, IL-1β p17/pro-IL-1β: 0.13±0.05 vs. 0.77±0.12, both P < 0.05). Compared with the control group, the number of apoptotic cells, LDH release rate and GSDMD expression in the model group were significantly increased [LDH release rate: (30.60±8.40)% vs. (15.20±7.10)%, GSDMD-N/GSDMD-FL: 2.10±0.16 vs. 1.00±0.16, both P < 0.05], however, transfection of siRNA-BKCa induced the decrease both of them [LDH release rate: (15.60±7.30)% vs. (30.60±8.40)%, GSDMD-N/GSDMD-FL: 1.13±0.17 vs. 2.10±0.16, both P < 0.05]. The mRNA and protein expressions of NLRP3 in sepsis cells were significantly higher than those in the control group [NLRP3 mRNA (2-ΔΔCt): 2.06±0.17 vs. 1.00±0.24, NLRP3/GAPDH: 0.46±0.05 vs. 0.15±0.04, both P < 0.05]. However, the expression of NLRP3 after siRNA-BKCa transfection was significantly lower than that in model group [NLRP3 mRNA (2-ΔΔCt): 1.57±0.09 vs. 2.06±0.17, NLRP3/GAPDH: 0.19±0.02 vs. 0.46±0.05, both P < 0.05]. Compared with the control group, the NF-κB p65 nuclear transfer of sepsis cell were significantly increased (NF-κB p65/Histone: 0.73±0.12 vs. 0.23±0.09, P < 0.05). However, the NF-κB p65 expression in the nucleus were decreased after siRNA-BKCa transfection (NF-κB p65/Histone: 0.20±0.03 vs. 0.73±0.12, P < 0.05).@*CONCLUSIONS@#BKCa is involved in the pathogenesis of sepsis, and its possible mechanism is to activate NF-κB/NLRP3/caspase-1 signaling pathway to induce inflammatory factor production and cell death.

Development of mortality prediction model for critically ill patients based on multidimensional and dynamic clinical characteristics / 中华危重病急救医学

OBJECTIVE@#To develop a mortality prediction model for critically ill patients based on multidimensional and dynamic clinical data collected by the hospital information system (HIS) using random forest algorithm, and to compare the prediction efficiency of the model with acute physiology and chronic health evaluation II (APACHE II) model.@*METHODS@#The clinical data of 10 925 critically ill patients aged over 14 years old admitted to the Third Xiangya Hospital of Central South University from January 2014 to June 2020 were extracted from the HIS system, and APACHE II scores of the critically ill patients were extracted. Expected mortality of patients was calculated according to the death risk calculation formula of APACHE II scoring system. A total of 689 samples with APACHE II score records were used as the test set, and the other 10 236 samples were used to establish the random forest model, of which 10% (n = 1 024) were randomly selected as the validation set and 90% (n = 9 212) were selected as the training set. According to the time series of 3 days before the end of critical illness, the clinical characteristics of patients such as general information, vital signs data, biochemical test results and intravenous drug doses were selected to develope a random forest model for predicting the mortality of critically ill patients. Using the APACHE II model as a reference, receiver operator characteristic curve (ROC curve) was drawn, and the discrimination performance of the model was evaluated through the area under the ROC curve (AUROC). According to the precision and recall, Precision-Recall curve (PR curve) was drawn, and the calibration performance of the model was evaluated through the area under the PR curve (AUPRC). Calibration curve was drawn, and the consistency between the predicted event occurrence probability of the model and the actual occurrence probability was evaluated through the calibration index Brier score.@*RESULTS@#Among the 10 925 patients, there were 7 797 males (71.4%) and 3 128 females (28.6%). The average age was (58.9±16.3) years old. The median length of hospital stay was 12 (7, 20) days. Most patients (n = 8 538, 78.2%) were admitted to intensive care unit (ICU), and the median length of ICU stay was 66 (13, 151) hours. The hospitalized mortality was 19.0% (2 077/10 925). Compared with the survival group (n = 8 848), the patients in the death group (n = 2 077) were older (years old: 60.1±16.5 vs. 58.5±16.4, P < 0.01), the ratio of ICU admission was higher [82.8% (1 719/2 077) vs. 77.1% (6 819/8 848), P < 0.01], and the proportion of patients with hypertension, diabetes and stroke history was also higher [44.7% (928/2 077) vs. 36.3% (3 212/8 848), 20.0% (415/2 077) vs. 16.9% (1 495/8 848), 15.5% (322/2 077) vs. 10.0% (885/8 848), all P < 0.01]. In the test set data, the prediction value of random forest model for the risk of death during hospitalization of critically ill patients was greater than that of APACHE II model, which showed by that the AUROC and AUPRC of random forest model were higher than those of APACHE II model [AUROC: 0.856 (95% confidence interval was 0.812-0.896) vs. 0.783 (95% confidence interval was 0.737-0.826), AUPRC: 0.650 (95% confidence interval was 0.604-0.762) vs. 0.524 (95% confidence interval was 0.439-0.609)], and Brier score was lower than that of APACHE II model [0.104 (95% confidence interval was 0.085-0.113) vs. 0.124 (95% confidence interval was 0.107-0.141)].@*CONCLUSIONS@#The random forest model based on multidimensional dynamic characteristics has great application value in predicting hospital mortality risk for critically ill patients, and it is superior to the traditional APACHE II scoring system.

Short-chain fatty acids ameliorate spinal cord injury recovery by regulating the balance of regulatory T cells and effector IL-17+ γδ T cells / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

Spinal cord injury (SCI) causes motor, sensory, and autonomic dysfunctions. The gut microbiome has an important role in SCI, while short-chain fatty acids (SCFAs) are one of the main bioactive mediators of microbiota. In the present study, we explored the effects of oral administration of exogenous SCFAs on the recovery of locomotor function and tissue repair in SCI. Allen's method was utilized to establish an SCI model in Sprague-Dawley (SD) rats. The animals received water containing a mixture of 150 mmol/L SCFAs after SCI. After 21 d of treatment, the Basso, Beattie, and Bresnahan (BBB) score increased, the regularity index improved, and the base of support (BOS) value declined. Spinal cord tissue inflammatory infiltration was alleviated, the spinal cord necrosis cavity was reduced, and the numbers of motor neurons and Nissl bodies were elevated. Enzyme-linked immunosorbent assay (ELISA), real-time quantitative polymerase chain reaction (qPCR), and immunohistochemistry assay revealed that the expression of interleukin (IL)‍-10 increased and that of IL-17 decreased in the spinal cord. SCFAs promoted gut homeostasis, induced intestinal T cells to shift toward an anti-inflammatory phenotype, and promoted regulatory T (Treg) cells to secrete IL-10, affecting Treg cells and IL-17+ γδ T cells in the spinal cord. Furthermore, we observed that Treg cells migrated from the gut to the spinal cord region after SCI. The above findings confirm that SCFAs can regulate Treg cells in the gut and affect the balance of Treg and IL-17+ γδ T cells in the spinal cord, which inhibits the inflammatory response and promotes the motor function in SCI rats. Our findings suggest that there is a relationship among gut, spinal cord, and immune cells, and the "gut-spinal cord-immune" axis may be one of the mechanisms regulating neural repair after SCI.

Bone turnover markers, hip bone geometry parameters and metabolic syndrome in community overweight postmenopausal women / 中华内分泌代谢杂志

Objective:To explore the changes of bone turnover markers and geometric parameters of hip bone in overweight postmenopausal women with metabolic syndrome(MS), as well as the influence of MS components. To analyze the association of these factors with the risk of fracture.Methods:A total of 505 overweight postmenopausal female patients who underwent health check-up in Lianhu Community Service Center, Danyang City, Jiangsu Province from January to December 2017 were selected. According to the MS diagnostic criteria of the International Diabetes Federation(2009), the patients were divided into MS group( n=331)and non-MS group( n=174). Blood samples were collected to determine the level of procollagen type 1 N-terminal propeptide(P1NP)and carboxy-terminal cross-linked telopeptide of type 1 collagen(CTX). Bone mineral density and hip bone geometry parameters were tested with dual-energy X-ray absorptiometry and hip structural analysis software. Results:The incidence of osteoporotic fracture and hip fracture in MS group was significantly higher than that in non-MS group(21.1% vs 13.8%, 4.8% vs 1. 1%, P<0.05). However, the bone mineral density of lumbar vertebra 1-4, femoral neck, and total hip in MS group was significantly higher than that in non-MS group, which remained after adjusting for age( P<0.05), but the difference disappeared after further adjustment for body mass index( P>0.05). The P1NP, CTX, femur strength index(FSI), section modulus(SM), and cross-sectional area(CSA)of MS group were significantly lower than those of non-MS group, the buckling ration(BR)was significantly higher than that in non-MS group, and the differences were still statistically significant after adjusting for age and body mass index( P<0.05). There was no significant difference in bone mineral density of lumbar vertebra 1-4, femoral neck, total hip, P1NP, and CTX between fracture group and non-fracture group in patients with MS. But FSI, SM, cross-sectional moment of inertia(CSMI), and CSA were significantly lower, BR was significantly higher( P<0.05) and femur strength decreased in patients with fracture. Regression analysis showed that high BR was an independent risk factor for fracture risk, while high FSI, SM, CSMI, and CSA were protective factors. Multivariate linear regression analysis showed that wasit circumference, diastolic blood pressure, and fasting plasma glucose were the main MS components affecting bone mineral density, bone turnover indexes, and hip bone geometry parameters. Conclusions:Overweight postmenopausal MS patients had decreased bone turnover rate, femoral strength, and relatively poor bone quality. Hip bone geometry parameters can be used as one of the methods to assess fracture risk in MS patients. Waist circumference, diastolic blood pressure, and fasting blood glucose are the important MS components affecting bone mass and bone quality.

Interpretation of the international expert consensus guideline on exercise management for older adults / 中华老年医学杂志

Ageing and a sedentary lifestyle are associated with declines in muscle function and cardiopulmonary fitness in older adults and may eventually lead to reduced capabilities to conduct daily activities and independent living.Exercise plays an important role in maintaining physical function and mental health, preventing and treating chronic diseases, reducing mortality, and improving the quality of life in older people.In 2021, the International Conference of Frailty and Sarcopenia Research(ICFSR)proposed international expert consensus guidelines on exercise recommendations for older people.It mainly introduces two aging phenotypes and six recommended exercise modalities and discusses the effects of exercise on maintaining physical health and preventing common chronic diseases and geriatric syndromes.It aims to provide suggestions for older adults to maintain physical fitness and prevent disease progression and disability via exercise.We intend to interpret the important contents of the guidelines to provide a reference for exercise research and practical applications in the elderly in China.

Anti-neurexin-3α antibody-associated encephalitis with parkinsonism as the main manifestation: a case report / 中华神经科杂志

Anti-neurexin-3α antibody-associated encephalitis is rare in clinical practice. It often has a history of pre-infection. It is characterized by abnormal mental behavior, seizures, decreased consciousness, cognitive and sleep disorders, movement disorder, central hypoventilation and autonomic nervous dysfunction. Among them, dyskinesias are mainly involuntary movements of the mouth, face and limbs, dystonia, myoclonic seizures and other manifestations of increased movement. Parkinson′s symptoms manifested as decreased movement are rarely reported. A encephalitis patient with positive anti-neurexin-3α antibody is reported, who is a young female, mainly with parkinsonism such as slow movement, unsteady walking, difficulty in starting and turning around, and inability to hold things in both upper limbs, accompanied by abnormal mental behavior and cognitive dysfunction. After treatment with methylprednisolone and intravenous immunoglobulin, the prognosis is good.

A multi-center survey of medical staffs′ cognition and management of prolonged mechanical ventilation in pediatric intensive care unit / 中国小儿急救医学

Objective:To investigate the status of cognition and clinical management of prolonged mechanical ventilation(PMV) among medical staffs in pediatric intensive care unit(PICU) in China, and in order to improve the awareness of PICU medical staffs on PMV and standardize the management of PMV.Methods:The cross-sectional study was conducted with doctors and nurses in PICUs of the collaborative group as the survey objects from July 12 to September 12, 2020.The questionnaire was issued, collected and checked by the Children′s Hospital of Fudan University.Results:(1) PMV related settings: Nine out of eleven hospitals had established PMV multidisciplinary teams, respiratory techniques such as diaphragm ultrasound and airway peak flow monitoring could be respectively executed in 72.7% and 36.4% of PICU.Pulmonary rehabilitation techniques such as airway clearance techniques, induced spirometer exercise, external diaphragm pacemaker stimulation, transfer bed exercise, balloon blowing, hyperbaric oxygen therapy could be respectively executed in 100.0%, 9.1%, 9.1%, 9.1%, 27.3% and 27.3% of PICU, respectively.(2) The cognitive status quo of children′s PMV: The most medical staffs agreed with the view that PMV referred to the children′s continuous mechanical ventilation for more than two weeks.Sixty percent of medical staffs believed that children with PMV had basic central nervous system diseases, and 62.7% of medical staffs believed that the most common causes of difficulty in PMV weaning was abnormal brain function.(3) The cognitive status quo of the children′s PMV management in PICU: Respondents believed that the most commonly used mechanical ventilation mode was synchronized intermittent mandatory ventilation+ pressure support ventilation in children′s PMV during stable disease.Ninety-two percent of medical staffs performed the spontaneous breathing test when weaning.And 58.7% of the respondents agreed to perform tracheotomy for the children during 3 to 4 weeks of mechanical ventilation.More than half of medical staffs would execute diaphragm function assessment, bedside rehabilitation training, nutritional assessment, analgesia and sedation assessment for children with PMV.(4) The cognitive status quo of the children′s PMV management of transition from hospital to family: 54.5% of PICU provided family care training to the family members before the children were discharged from the hospital.One center established the PMV specialized outpatient clinic.45.5% of PICU would follow up these discharged children one month later.Conclusion:At present, PICU medical staffs have different awareness of children′s PMV related problems in China.And children′s PMV lacks a systematic plan regarding diagnosis, treatment and management.

Analysis of clinical phenotypes and ATP7B gene variants in 75 children patients with Wilson' s disease / 中华医学遗传学杂志

OBJECTIVE@#To analyze the clinical phenotypes and ATP7B gene variants among children patients with Wilson' s disease from Northwestern China.@*METHODS@#The clinical features and variants of the ATP7B gene among 75 children with hepatic Wilson' s disease were retrospectively analyzed.@*RESULTS@#Among the 75 cases, 4 were presymptomatic, 59 had isolated transaminase elevation, 12 had acute and/or chronic liver diseases. Nine children were found to harbor homozygous variants, 64 harbored compound heterozygous variants, and two only had heterozygous variants of the ATP7B gene. In total 49 variants were detected, with common variants including c.2333G>T (p.Arg778Leu), c.2621C>T (p.Ala874Val) and c.2975C>T (Pro992Leu), which yielded allelic frequencies of 28.7%, 12.7% and 9.3%, respectively. Six novel variants were detected, which included c.1908dupC (p.Asn637Glnfs*118), c.4179_4180insC (p.Pro1394Profs*15), c.1604A>G (p.Glu535Gly), c.2278C>T (p.Pro760Ser), c.3008C>A (p.Ala1003Glu) and c.3532A>C (p.Thr1178Pro). Except for c.1604A>G (p.Glu535Gly), the remainder five were all predicted to be likely pathogenic. No significant correlation was found between genotype and phenotype among the patients.@*CONCLUSION@#The common mutation types of the ATP7B gene among patients with hepatic Wilson disease in Northwestern China are c.2333G>T (p.Arg778Leu), c.2621C>T (p.Ala874Val) and c.2975C>T (p.Pro992Leu), there is no significant correlation between their genotypes and phenotypes.

Research progress on rodent frailty models / 中华老年医学杂志

Frailty is a geriatric syndrome characterized by declines in multisystem functions, decreased functional reserve, and increased vulnerability to adverse health events, and affects the quality of life in older adults.However, the underlying mechanisms of frailty are still unclear.Rodents share homology with humans and are commonly used as animal models to study human diseases.Rodent frailty models can promote frailty research and intervention in humans.We reviewed research progress on rodent frailty models in this article.

Dose effect of fluence-smoothing on intensity modulated planning after rectal cancer surgery / 中国辐射卫生

Objective To compare the dosimetric differences of four fluence smoothing (FS) levels of the Monaco system in intensity-modulated radiation therapy (IMRT) after rectal cancer surgery, and to provide a reference for FS selection in clinical practice. Methods A total of 15 postoperative patients with rectal cancer admitted in 2020 were selected. Under the same optimal conditions, FS was set to Off, Low, Medium, and High for IMRT planning. The data were analyzed by SPSS 20.0 software. The dosimetric parameters of planning target volume and organs at risk (OARs), the number of Segments, the number of monitor units (MUs), the estimated total delivery time (ETDT), and the gamma pass rate were compared between the four FS levels. Results The four FS levels resulted in clinically acceptable dosimetric parameters of the planning target volume and OARs, and there was no significant difference in dose distribution between FS levels. From FS-Off to FS-High, number of Segments, number of Mus, and ETDT decreased by 15.2%, 11.8%, and 6.7%, respectively, whereas gamma pass rate increased by 1.6%. Conclusion The IMRT plans at four FS levels can meet the clinical requirements. Considering the planning quality and execution efficiency, FS-High is recommended for postoperative IMRT of patients with rectal cancer.

Investigation of radiation protection status in non-medical radiation institutions in Fujian Province, China / 中国辐射卫生

@#<b>Objective</b> To investigate the number and categorical distribution of non-medical radiation institutions in Fujian Province, China, and to explore the current situation of radiation occupational hazards prevention and control and the occupational health management of radiation workers in employing units. <b>Methods</b> The industrial enterprises engaged in the application of nuclear technology in our province were investigated, and different types of employing units were selected to monitor the radioactivity level in the workplace. <b>Results</b> A total of 377 non-medical radiation institutions were reported in the province, with a total of 5221 radiation workers (except luggage detector units); 1246 radiation workers held radiation worker certificates, accounting for 23.87%; 5103 radiation workers carried out personal dose monitoring, accounting for 97.74%; 5061 radiation workers participated in radiation protection knowledge training, accounting for 96.94%; a total of 4895 (93.76%)radiation workers received physical examination. <b>Conclusion</b> Health supervision authorities in Fujian Province should strengthen the supervision of non-medical radiation institutions, further improve the level of occupational health management, and protect the health rights and interests of radiation workers to the maximum extent.

Study on determination of 2-thioxothiazolidine-4-carboxylic Acid in urine by high performance liquid chromatography / 中华劳动卫生职业病杂志

Objective: To establish a high performance liquid chromatography method for the determination of 2-thioxothiazolidine-4-carboxylic acid (TTCA) in urine. Methods: After acidification with hydrochloric acid, TTCA in urine was first extracted by ethyl acetate with excessive sodium chloride, then gradient separated by a symmetry C18 column and then detected by a diode array detector. The quantification was based on a working curve of external standard method. Results: The linear relationship of TTCA in urine was good in the range of 0.03-10.00 mg/L, and the correlation coefficient was 0.9999. The detection limit and minimum quantitative concentration of TTCA in urine were 0.008 mg/L and 0.027 mg/L. The intra-assay precision of the method was 0.9%-1.4%, the inter-assay precision was 1.3%-3.5%, and the average recovery was 85.0%-92.7% while the concentrations of TTCA in urine was 0.8, 2.0 and 8.0 mg/L, respectively (n=6) . Conclusion: The gradient elution high performance liquid chromatography method has simple operation and high sensitivity, and it is suitable for the determination of TTCA on a low level in urine for occupational workers exposure to carbon disulfide.

Clinical characteristics of Wilson's disease with onset of acute liver failure in 19 children / 中华儿科杂志

Objective: To analyze the clinical characteristics of Wilson's disease (WD) with onset of acute liver failure (ALF) in children. Methods: Clinical data of 19 children diagnosed with WD presented with ALF in Xi'an Children's Hospital from January 2016 to April 2021 were retrospectively analyzed, including general condition, clinical manifestation, laboratory examination, and gene detection. The children were divided into the death group and survival group according to the clinical outcome. The children who had hepatic WD with non-ALF onset during the same period were selected as the control. The general conditions and laboratory indexes were compared between death group and survival group, ALF group and non-ALF group. T-test, Mann Whitney U test or χ2 test were used to compare the differences between the two groups. Results: Of the 19 WD children with ALF onset, 10 were females and 9 were males. The age of admission was (10.1±2.6) years and time to onset of first visit was 9 (4, 15) days. Among the WD children with ALF onset, 4 children were lost to follow-up, 5 cases death (death group) and 10 cases survived (survival group). The ceruloplasmin in the death group was higher than that in the survival group (0.078 (0.055, 0.105) vs. 0.033 (0.027, 0.058) g/L, Z=-2.33, P=0.020). There were 95 children who had hepatic WD with non-ALF onset. The WD patients with ALF onset were older at admission (9.9 (8.0, 11.1) vs. 5.4 (3.7, 6.9) years, Z=-5.25, P<0.001), had higher ceruloplasmin (0.060 (0.030, 0.078) vs. 0.024 (0.006, 0.060) g/L, Z=-3.11, P=0.002), 24 h urinary copper (674 (205, 1 803) vs. 149 (108, 206) μg, Z=-4.25, P<0.001), and positive rate of K-F ring [17/19 vs. 7%(7/95), χ2=50.17, P<0.001] while shorter onset time at initial visit (0.3 (0.1, 0.5) vs. 1.0 (0.7, 6.0) months, Z=-4.28, P<0.001). There was no gender difference between the two groups [9/19 vs. 61%(58/95), χ2=1.22, P=0.269]. Of the 19 WD children with ALF onset, 13 had the ATP7B gene tested, and 15 reported variants were detected. The main variations were c.2333G>T (p. Arg778Leu), c.2621C>T (p. Ala874Val) and c.2975C>T (p. Pro992Leu). The allele frequencies were 6/26(23%), 4/26(15%) and 3/26(12%), respectively. Conclusions: Children of WD onset with ALF are school-aged and above. They have an acute onset, a short course of the disease, and poor prognosis. The positive rate of K-F ring, ceruloplasmin and urinary copper are higher than those of the hepatic WD children with non-ALF onset.

Repair impact of vibration exercise with different frequencies on articular cartilage of rats with early knee osteoarthritis and its JNK/NF-κB, SOX9 mechanisms / 中国应用生理学杂志

Objective: To investigate the repair effect and JNK/NF-κB,SOX9 mechanisms of vibration exercise with different frequencies on articular cartilage in rats with early knee osteoarthritis. Methods: Forty-eight adult male SD rats were randomly divided into six groups(n=8):model control group(MC),high frequency vibration group 1 (GP1,60 Hz),high frequency vibration 2 group (GP2,40 Hz),medium frequency vibration group (ZP,20 Hz),minor frequency group(DP,10 Hz)and normal control group(NC). Except for NC group,the rats in each group were made into early knee osteoarthritis model after six weeks of knee joint cavity injection of papain solution and 2% mixture l-cysteine on the 1st,4 th and 7th day. Each exercise group was subjected vibration to 40 minutes a day with amplitude of 2～5 mm and 5 days a week. Four weeks later, the articular cartilage of the lateral femoral condyle of the both back leg knee joints were detected by HE staining,serine O staining and Mankin scores for morphological observation. The expression levels of JNK,NF-κB p65 and Sox9 mRNA in articular cartilage of the medial femoral condyle were detected by RT-qPCR,and the protein expressions of JNK,NF-κB p65 and Sox9 were detected by Western blot. Results: Compared with the NC group,the Mankin score in other groups was significantly higher (P＜0.01). Compared with the MC group,the Mankin score of each vibration group was significantly lower(P＜0.05),the mRNA and protein expressions of JNK and NF-κB p65 in each vibration training group were significantly lower (P＜0.01),the expressions of Sox9 mRNA and protein in vibration training group were increased significantly (P＜0.01). Compared with the higher frequency group,the Mankin score,the mRNA and protein expressions of JNK and NF-κB p65 of lower frequency group were significantly lower (P＜0.05 or P＜0.01). But the expressions of Sox9 mRNA and protein were significantly higher (P＜ 0.05 or P＜0.01). Conclusion: Vibration exercise of different frequencies may present varying degrees of cartilage repair impact in rats with early knee osteoarthritis,and the cartilage repair by low-frequency vibration training is better than that by high-frequency vibration. This can be one of the mechanisms on controlling collagen synthesis by down-regulating JNK/NF-κB expression and increasing SOX9 activity of OA articular cartilage.

A randomized controlled trial of early intervention of external diaphragmatic electrical stimulation on diaphragmatic function in mechanically ventilated children / 中国小儿急救医学

Objective:To explore the effects of external diaphragm electrical stimulation on the diaphragm thickness and function in mechanically ventilated children.Methods:A randomized controlled trial was conducted in children who were admitted to PICU at Children′s Hospital of Fudan University and received mechanical ventilation between June 2021 and April 2022.The control group was given the routine treatment of mechanical ventilation, and the intervention group was given external diaphragm electrical stimulation in the early stage of mechanical ventilation in addition to routine treatment.Diaphragm thickness was continuously measured by bedside ultrasound every day for one week after mechanical ventilation, and the changing trend of diaphragm thickness was observed, and the diaphragmatic thickening fraction (DTf) and the incidence of ventilator-induced diaphragmtic dysfunction(VIDD) were calculated at the same time.Results:A total of 32 valid samples were included, including 15 cases in intervention group (10 males) and 17 cases in control group (11 males). The median age of the patients was 33 (10, 77) months, and the median duration of mechanical ventilation was 12 (8, 21) days.The reasons for mechanical ventilation in children included respiratory insufficiency in ten cases, brain dysfunction in ten cases, heart failure in eight cases, and postoperative surgery in four cases.The diaphragm end-expiratory thickness (DTe) in intervention group and the control group showed a gradually decreasing trend from the 1st day to the 7th day.The left thickness was reduced by 11% on the 7th day compared to 1st day in intervention group, which was reduced by 18% in control group; the average daily DTe was reduced by 2% per day in intervention group and by 3% per day in control group.The trends on the right and left were similar.The DTe thickness in the intervention group was greater than that in control group, among which, the mean DTe thickness in the left side of the intervention group on the 7th day was (0.110 7±0.023 7)cm, which was greater than that in control group (0.093 5±0.016 9)cm, and the difference was statistically significant ( t=-2.372, P<0.05); On the second day, the mean DTe thickness on the right side in the intervention group was (0.1267±0.0277) cm, which was greater than that in control group (0.104 7±0.018 1)cm, and the difference was statistically significant ( t=-2.688, P<0.05). DTf in the intervention group was lower than that in control group at 7th day, but the difference was not statistically significant(left DTf: adjusted mean difference was -0.117, P=0.088; right DTf: adjusted mean difference was -0.065, P=0.277). The incidence of VIDD in the intervention group was lower than that in control group(33.3% vs.41.2%), but the difference was not statistically significant ( χ2=0.005, P=0.946). Conclusion:External diaphragmatic electrical stimulation may be helpful for alleviating diaphragmatic atrophy in mechanically ventilated children.However, whether the improvement of diaphragm atrophy is beneficial to clinical outcome still needs further study.

Experience on prevention and control management in PICU during the epidemic of novel coronavirus Omicron variant in Shanghai / 中国小儿急救医学

Objective:To summarize the experience of the precise prevention and control strategy of novel coronavirus infection in the pediatric intensive care unit(PICU)during the epidemic of the Omicron variant.Methods:A retrospective analysis was performed on the strategies and management experience of precise prevention and control of novel coronavirus infection in PICU at Pediatric Hospital of Fudan University from March 1 to May 10, 2022.Results:According to the national and Shanghai novel coronavirus infection prevention and control standards, the PICU in our hospital, in accordance with the specialty characteristics of PICU, cooperated with the hospital′s department of infection and medical department to jointly construct a precise ward management strategy for the outbreak of the omicron mutants infection.Precise prevention and control management strategies were formulated from four aspects: the admission process of critically ill children, the division of PICU ward areas and nosocomial infection protection, the reception management system for children′s family members, and the " bubble management" system for PICU staff, and run them for 3 months.During the epidemic, there was no nosocomial infection of novel coronavirus infection in children or medical staff.During the period, a total of 140 critically ill children were admitted, including 87 cases transferred from the general ward in the hospital, 48 cases from the emergency department(non-febrile, 3 cases transferred by the transfer team), four cases from fever clinic, and one case from control ward.Four of the critically ill children had no emergency nucleic acid test report when they were admitted to the PICU.Among the 140 critically ill children, 54 patients received mechanical ventilation, 18 patients received blood purification, and two patients were monitored after liver transplantation.Seventy-eight (55.7%) children had underlying diseases.Conclusion:During the current round of novel coronavirus epidemic in Shanghai, PICU in our hospital formulated the admission and ward management procedures for critically ill children, which ensured the prevention and control of nosocomial infection of novel coronavirus, and at the same time ensured the treatment of critically ill children to the greatest extent.