The Exploration of Glymphatic System Alteration in Pediatric Acute Lymphoblastic Leukemia Using DTI-ALPS Method / 中山大学学报(医学科学版)

ObjectiveThe glymphatic system regulates cerebral spinal fluid and interstitial fluid transport which might be one of the pathways of central nervous system （CNS） leukemia at the early stage. This study aimed to investigate the alteration of glymphatic system based on diffusion tensor image-analysis along the perivascular space （DTI-ALPS） in pediatric acute lymphoblastic leukemia （ALL） without clinically diagnosed CNS infiltration. MethodsTwenty-five ALL and typically developing （TD） children were prospectively recruited， and all subjects underwent DTI. Group differences in brain water diffusivities and ALPS-index were evaluated using the analysis of covariance. The Spearman correlation analysis was used to evaluate the relationship between biological characteristics and significant parameters in pediatric ALL. ResultsCompared with TDs， decreased Dxassoc value （PFDR-corrected = 0.048） and increased Dzassoc value （PFDR-corrected = 0.033） were found in pediatric ALL. Hence， lower ALPS-index was found in children with ALL （PFDR-corrected < 0.001）. ALPS-index was negatively associated with the risk classification （rs = -0.47， P = 0.018） as well as immunophenotype （rs = -0.40， P = 0.046） in pediatric ALL. ConclusionsOur results show dysfunction of the glymphatic system is presented in pediatric ALL without clinically diagnosed CNS infiltration， which suggests that the glymphatic system might be one of pathway in the early-stage of ALL CNS infiltration. The DTI-ALPS method can be used to evaluate the change of glymphatic system， providing a new method for exploring the underlying mechanisms and early detection of pediatric ALL CNS infiltration.

Clinical features, gene mutation profile and prognosis analysis of diffuse large B-cell lymphoma complicated with follicular lymphoma / 白血病·淋巴瘤

Objective:To investigate the clinicopathologic characteristics, gene mutation profile and prognostic influencing factors of diffuse large B-cell lymphoma (DLBCL) complicated with follicular lymphoma (FL) (DLBCL/FL).Methods:The clinicopathological data of 50 DLBCL/FL patients admitted to Rui Jin Hospital Affiliated of Shanghai Jiao Tong University School of Medicine from February 2018 to November 2021 were retrospectively analyzed. Targeted sequencing was performed to assess the mutation profile of 55 lymphoma-related genes. The clinicopathological characteristics were summarized to evaluate the short-term therapeutic efficacy of all patients. Kaplan-Meier method was used to analyze the overall survival (OS) and progression-free survival (PFS) of patients. Cox regression risk models were used to assess the factors affecting the OS and PFS.Results:Among 50 DLBCL/FL patients, 23 cases (46%) were male, 22 cases (44%) had an international prognosis index (IPI) score ≥ 2 points, 16 cases (32%) were double-expression lymphoma (DEL) and 4 cases (8%) were double-hit lymphoma (DHL). The complete response (CR) and overall response rates were 68% (34/50) and 78% (39/50), respectively after the first-line therapy. The median follow-up time was 23.3 months (5.1-50.9 months). The 2-year OS rate was 82.1% and 2-year PFS rate was 67.1%; and the median OS and PFS were not reached. Targeted sequencing results showed that the mutation frequencies of KMT2D, MYD88, TP53, BTG2, DTX1, EZH2, CD70, CREBBP, DUSP2, HIST1H1C, HIST1H1E and PRDM1 genes in this cohort were more than 15%. Multivariate Cox regression analysis showed that male ( HR = 4.264, 95% CI 1.144-15.896, P = 0.031) and IPI score ≥ 2 points ( HR = 6.800, 95% CI 1.771-37.741, P = 0.007) were independent risk factors of PFS in newly diagnosed DLBCL/FL patients, and TP53 mutation ( HR = 4.992, 95% CI 1.027-24.258, P = 0.046) was an risk influencing factor of OS. Conclusions:The proportion of male and female DLBCL/FL patients is similar, with a small proportion of DHL. Mutations of KMT2D, MYD88 and TP53 genes are commonly found in DLBCL/FL patients. Generally, DLBCL/FL patients can have a high overall response and good prognosis. Male and IPI score ≥ 2 points are the independent risk factors of PFS, and TP53 mutation is an independent risk factor of OS in DLBCL/FL patients.

The Brain Structure Volume Estimation Based on Synthetic MRI in Pediatric Acute Lymphoblastic Leukemia / 中山大学学报(医学科学版)

ObjectiveCentral nervous system （CNS） infiltration commonly occurs in children with acute lymphoblastic leukemia （ALL）. Early subclinical CNS infiltration in pediatric ALL is hard to detect with conventional methods. This study aimed to investigate the changes of brain structure volume parameters based on Synthetic MRI （SyMRI） in pediatric ALL without clinically diagnosed CNS infiltration. MethodsThirty-six ALL and twenty-nine typically developing （TD） children were prospectively collected and all underwent SyMRI. The Synthetic MR software was used to obtain brain volumetric parameters including total white matter volume （WMV）， gray matter volume （GMV）， cerebrospinal fluid （CSF） volume， etc. and their within-group differences were assessed by analysis of covariance. The Spearman correlation analysis was used to examine the correlation between biological characteristics and statistically significant brain volume parameters. ResultsALL children showed increased CSF volume （PFDR-corrected = 0.009） and decreased GMV （PFDR-corrected = 0.027） when compared to TD children. We also found a moderately negative association between GMV/intracranial volume and risk classification in pediatric ALL （rs = -0.380， P = 0.022）. ConclusionsPediatric ALL without clinically diagnosed CNS infiltration presented with accumulation of CSF and reduction of gray matter. The brain volumetric changes in subclinical CNS infiltration of pediatric ALL provides a new attempt for exploring the underlying mechanism and early detection of CNS infiltration in pediatric ALL.

Clinical and genetic characteristics of children with primary dilated cardiomyopathy / 中国当代儿科杂志

OBJECTIVES@#To study the genetic characteristics, clinical characteristics, and prognosis of children with primary dilated cardiomyopathy (DCM).@*METHODS@#A retrospective analysis was performed on the medical data of 44 children who were diagnosed with DCM in Hebei Children's Hospital from July 2018 to February 2023. According to the genetic testing results, they were divided into two groups: gene mutation-positive group (n=17) and gene mutation-negative group (n=27). The two groups were compared in terms of clinical data at initial diagnosis and follow-up data.@*RESULTS@#Among the 44 children with DCM, there were 21 boys (48%) and 23 girls (52%). Respiratory symptoms including cough and shortness of breath were the most common symptom at initial diagnosis (34%, 15/44). The detection rate of gene mutations was 39% (17/44). There were no significant differences between the two groups in clinical characteristics, proportion of children with cardiac function grade Ⅲ or Ⅳ, brain natriuretic peptide levels, left ventricular ejection fraction, and left ventricular fractional shortening at initial diagnosis (P>0.05). The median follow-up time was 23 months, and 9 children (20%) died, including 8 children from the gene mutation-positive group, among whom 3 had TTN gene mutation, 2 had LMNA gene mutation, 2 had TAZ gene mutation, and 1 had ATAD3A gene mutation. The gene mutation-positive group had a significantly higher mortality rate than the gene mutation-negative group (P<0.05).@*CONCLUSIONS@#There is no correlation between the severity of DCM at initial diagnosis and gene mutations in children. However, children with gene mutations may have a poorer prognosis.

Recent research on childhood hypertrophic cardiomyopathy caused by MYH7 gene mutations / 中国当代儿科杂志

Hypertrophic cardiomyopathy (HCM) is the most common monogenic inherited myocardial disease in children, and mutations in sarcomere genes (such as MYH7 and MYBPC3) are the most common genetic etiology of HCM, among which mutations in the MYH7 gene are the most common and account for 30%-50%. MYH7 gene mutations have the characteristics of being affected by environmental factors, coexisting with multiple genetic variations, and age-dependent penetrance, which leads to different or overlapping clinical phenotypes in children, including various cardiomyopathies and skeletal myopathies. At present, the pathogenesis, course, and prognosis of HCM caused by MYH7 gene mutations in children remain unclear. This article summarizes the possible pathogenesis, clinical phenotype, and treatment of HCM caused by MYH7 gene mutations, in order to facilitate the accurate prognostic evaluation and individualized management and treatment of the children with this disorder.

Socio-demographic Characteristics and Nutritional Status of Adults at Risk of Type 2 Diabetes Mellitus in Kuala Nerus, Terengganu

@#Introduction: In Malaysia, the undiagnosed diabetes prevalence has increased. Socio-demographic characteristics and nutritional status play a crucial role in prediabetes development. Hence, this cross-sectional study aimed to identify the socio-demographic characteristics and nutritional status of adults at risk of T2DM in Kuala Nerus, Terengganu. Methods: A total of 30 participants at risk of T2DM aged 18 to 59 years old were recruited from Kuala Nerus using a convenience sampling method. Information on socio-demographic, anthropometric, fasting plasma glucose (FPG) level, clinical profile, Finnish Type 2 Diabetes Risk Assessment Tool (FINDRISC) score, dietary intake, and physical activity level were obtained. Results: The participants (mean age: 36.1 ± 8.7 years) were mostly female (76.7%), Malay (96.7%), married (43.3%), had a tertiary degree (60.0%), and were working (83.3%) with a monthly salary of less than RM 1000. Half of the participants were from the obese class I category. Their FPG level was 5.6 ± 0.5 mmol/L and half of them were classified as having optimal blood pressure. Also, they had a mean FINDRISC score of 6.3 ± 1.8. The participants consumed 2073 ± 247 kcal/day, which was comprised of 50.8% carbohydrate, 16.1% protein, and 33.1% fat. Most of them (63.3%) were minimally active. Conclusion: The participants had moderate T2DM risk with normal FPG level, blood pressure, and heart rate. They had excessive energy and fat intake with insufficient dietary fibre intake. It is vital to examine the socio-demographic characteristics and nutritional status, which can provide important information for planning future cost-effective T2DM preventive strategies.

Systemic thinking on family health promotion / 中华行为医学与脑科学杂志

In the systemic perspective, family is a system capable of self-organization, which possesses enough resources and ability to solve its own problems. To promote family health, the systemic therapists are required to consider each family member’s opinions and construction to certain problems, and assist them to discover and activate their own resources as well. Promoting family health also requires members to actively develop a sharing pattern within the family, exert the positive role of family rules, develop an authoritative parenting style so as to promote the mental health of children. Family members should ensure the clear and open boundaries between different subsystems, and maintain the stability of subsystem of the husband and wife especially. Furthermore, family members in different subsystems should make reasonable trade-offs and choices corresponding to different situations in order to both minimize conflicts and maintain the satisfying function of the family system. A healthy and ideal intimate relationship is interpreted from the systemic perspective of " evolvable, changeable, associative" on the core of " intimacy, passion and commitment" . The relationship will enhance partners' personal growth, in which the partners can not only examine its dynamic variations together but also deepen the understanding and acceptance of each other under the circumstances of bilateral original families and living environments. In addition, a healthy conjugal relationship has higher requirements such as " kinship" , commitment to two families of the couple and the children, and balancing the benefits between core family and original family.

The characteristics of non-alcoholic fatty liver disease and its associated factors in patients with rheumatoid arthritis / 中华预防医学杂志

Objective: To investigate the characteristics of non-alcoholic fatty liver disease (NAFLD) and its associated factors in rheumatoid arthritis (RA) patients. Methods: This cross-sectional study recruited 385 RA patients [including 72 (18.7%) male and 313 (81.3%) female] who received abdominal sonographic examination from August 2015 to May 2021 at Department of Rheumatology, Sun Yat-Sen Memorial Hospital. There were 28 RA patients at 16-29 years old and 32, 80, 121, 99, 25 at 30-39, 40-49, 50-59, 60-69, ≥ 70 years old, respectively. Demographic and clinical data were collected including age, gender, history of alcohol consumption, disease duration, body mass index (BMI), waist circumference, blood pressure, RA disease activity indicators and previous medications. Logistic regression analyses were used to identify the associated factors of NAFLD in RA patients. Results: The prevalence of NAFLD was 24.2% (93/385) in RA patients, 26.3% (21/80) in 40-49 age group and 33.1% (40/121) in 50-59 age group. There were 22.1% (85/385) and 3.6% (14/385) RA patients with overweight and obese, in which the prevalence of NAFLD was 45.9% (39/85) and 78.6% (11/14) respectively, which was 2.6 folds and 4.5 folds that of RA patients with normal BMI. Although there was no significant difference of age, gender and RA disease activity indicators between RA patients with or without NAFLD, those with NAFLD had higher proportions of metabolic diseases including obese (11.8% vs. 1.0%), central obesity (47.3% vs. 16.8%), hypertension (45.2% vs. 29.8%) and type 2 diabetes mellitus (24.7% vs. 12.0%), consistent with higher levels of total cholesterol [(5.33±1.31) mmol/L vs. (4.73±1.12) mmol/L], triglyceride [(1.51±1.08) mmol/L vs. (0.98±0.54) mmol/L] and low-density lipoprotein cholesterol [(3.37±0.97) mmol/L vs. (2.97±0.78) mmol/L, all P<0.05]. Multivariate logistic regression analysis showed that BMI (OR=1.314) and triglyceride (OR=1.809) were the independent factors positively associated with NAFLD in RA patients. Conclusion: NAFLD is a common comorbidity in RA patients, especially in those with middle-aged, overweight or obese, which is associated with high BMI or high triglyceride. Screening and management of NAFLD in RA patients especially those with overweight, obese or dyslipidemia should be emphasized.

ZHANG Wei-hua's experience in clinical treatment of somatalgia with "point-zone-strip stimulation technique" of acupuncture / 中国针灸

The clinical experience in treatment of somatalgia with "point-zone-strip stimulation technique" of acupuncture of professor ZHANG Wei-hua was summarized. Professor ZHANG integrates the theories of the cutaneous region of meridian, biaoben, "taking tender point as acupoint" and local holography as a whole in treatment of somatalgia. The "point-stimulation technique" of acupuncture (subcutaneous needling technique) is adopted for the painful site less than 3 cm in diameter, the "zone-stimulation technique" (surrounding needling technique) is for the site larger than 3 cm in diameter and the "strip-stimulation technique" (cubit-tibia needling technique) is for various acute and chronic somatalgia. These three needling techniques are applicable singly or in combination in clinical practice.

Expert Consensus on Sepsis Responding Specifically to Traditional Chinese Medicine / 中国实验方剂学杂志

To give full play to the therapeutic advantages of traditional Chinese medicine （TCM） in sepsis， clarify the entry point of integrated TCM and western medicine， further standardize the clinical treatment of TCM， develop a recognized and integrated treatment protocol of TCM and western medicine， and improve the clinical efficacy on sepsis，the Chinese Association of Chinese Medicine organized TCM and western medicine experts specialized in sepsis treatment to conduct in-depth discussions on the advantages of TCM and integrated TCM and western medicine in the treatment of sepsis based on the TCM etiology and pathogenesis of sepsis， a representative acute and critical disease. They emphasized the pathogenesis characteristics of asthenia of healthy Qi and sthenia of pathogenic factors and summarized the roles of Chinese medicine in correcting the imbalance of inflammatory response， improving blood coagulation dysfunction， and relieving organ damage. Furthermore， they proposed the treatment protocol with integrated TCM and western medicine， which is expected to provide references for actual clinical treatment and scientific research.

Exploration and practice of benefit evaluation for medical equipments based on objectives and key results / 中华医院管理杂志

The study aims to improve the level of fine management of medical equipments, give full play to the functions and roles for better patient service, and explore methods for evaluating the benefits of medical equipment that can take into account and reflect the needs of multiple parties. Based on objectives and key results(OKR) methods and concepts, a benefit evaluation system was developed with the goal of giving full play to the functions and roles of medical equipments, with corresponding evaluation indexes and supervision and evaluation mechanisms formulated as well. This index system could take into account the needs and concerns of hospitals, the departments in use, the management authorities and patients at large, while contributing to process supervision and continuous improvement. In the OKR practice of large medical equipments(CT, MR) from 2018 to 2019, they had performed significantly better in inspections, inspection positive coincident rates, clinical service capabilities, maintenance assurance levels, patient satisfaction, scientific research and academics among others. The use of a medical equipment benefit evaluation system based on OKR concepts and methods can provide effective evaluation indicators for the operation and management of medical equipments. In addition, the system can maintain internal improvement momentum leveraging process supervision and continuous improvement methods, in order to assure the elevation of fine management level of medical equipments of modern hospitals, thus offering better medical services for patients at large.

Effect and Mechanism of Fuzheng Touxie Prescription on Immune Homeostasis of Drug-resistant Pseudomonas aeruginosa Lung Infection Rats / 中国实验方剂学杂志

Objective:To investigate the effect and mechanism of Fuzheng Touxie prescription （FZTX） on the immune homeostasis of drug-resistant <italic>Pseudomonas aeruginosa</italic> lung infection in rats at different time points. Method:A total of 168 rats were divided into a blank group （<italic>n</italic>=8），a model group （<italic>n</italic>=40），a Touxie （TX） group （<italic>n</italic>=40），an early Fuzheng （FZ） group （<italic>n</italic>=40）， and a delayed FZ group （<italic>n</italic>=40）. The blank group was given distilled water by gavage， the model group was given distilled water by gavage after infection，the TX group was given clear heat and penetrate evil drug free decoction granules（3.5 g·kg^-1） by gavage after infection， the early FZ group was given Fuzheng Touxie whole formula free decoction granules（10.75 g·kg^-1） by gavage after infection， the delayed FZ group was given clear heat and penetrate evil drug free decoction granules by gavage after infection， on the third day plus Fuzheng drug free decoction granules［（3.5+10.75） g·kg^-1］ by gavage， the three treatment groups were gavaged twice a day， 2 mL each time .Each drug treatment group was divided into five groups according to five time points （3 h，1 d，3 d，5 d， and 7 d）， with eight rats in each group. The levels of tumor necrosis factor-<italic>α</italic>（TNF-<italic>α</italic>），high mobility group protein 1（HMGB1），interleukin-10（IL-10）， and tumor necrosis factor -<italic>α</italic>-induced protein-8-like2 （TIPE2） were measured by enzyme-linked immunosorbent assay （ELISA）， and HMGB1 protein expression level by Western blot. Result:At 3 h，the TNF-<italic>α</italic> content in the drug treatment groups was higher than that in the blank group and the model group （<italic>P</italic><0.05）. At 3 d，the TNF-<italic>α</italic> content in the early FZ group and the delayed FZ group was lower than that in the model group （<italic>P</italic><0.05） and the TX group （<italic>P</italic><0.05）. At 1 d，the HMGB1 content in the TX group and the delayed FZ group was higher than that in the model group （<italic>P</italic><0.05）. At 5 d，the HMGB1 content was lower in the delayed FZ group than in the model group （<italic>P</italic><0.05）. At 7 d，HMGB1 protein expression in the model group was higher than that in the blank group （<italic>P</italic><0.05） and the early FZ group （<italic>P</italic><0.05）. At 3 d，the IL-10 content was significantly higher in both the early FZ group and the delayed FZ group than that in the model group （<italic>P</italic><0.05）. At 5 d，the IL-10 content was higher in the early FZ group than that in the TX group （<italic>P</italic><0.05）. At 7 d，the IL-10 content in the early FZ group and the delayed FZ group was lower than that in the TX group （<italic>P</italic><0.05）. At 5 d，the TIPE2 content in the early FZ group was lower than that in the model group （<italic>P</italic><0.05）. At 7 d，the TIPE2 content in the TX group and the delayed FZ group was lower than that in the model group （<italic>P</italic><0.05）. Conclusion:FZTX or modified prescription can promote the inflammatory response to eliminate pathogenic bacteria in the early stage and suppress the inflammatory response in the late stage to avoid the inflammatory cascade effect and lung tissue damage，indicating that Fuzheng drugs have an important role in maintaining the immune homeostasis of the body after infection.

Transcriptomic profile of human erythroleukemia cells in response to Sargassum fusiforme polysaccharide and its structure analysis / 中国天然药物

Sargassum fusiforme (S. fusiforme) has been used as an ingredient in Chinese herbal medicine for thousands of years. However, there are a limited number of studies concerning its therapeutic mechanism. High performance gel permeation chromatography (HPGPC) analysis showed that the average molecular weight of the S. fusiforme polysaccharide, SFPS 191212, is 43 kDa. SFPS 191212 is composed of mannose, rhamnose, galactose, xylose, glucose, and fucose (at a molar ratio: 2.1 : 2.9 : 1.8 : 15.5 : 4.6 : 62.5) with α- and β-configurations. The present research evaluated the anti-tumor potential of the S. fusiforme polysaccharide in human erythroleukemia (HEL) cells in vitro. To explore the SFPS 191212's apoptosis mechanism in HEL cells, transcriptome analysis was performed on HEL cells that were incubated with SFPS 191212. The inhibitory effect of SFPS 191212 on HEL cell growth was also analyzed. It was found that SFPS 191212 inhibited HEL cell proliferation, reduced cell viability in a concentration-dependent manner, and induced an insignificant toxic effect on normal human embryonic lung (MRC-5) cells. Compared with the control group, transcriptome analysis identified a total of 598 differentially expressed genes (DEGs), including 243 up-regulated genes and 355 down-regulated genes. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed on all DEGs, and 900 GO terms and 52 pathways were found to be significantly enriched. Finally, 23 DEGs were randomly selected and confirmed by quantitative real-time polymerase chain reaction (qRT-PCR). Moreover, SFPS 191212 down-regulated the PI3K/Akt signal transduction pathway. Our results provide a framework for understanding the effect of SFPS 191212 on cancer cells and can serve as a resource for delineating the anti-tumor mechanisms of S. fusiforme.

Genetic analysis of 46,XY disorders of sex development in children caused by a new NR5A1 gene variant / 中华医学遗传学杂志

OBJECTIVE@#To explore the genetic basis for a child with 46,XY disorders of sex development (DSD) and explore its genotype-phenotype correlation.@*METHODS@#The child was subjected to whole exome sequencing (WES), and exons 1 to 7 of NR5A1 were subjected to multiplex ligation-dependent probe amplification (MLPA) analysis.@*RESULTS@#The patient presented with rudimentary vulva of a female with Tanner stage 1. B-mode ultrasonography has detected ovary and uterus. The child was found to have a chromosome karyotype of 46,XY. WES revealed that the patient has harbored heterozygous deletion of exon 5 of the NR5A1 gene, which was a novel pathogenic variant inherited from the mother. No abnormality was found in the father.@*CONCLUSION@#The main symptoms of 46,XY DSD children are insufficient external genitalia masculinization, for which variants of the NR5A1 gene are an important cause. WES has improved the detection rate of genetic variants and provided a solid basis for genetic counseling of the affected families.

An unexpected electrocardiogram sign of subacute left ventricular free wall rupture: Its early awareness may be lifesaving / 世界急诊医学杂志（英文）

@#BACKGROUND: Post-infarct left ventricular free wall rupture (LVFWR) is not always an immediately catastrophic complication. The rupture can be subacute, allowing time for diagnosis and intervention. Accordingly, early recognition of the entity may be lifesaving. METHODS: We present an electrocardiogram (ECG) change pattern in two cases, which was erroneously attributed to ischemia. Two women in their 80s were admitted to our institute after experiencing the sudden onset of chest pain. They were managed as anterior ST-segment elevation myocardial infarction without reperfusion treatment. Unfortunately, they experienced a recurrence of severe chest pain with cardiogenic shock during hospitalisation. The ECG recorded at that time showed a ST-segment re-elevation in infract-related leads. RESULTS: The two cases were regrettably received a misjudgement of reinfarction at first, and one of the patients even was administrated with tirofi ban. Afterwards the diagnosis of subacute LVFWR was made through antemortem echocardiography. CONCLUSION: New ST-segment elevation (STE) in infarct-associated leads, coupled with recurrence of chest pain and new-onset hypotension, may constitute the premonitory signs of a subacute LVFWR.

Exploration of the molecular mechanism of Lishi-Kuijie decoction in the treatment of ulcerative colitis based on network pharmacology / 药学学报

We used network pharmacology and molecular docking to investigate the molecular mechanism of Lishi-Kuijie decoction (KJF) in the treatment of ulcerative colitis (UC). Chemical components and targets related to the 13 herbs of Chinese Materia Medical in KJF were searched through the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP). The UC-related targets were identified through OMIM, DisGeNet and GeneCards databases. Using Cytoscape 3.7.2 software a drug-compound-disease-target network was established. The target interaction network and core target for KJF against UC was built and selected based on the String database and topological parameters. Using the R package clusterprofile in Bioconductor, the intersection genes and the disease-drug intersection targets were transformed to Entrez gene ID, followed by gene ontology biological process enrichment analysis and KEGG pathway annotation analysis. The KJF compound-UC target network contained 149 compounds, 108 corresponding targets and 12 core targets (including signal transducer and activator of transcription 3, interleukin 6, tumor necrosis factor, c-x-c motif chemokine ligand 8, interleukin 2, etc.). We identified 2 371 GO terms and 155 pathways (mainly involving IBD, PI3K-ATK, NF-kappa B, TNF, Toll-like receptor signaling pathway) as determined by enrichment analysis. Molecular docking, used with the key molecular factors and the core targets, revealed stable binding for IL2, TNF-α, MAPK1 and RELA. These results suggest the possible molecular mechanism of KJF in treatment of UC and lay the foundation for further characterization of the components and their mechanisms.

Effect of Sargassum fusiforme polysaccharide on apoptosis and its possible mechanism in human erythroleukemia cells / 中国天然药物

This study aimed to investigate the effects of Sargassum fusiforme polysaccharide (SFPS I, II, and III) on the apoptosis and regulation of human erythroleukemia (HEL) cells. The effect of different doses of SFPS on HEL cell growth was detected using the Cell Counting Kit-8 method, and apoptosis was detected by Hoechst staining. Cell cycle distribution and apoptosis were detected using flow cytometry. Expression of the cell cycle gene, p53, antiapoptotic genes, Bcl-xL and Bcl-2, and pro-apoptotic genes, Bax, Bad, and Caspase-3, as well as the expression of the corresponding proteins, were detected using real-time quantitative polymerase chain reaction (qPCR) and Western blot. The results showed that SFPS II and III decreased HEL cell viability and induced HEL cell apoptosis. Different concentrations of SFPS (I, II, and III) were detected that induced much less toxic effect in normal human embryonic lung (MRC-5) cells, and SFPS I increased cell proliferation, indicating its favorable selectivity towards cancer cells. The mechanism by which SFPS induced apoptosis was also found to be related to the induction of cell cycle arrest in the G/G phase and the increased expression of apoptosis-related genes and proteins. We concluded that SFPS induces HEL cell apoptosis, possibly via activation of the Caspase pathway, providing the theoretical basis for the development of SFPS-based anti-tumor drug products.

Utility of cross-sectional area of erector spinae muscle combined with serum GDF-15 for the diagnosis and prognosis assessment of ICU-acquired weakness in mechanically ventilated patients / 中华急诊医学杂志

Objective:To identify the clinical correlations between the cross-sectional area loss of the erector spinae muscle (ESMcsa Loss) and serum growth differentiation factor-15 (GDF-15) in mechanically ventilatied patients in ICU. In addition, to investigate their diagnostic value for ICU-acquired weakness (ICU-AW) and their predictive value for 60-day survival in mechanically ventilated patients.Methods:Ninety-two patients with acute respiratory failure, who required mechanical ventilation therapy, were randomly selected among hospitalized patients from June 2018 to November 2019. The serum GDF-15 level was detected by ELISA, the total cross-sectional area of the right and left erector spinae muscles was calculated by CT images, and the patient's muscle strength was assessed using the British Medical Research Council (MRC) muscle strength score on day 1 and day 7. The patients were divided into the ICU-AW group and the non-ICU-AW group according to the MRC-score on the 7th day of ICU admission. The correlations between plasma GDF-15 level, ESMcsa loss, and MRC score on day 7 were investigated. The receiver operating characteristic (ROC) curve was used to calculate the predictive value of serum GDF-15, ESMcsa loss, and ESMcsa loss ratio on day 7 of mechanically ventilated patients in the diagnosis of ICU acquired muscle weakness. Moreover, the predictive value of GDF-15 and ESMcsa loss ratio on the 90-day survival status of the patients was assessed using survival curves.Results:Ninety-two patients were enrolled. According to whether the MRC-score on the 7th day was less than 48, 49 cases were included in the ICU-AW group and 43 cases in the non-ICU-AW group. The mechanical ventilation time, length of ICU stay and length of hospital stay in the ICU-AW group were higher than those in the non-ICU-AW group, and there were no significant differences in other baseline indicators. There were no significant differences in serum GDF-15, ESMcsa and MRC-score between the two groups on day 1. The GDF-15 level in the ICU-AW group was significantly higher than that in the non-ICU-AW group while ESMcsa and MRC-score were significantly lower than those in the non-ICU-AW group on day 7 [GDF-15 (pg/mL): 2529.53±625.67 vs. 1614.21±567.18; ESMcsa (cm 2): 23.76±6.85 vs. 29.15±6.5; MRC-1score: 41.10±3.35 vs. 51.23±2.84; all P <0.001]. ESMcsa loss and ESMcsa loss ratio were significantly positively correlated with serum GDF-15 levels on day 7 ( r = 0.2355 and 0.3192, respectively). ESMcsa loss and ESMcsa loss ratio were significantly negatively correlated with MRC-score ( r = -0.3072 and -0.3527, respectively). The ROC curve analysis showed that plasma GDF-15 level, ESMcsa loss, and ESMcsa loss ratio on day 7 had predictive value for ICU-AW diagnosis in mechanically ventilated patients [Areas under the ROC curve (AUC) were 0.904, 0.835, and 0.889, all P <0.001]. The 60-day survival curve demonstrated that the survival rate was 60.0% in the high GDF-15 group, while was 77.8% in the low GDF-15 group; and was 60.0% in the high ESMcsa loss ratio group, while was 80.0% in the low ESMcsa loss ratio group (all P<0.05). Conclusions:There was a significant correlation between the cross-sectional area loss of the erector spinae muscle and the increase of serum GDF-15 level after 7 days of mechanical ventilation in ICU, suggesting the acute muscle wasting and skeletal muscle hypofunction, which has certain diagnostic value for ICU-AW, and can predict the 60-day survival status of mechanically ventilated patients in ICU.

Epilepsy in Southeast Asia, how much have we closed the management gap in past two decades?

@#The last review on epilepsy in Southeast Asian (SEA) countries was reported in 1997. This review aimed to update the understanding of epilepsy management in this region over the past 23 years. There has been significant increase in the epidemiological studies which reported a prevalence of 4.3-7.7 per 1,000 populations in this region. Reversible aetiologies of epilepsy such as head injury, birth trauma, cerebrovascular disease, and intracranial infections (neurocysticercosis or meningoencephalitis) are still prevalent, with a surge in autoimmune encephalitis. There was a surge in genetic studies which suggest ethnic variation. Treatment gap is still high especially in the rural and less developed areas, and the availability and affordability of newer anti-epileptic drugs (AEDs) is still a major challenge in SEA. Alternative medicine is a common practice but varies among different ethnic groups. AEDs hypersensitivity especially on the association between HLA-B*1502 and carbamazepine-related severe cutaneous reaction had been extensively studied and proven in nearly all SEA countries. However, HLA-B*1502 screening is not widely available in SEA and the cost-effectiveness of the screening is questionable. Stigma and its psychosocial consequences are still a major concern despite enormous efforts to study the public attitudes towards epilepsy and change of epilepsy naming in a few countries. The number and complexity of epilepsy surgery are progressing, but it is still under-utilized in many SEA countries, related to cost, cultural perception and lack of facilities. More resources should also be channelled in training adequate number of epileptologists who can spearhead epilepsy care around the region, as well as public education and research in epilepsy. In conclusion, there is an increase in epilepsy research in this region, gradual increase in trained neurologists and facilities, and efforts to reduce the knowledge and treatment gap, but the epilepsy management gap is still a battle to fight.

Knowledge, Attitude and Practice (KAP) Regarding Non-Surgical Intervention Among Osteoarthritis Patients: A Review

@#Treatment effectiveness depends on the knowledge, attitude, and practice (KAP) of osteoarthritis (OA) patients towards their assigned treatment. This study aimed to explore the KAP towards non-surgical intervention among OA patients. A methodological framework proposed by Arksey and O’Malley (2005) was implemented. An electronic database search of English-language academic articles was conducted using PubMed and ScienceDirect databases encompassing 1998 to 2018 period of time, resulting in a total of 26 studies. OA patients were knowledgeable about the disease and exercise management. However, they were lack of knowledge on drug therapy and complementary strategies. The attitude towards non-surgical interventions was ambivalence. Lastly, the practice section mainly focused on patients’ compliance and behaviour towards different conservative managements, namely physiotherapy, medications, and complementary and alternative medicines (CAMs) which influenced by both knowledge level and attitudes. In conclusion, a higher knowledge level and positive attitude will result in good practice.