Uso de ibuprofeno en el tratamiento de pacientes pediátricos con poliuria y disnatremia. Reporte de una serie de casos / Ibuprofen use for the treatment of pediatric patients with polyuria and dysnatremia. A case series report

Los niños con lesiones selares y/o supraselares pueden presentar diabetes insípida central con posterior secreción inadecuada de hormona antidiurética. Nosotros observamos, en algunos casos, aumento de la incidencia de poliuria, natriuresis e hiponatremia, tríada diagnóstica del síndrome cerebral perdedor de sal. Aquí comunicamos la evolución de 7 pacientes con antecedentes de daño agudo del sistema nervioso central y diabetes insípida central seguida por síndrome cerebral perdedor de sal. Como tratamiento aportamos secuencialmente fluidos salinos parenterales, cloruro de sodio oral, desmopresina, mineralocorticoides e incluso tiazidas. Ante la persistencia de poliuria con hiponatremia, agregamos ibuprofeno. Como resultado de este esquema terapéutico secuencial, este grupo redujo significativamente los valores de diuresis diaria de 10 ml/kg/h a 2 ml/kg/h en un tiempo promedio de 5 días, normalizando también las natremias (de 161 mEq/L a 143 mEq/L) en un tiempo promedio de 9 días. En ningún caso observamos efectos adversos asociados al tratamiento.

Children with sellar and/or suprasellar lesions may develop central diabetes insipidus with subsequent inappropriate antidiuretic hormone secretion. An increased incidence of polyuria, natriuresis, and hyponatremia has been reported in some cases, which make up the diagnostic triad of cerebral salt wasting syndrome. Here we report the clinical course of 7 patients with a history of acute central nervous system injury and central diabetes insipidus followed by cerebral salt wasting syndrome. Treatment included the sequential use of parenteral saline solution, oral sodium chloride, desmopressin, mineralocorticoids, and even thiazides. Due to persistent polyuria and hyponatremia, ibuprofen was added. As a result of this sequential therapeutic regimen, daily urine output reduced significantly from 10 mL/ kg/h to 2 mL/kg/h over an average period of 5 days, together with a normalization of natremia (from 161 mEq/L to 143 mEq/L) over an average period of 9 days. No treatment-related adverse effects were observed in any case.

Exploring the Pathogenesis of T2DM based on the Correlation between “Qi-fire Imbalance” and Ferroptosis / 中医杂志

Ferroptosis is a novel iron-dependent mode of programmed cell death characterized by iron deposition and accumulation of lipid peroxidation. More and more studies have found that ferroptosis is closely related to the pathogenesis of type 2 diabetes mellitus （T2DM）. The yin-fire theory is an important part of LI Gao's spleen-stomach theory， and it is believed that qi-fire imblance and yin-fire internal generation is the main pathogenesis of T2DM. Abnormal iron metabolism may be an important prerequisite for T2DM yin-fire internal generation， while oxidative stress is the specific manifestation of T2DM qi-fire imbalance. Reactive oxygen species （ROS） is the end product of qi-fire imbalance， and lipid peroxide is the pathological products of T2DM yin-fire internal generation. This study intends to explore the pathological mechanism of qi-fire imbalance and yin-fire internal generation from the perspectives of iron metabolism， oxidative stress and lipid peroxidation， enriching the modern connotation of yin-fire theory， and benefiting traditional Chinese medicine to target against ferroptosis， and prevent and treat T2DM precisely.

Current situation and related factors of occupational stress of employees of a petrochemical enterprise / 环境与职业医学

Background Occupational stress has become one of the main factors affecting people's physical and mental health, and there are many sources of occupational stress in petrochemical enterprises. Objective To evaluate the current situation of occupational stress and its related factors among employees in a petrochemical enterprise, and to provide a scientific basis for reduing the risk of occupational stress among employees in petrochemical enterprises. Methods In June 2022, a cross-sectional questionnaire survey was conducted in a petrochemical enterprise in Hainan, including a general information questionnaire for basic information, the Effort-Reward Imbalance (ERI) for occupational stress, and the Pittsburgh Sleep Quality Index (PSQI) for sleep quality. Chi-square test was used to compare differences in positive occupational stress by demographic characteristics, occupational characteristics, behavior, and occupational disease hazards. Logistic regression was employed to evaluate factors associated with occupational stress. Results Of the 1129 questionnaire distributed, a total of 999 valid questionnaire were returned,with a valid recovery rate of 88.5%. The positive rate of occupational stress among employees in the petrochemical enterprise was 29.5%. There were statistically significant differences in the positive rate of occupational stress among the employees grouped by gender, age, marital status, body mass index (BMI), monthly income, length of service, smoking, weekly working hours, type of work, working mode, sleep quality, noise exposure, and high temperature exposure (P<0.05). In terms of positive occupational stress among subcategories: workers being male (vs. female), working ＞40 h per week (vs. ≤40 h per week), regular day shift (vs. shift work), smoking (vs. not smoking), with exposure to noise and heat (vs. without such exposure), and having poor sleep quality (vs. good sleep quality) reported higher positive occupational stress rates (P＜0.05). The results of pairwise comparison showed that the positive rate of occupational stress in divorced (50.0%) or married (32.0%) workers was higher than that in single (27.1%) workers, and higher in operation workers (30.6%) than in other types of work (20.5%) (P＜0.05). The trend chi-square results showed that the positive rate of occupational stress increased linearly with the increase of age, length of service, BMI, or monthly income (P＜0.05). The results of logistic regression analysis after adjustment showed that workers who worked ＞40 h a week had a higher risk of occupational stress than those who worked ≤40 h a week, and the OR (95%CI) was 1.909 (1.135, 3.211); the workers of other types of work had a lower risk of reporting occupational stress than operation workers, and the OR (95%CI) was 0.513 (0.272, 0.968); the workers with noise exposure had a higher risk of occupational stress than the workers without, and the OR (95%CI) was 2.457 (1.070, 5.642). Conclusion The positive rate of occupational stress among employees in this petrochemical enterprise is high. Among them, operators, working hours per week＞40 h, and noise exposure may increase the incidence of occupational stress. The enterprise should actively take measures to reduce the occurrence of occupational stress among employees.

Mining and analysis of the ADE signals of avapritinib based on FAERS database / 中国药房

OBJECTIVE To provide reference for clinically safe application of avapritinib. METHODS The adverse drug event （ADE） reports of avapritinib from January 9th，2020，to September 30th，2022 were collected from FDA Adverse Event Reporting System （FAERS） database. For data mining and analysis，reporting odds ratio （ROR） method and proportional reporting ratio （PRR） method in the proportional imbalance method were utilized. RESULTS A total of 10 895 ADE reports with avapritinib as the main suspect drug were gathered，and 201 ADE signals involving 19 systematic organ classifications were found after eliminating invalid signals. The instruction of the drugs did not mention any of the ADE，including tinnitus，dementia，chilly limbs， the reduction of blood iron，the reduction of blood sugar，fever，the reduction of vitamin D and vitamin B12，as well as all ADE in the 2 SOCs of musculoskeletal and connective tissue illnesses，diseases of the reproductive system，and diseases of the breast. The majority of the ADE reports 670 cases with complete drug information were for the nervous system （230 cases，accounting for 34.33%） and ocular organ （277 cases，accounting for 41.34%）. Compared with other systems，daily dose and treatment course showed significant effects on ADE of neurological system and ocular organ （P＜0.05），and the patient’s age had a significant impact on the ADE of the nervous system （P＜0.05）. CONCLUSIONS A greater incidence of ADE after using avapritinib is present in patients older than 65 with a daily dose of 300 mg/d and a treatment period lasting between 31 and 90 days； patients receiving a daily dose of 300 mg/d and a treatment regimen lasting 31 to 90 days are more likely to experience ADE of the ocular organ. Attention should be given to the aberrant symptoms of the patient’s eyes and nervous system throughout clinical use of avapritinib，and prompt intervention should be given.

Class-imbalance Prediction and High-dimensional Risk Factor Identification of Adverse Reactions of Traditional Chinese Medicine with Centralized Monitoring in Real-world Hospitals / 中国实验方剂学杂志

ObjectiveTo achieve high-dimensional prediction of class imbalanced of adverse drug reaction（ADR） of traditional Chinese medicine（TCM） and to classify and identify risk factors affecting the occurrence of ADR based on the post-marketing safety data of TCM monitored centrally in real world hospitals. MethodThe ensemble clustering resampling combined with regularized Group Lasso regression was used to perform high-dimensional balancing of ADR class-imbalanced data， and then to integrate the balanced datasets to achieve ADR prediction and the risk factor identification by category. ResultA practical example study of the proposed method on a monitoring data of TCM injection performed that the accuracy of the ADR prediction， the prediction sensitivity， the prediction specificity and the area under receiver operating characteristic curve（AUC） were all above 0.8 on the test set. Meanwhile， 40 risk factors affecting the occurrence of ADR were screened out from total 600 high-dimensional variables. And the effect of risk factors on the occurrence of ADR was identified by classification weighting. The important risk factors were classified as follows：past history， medication information， name of combined drugs， disease status， number of combined drugs and personal data. ConclusionIn the real world data of rare ADR with a large amount of clinical variables， this paper realized accurate ADR prediction on high-dimensional and class imbalanced condition， and classified and identified the key risk factors and their clinical significance of categories， so as to provide risk early warning for clinical rational drug use and combined drug use， as well as scientific basis for reevaluation of safety of post-marketing TCM.

Exploring the Pathogenesis of T2DM based on the Correlation between “Qi-fire Imbalance” and Ferroptosis / 中医杂志

@#Ferroptosis is a novel iron-dependent mode of programmed cell death characterized by iron deposition and accumulation of lipid peroxidation. More and more studies have found that ferroptosis is closely related to the pathogenesis of type 2 diabetes mellitus （T2DM）. The yin-fire theory is an important part of LI Gao's spleen-stomach theory， and it is believed that qi-fire imblance and yin-fire internal generation is the main pathogenesis of T2DM. Abnormal iron metabolism may be an important prerequisite for T2DM yin-fire internal generation， while oxidative stress is the specific manifestation of T2DM qi-fire imbalance. Reactive oxygen species （ROS） is the end product of qi-fire imbalance， and lipid peroxide is the pathological products of T2DM yin-fire internal generation. This study intends to explore the pathological mechanism of qi-fire imbalance and yin-fire internal generation from the perspectives of iron metabolism， oxidative stress and lipid peroxidation， enriching the modern connotation of yin-fire theory， and benefiting traditional Chinese medicine to target against ferroptosis， and prevent and treat T2DM precisely.

Safety signal mining of FOLFOX scheme and FOLFIRI scheme-induced hepatotoxicity / 中国药房

OBJECTIVE To mine the safety signals of FOLFOX scheme and FOLFIRI scheme-induced hepatotoxicity， and to provide reference for the selection of clinical rational treatment plan and the prevention and treatment of drug adverse reaction （ADR）. METHODS Reporting odds ratio method and proportion report ratio method were used to analyze adverse drug event （ADE） reports of FOLFOX scheme and FOLFIRI scheme in FDA adverse event reporting system during January 1， 2004-June 30， 2022. The potential safety signals of FOLFOX scheme and FOLFIRI scheme-induced hepatotoxicity were mined. RESULTS The amounts of ADE reports related to FOLFOX scheme and FOLFIRI scheme were respectively 3 454 and 1 359； the proportions of male and female patients involved were 1.50∶1 and 1.67∶1 in these two schemes， respectively. The top five countries with the largest number of reports were the United States， Japan， France， Italy and the United Kingdom， respectively accounting for 58.48% and 53.79% of the total reported cases. More than 90% of patients took no more than 5 drugs in combination， the proportion of patients receiving FOLFOX scheme and FOLFIRI scheme combined with anti-angiogenic drugs or epidermal growth factor receptor inhibitors was 45.45% and 86.82%， respectively. Totally 443 ADE reports of FOLFOX scheme-induced hepatotoxicity were collected， and 22 ADR signals were generated， including hepatic sinusoidal obstruction syndrome， nodular regenerative hyperplasia， drug-induced liver injury， blood bilirubin increased， etc. Totally 128 ADE reports of FOLFIRI scheme- induced hepatotoxicity were reported， and 9 ADR signals were generated， including blood bilirubin increased， hepatotoxicity， steatohepatitis， hepatic steatosis， etc. CONCLUSIONS FOLFOX scheme and FOLFIRI scheme can cause different types of hepatotoxicity. Clinical drug monitoring should be strengthened to guarantee drug safety.

Total Glucosides of Paeony Regulate Immune Imbalance Mediated by Dermal Mesenchymal Stem Cells in Psoriasis Mice / 中国结合医学杂志

OBJECTIVE@#To investigate the therapeutic effects of total glucosides of paeony (TGP) on psoriasis based on the immunomodulatory effect of dermal mesenchymal stem cells (DMSCs).@*METHODS@#A total of 30 male BALB/c mice were divided into 6 groups (n=5 in each) by a random number table method, including control, psoriasis model (model, 5% imiquimod cream 42 mg/d), low-, medium- and high-dose TGP (50, 100, and 200 mg/kg, L, M-, and H-TGP, respectively), and positive control group (2.5 mg/kg acitretin). After 14 days of continuous administration, the skin's histopathological changes, apoptosis, secretion of inflammatory cytokines, and proportion of regulatory T cells (Treg) and T helper cell 17 (Th17) were evaluated using hematoxylin-eosin (HE) staining, TdT-mediated dUTP nick end labeling staining, enzyme-linked immunosorbent assay, and flow cytometry, respectively. DMSCs were further isolated from the skin tissues of normal and psoriatic mice, and the cell morphology, phenotype, and cycle were observed. Furthermore, TGP was used to treat psoriatic DMSCs to analyze the effects on the DMSCs immune regulation.@*RESULTS@#TGP alleviated skin pathological injury, reduced epidermis layer thickness, inhibited apoptosis, and regulated the secretion of inflammatory cytokines and the proportion of Treg and Th17 in the skin tissues of psoriatic mice (P<0.05 or P<0.01). There was no significant difference in cell morphology and phenotype between control and psoriatic DMSCs (P>0.05), however, more psoriatic DMSCs remained in G0/G1 phase compared with the normal DMSCs (P<0.01). TGP treatment of psoriatic DMSCs significantly increased cell viability, decreased apoptosis, relieved inflammatory response, and inhibited the expression of toll-like receptor 4 and P65 (P<0.05 or P<0.01).@*CONCLUSION@#TGP may exert a good therapeutic effect on psoriasis by regulating the immune imbalance of DMSCs.

A survey of loss function of medical image segmentation algorithms / 生物医学工程学杂志

Medical image segmentation based on deep learning has become a powerful tool in the field of medical image processing. Due to the special nature of medical images, image segmentation algorithms based on deep learning face problems such as sample imbalance, edge blur, false positive, false negative, etc. In view of these problems, researchers mostly improve the network structure, but rarely improve from the unstructured aspect. The loss function is an important part of the segmentation method based on deep learning. The improvement of the loss function can improve the segmentation effect of the network from the root, and the loss function is independent of the network structure, which can be used in various network models and segmentation tasks in plug and play. Starting from the difficulties in medical image segmentation, this paper first introduces the loss function and improvement strategies to solve the problems of sample imbalance, edge blur, false positive and false negative. Then the difficulties encountered in the improvement of the current loss function are analyzed. Finally, the future research directions are prospected. This paper provides a reference for the reasonable selection, improvement or innovation of loss function, and guides the direction for the follow-up research of loss function.

Compound Tinglizi Decoction intervenes COPD-associated pulmonary hypertension through regulation of HMGB1-mediated pyroptosis and immune imbalance / 中国中药杂志

This paper aimed to investigate the effects of high mobility group box 1(HMGB1)-mediated pulmonary artery smooth muscle cell pyroptosis and immune imbalance on chronic obstructive pulmonary disease-associated pulmonary hypertension(COPD-PH) in rats and the intervening mechanism of Compound Tinglizi Decoction. Ninety rats were randomly divided into a normal group, a model group, low-dose, medium-dose, and high-dose Compound Tinglizi Decoction groups, and a simvastatin group. The rat model of COPD-PH was established by fumigation combined with lipopolysaccharide(LPS) intravascular infusion, which lasted 60 days. Rats in the low, medium, and high-dose Compound Tinglizi Decoction groups were given 4.93, 9.87, and 19.74 g·kg~(-1) Compound Tinglizi Decoction by gavage, respectively. Rats in the simvastatin group were given 1.50 mg·kg~(-1) simvastatin by gavage. After 14 days, the lung function, mean pulmonary artery pressure, and arterial blood gas of rats were analyzed. Lung tissues of rats were collected for hematoxylin-eosin(HE) staining to observe the pathological changes. Real-time fluorescent quantitative polymerase chain reaction(qRT-PCR) was used to determine the expression of related mRNA in lung tissues, Western blot(WB) was used to determine the expression of related proteins in lung tissues, and enzyme linked immunosorbent assay(ELISA) was used to determine the levels of inflammatory factors in the lung tissues of rats. The ultrastructure of lung cells was observed by transmission electron microscope. The forced vital capacity(FVC), forced expiratory volume in 0.3 second(FEV_(0.3)), FEV_(0.3)/FVC, peek expiratory flow(PEF), respiratory dynamic compliance(Cdyn), arterial partial pressure of oxygen(PaO_2), and arterial oxygen saturation(SaO_2) were increased, and resistance of expiration(Re), mean pulmonary arterial pressure(mPAP), right ventricular hypertrophy index(RVHI), and arterial partial pressure of carbon dioxide(PaCO_2) were decreased by Compound Tinglizi Decoction in rats with COPD-PH. Compound Tinglizi Decoction inhibited the protein expression of HMGB1, receptor for advanced glycation end products(RAGE), pro caspase-8, cleaved caspase-8, and gasdermin D(GSDMD) in lung tissues of rats with COPD-PH, as well as the mRNA expression of HMGB1, RAGE, and caspase-8. Pulmonary artery smooth muscle cell pyroptosis was inhibited by Compound Tinglizi Decoction. Interferon-γ(IFN-γ) and interleukin-17(IL-17) were reduced, and interleukin-4(IL-4) and interleukin-10(IL-10) were incresead by Compound Tinglizi Decoction in lung tissues of rats with COPD-PH. In addition, the lesion degree of trachea, alveoli, and pulmonary artery in lung tissues of rats with COPD-PH was improved by Compound Tinglizi Decoction. Compound Tinglizi Decoction had dose-dependent effects. The lung function, pulmonary artery pressure, arterial blood gas, inflammation, trachea, alveoli, and pulmonary artery disease have been improved by Compound Tinglizi Decoction, and its mechanism is related to HMGB1-mediated pulmonary artery smooth muscle cell pyroptosis and helper T cell 1(Th1)/helper T cell 2(Th2), helper T cell 17(Th17)/regulatory T cell(Treg) imbalance.

Moonlighting and physician residents' compensation: is it all about money? A cross-sectional Brazilian study

ABSTRACT BACKGROUND: Moonlighting is a largely discussed, however under-explored, subject among physician residents. OBJECTIVES: To analyze the frequency of moonlighting and its related factors. DESIGN AND SETTING: This cross-sectional study enrolled medical residents from all geographical regions of Brazil. METHODS: A web-based structured closed-ended survey was applied that explored the frequency and type of moonlighting, residency programs characteristics, and psychological distress. The questionnaire was published on social networks. RESULTS: The completion rate was 71.4% (n = 1,419) and 37.7% were males aged 28.8 ± 3.2 (mean ± standard deviation) years, and 571 (40.2%) were post-graduate year (PGY) 1. There were residents from 50 medical specialties (the most common training area was clinical, 51.9%). A total of 80.6% practiced moonlighting, with an average weekly workload of 14.1 ± 9.4 h, usually overnight or in weekend shifts. Factors related to it were being PGY-2 or higher (adjusted odds ratio = 3.90 [95% confidence interval = 2.93-5.18], logistic regression), lower weekly residency duty hours (0.98 [0.97-0.99]), and a higher salary (1.23 [1.08-1.40]). In contrast, perception of a "fair/adequate" compensation was influenced by age (1.02 [1.01-1.02]), not being single (1.05 [1.01-1.10]), and residency duty hours (1.51 [1.22-1.88]). Depression, anxiety, diurnal somnolence scores, and work-personal life conflicts were not correlated with moonlighting status. CONCLUSION: Moonlighting frequency is high, and it is related to higher PGY, briefer residency duty hours, and the perception that remuneration should be higher. This study provides insights into the motivations for moonlighting and effort-reward imbalance.

O desequilíbrio esforço-recompensa está associado à hipertensão arterial entre servidores públicos brasileiros? Resultados do ELSA-Brasil / Is the effort-reward imbalance associated with hypertension among Brazilian civil servants? Results from the ELSA-Brasil study

Resumo Objetivos: analisar a associação entre o estresse no trabalho, segundo o modelo de desequilíbrio esforço-recompensa (DER), e a hipertensão arterial (HA), assim como investigar o papel modificador de efeito do excesso de comprometimento (EC) e do sexo. Métodos: análise seccional de dados de trabalhadores(as) ativos que participaram da segunda onda de coleta de dados (2012-2014) do Estudo Longitudinal de Saúde do Adulto (ELSA-Brasil). O estresse no trabalho foi mensurado pela versão brasileira da escala de DER, composta por três dimensões: esforço, recompensa e EC. A HA foi definida como níveis de pressão arterial sistólica/diastólica ≥ 140/90 mmHg ou uso de medicamento anti-hipertensivo. Empregou-se regressão logística, bruta e ajustada por potenciais fatores de confusão. As interações multiplicativas foram investigadas. Resultados: participaram 9.465 servidores, 51,9% do sexo feminino. A prevalência de HA foi de 34,9%. No modelo ajustado, associações limítrofes foram identificadas entre o DER (razão>1) e maior EC com maiores chances de HA (OR: 1,11; IC95%: 1,00; 1,24; e OR: 1,13; IC95%: 1,01; 1,26, respectivamente). A análise de interação indicou que sexo e EC não são modificadores de efeito. Conclusão: DER e EC associaram-se a maiores chances de HA, após ajuste. Sexo e EC não foram modificadores de efeito.

Abstract Objectives: to evaluate the association between job stress, according to the effort-reward imbalance (ERI) model, and hypertension (HTN), as well as to investigate the effect modifier role of overcommitment (OC) and sex. Methods: cross-sectional analysis of data from active workers who participated in the second data collection wave (2012-2014) of the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil). Job stress was measured by the ERI scale - Brazilian version, comprising three dimensions: effort, reward, and OC. HTN was defined as systolic or diastolic blood pressure levels ≥ 140/90 mmHg or antihypertensive medication use. Associations were estimated by logistic regression, crude and adjusted for potential confounding factors. Multiplicative interactions were investigated. Results: a total of 9,465 civil servants participated in the study, 51.9% females. HTN prevalence was 34.9%. The adjusted model identified borderline associations between ERI (ratio > 1) and higher OC with higher odds of HTN (OR = 1.11, 95%CI = 1.00; 1.24; and OR = 1.13; 95%CI = 1.01; 1.26, respectively). Interaction analysis indicated no differences in associations according to sex and OC. Conclusion: results show that ERI and OC are associated with higher odds of HTN after adjustment. Sex and OC were not effect modifiers.

Metabolic regulation of exogenous lactate on obese mice induced by high fat diet / 中国药科大学学报

@#This study investigates the metabolic regulatory effects of exogenous lactate on obesity mice induced by high-fat diet.We established obesity and metabolic disorder C57 mice model using a synthetic high-fat forage containing 60% fat.Some mice were fed with high-fat diet for 4 weeks to establish the model, being given 500 mg/(kg?d) lactate with ip for 4 weeks at the same time; the others were fed with high-fat diet for 8 weeks to establish the model, being given 500 mg/(kg?d) lactate 4 weeks after 4 weeks of modeling.During the trial period, the change of body weight and food intake, as well as serum glucose, lactate, triglycerides, insulin, and liver glycogen levels of both groups of mice were measured.Oral glucose tolerance test (OGTT) and insulin tolerance test (ITT) were used to assess glucose metabolism and insulin resistance in the body.At the end of the experiment, adipose tissue was dissected for weighing and histopathological examination.The expression of lipid synthesis and lipolysis genes in adipose tissue was detected by real-time PCR.The results showed that: (1) in the 4-week preventive medication trial, lactate had no significant effect on the body weight of normal and high-fat diet (HFD) mice, yet it increased the subcutaneous fat/visceral fat weight ratio; lactate could significantly reduce fasting blood glucose and liver glycogen levels in HFD mice while increasing blood lactate levels, significantly improving impaired glucose tolerance in HFD mice; lactate could improve the size and arrangement of adipocytes in the HFD group while significantly down-regulating the expression of fatty acid synthesis and lipolysis genes in adipose tissue; (2) in the 8-week treatment, both routes of lactate administration could partially reduce body weight in HFD group mice and reduce food intake, with the improvement trend for fat weight; both routes of lactate administration could significantly reduce fasting blood glucose levels in HFD mice, while significantly improving glucose and insulin tolerance, with some improvement of fasting insulin levels and insulin resistance index; both routes of lactate administration showed different degrees of improvement effect on adipocyte morphology in obese mice while significantly down-regulating lipolysis gene expression in adipose tissue.Therefore, for high-fat diet-induced obese mice with metabolic imbalance, exogenous lactate can stimulate glucose metabolism, inhibit adipose tissue lipolysis, and prevent adipocyte hypertrophy, thereby improving glucose tolerance and insulin sensitivity and reducing sugar-lipid metabolic disorder.

ADE signal mining and analysis of axitinib based on FAERS database / 中国药房

OBJECTIVE To provide references for the clinical safe use of axitinib. METHODS Adverse drug event （ADE） data for axitinib were collected from the US FDA Adverse Event Reporting System （FAERS） database from the first quarter of 2012 to the fourth quarter of 2022. The data were mined and analyzed by utilizing the ratio-of-reporting-ratio （ROR） method and comprehensive standard method of the United Kingdom’s Medicines and Healthcare Products Regulatory Agency （MHRA） of proportional imbalance measurement. RESULTS A total of 13 962 reports of axitinib-related ADEs were obtained， with patients’ age concentrated in 65-85 years （43.25%）， gender predominantly male （65.23%）， country of reporting predominantly US （60.01%）， and serious ADE outcomes mostly hospitalization or prolonged hospitalization （31.51%）. A total of 172 ADE risk signals were detected， involving 18 system and organ classifications （SOC）， mainly systemic diseases and various reactions at the site of administration （3 749 cases， 30.84%） and gastrointestinal system diseases （2 067 cases， 17.00%）. ADE risk signals that occurred more frequently were generally consistent with the drug instruction， such as diarrhea， fatigue， and hypertension； new ADE risk signals requiring clinical attention were death， immune-mediated nephritis， and PT signals contained in the SOC of various benign， malignant， and tumors of undetermined nature （including cysts and polyps）. CONCLUSIONS For ADEs that occur frequently with axitinib and are already contained in the drug instruction （e.g. hypertension， diarrhea）， they should be adequately evaluated before administration， especially for patients with combined use of immune checkpoint inhibitors and patients with underlying hypertension； for ADEs with stronger signals and newer ADEs （e. g. death， disease progression， tumor progression）， the patient’s disease progression should be closely monitored during the treatment period for potentially fatal ADEs； for its rare ADEs （e. g.immune-mediated nephritis， scrotal ulcer， non-infectious encephalitis）， clinical validation should be further strengthened.

Investigation on the pharmacological mechanisms of Shirebi granules in treating gouty arthritis with damp-heat syndrome based on crosstalk of Wnt/β-catenin signaling / 药学学报

Gouty arthritis is a type of metabolic rheumatic disease caused by autoimmune abnormalities. Currently, the use of Western medicine in the clinical treatment of gouty arthritis has been associated with a high risk of adverse reactions. Therefore, there is a growing interest in exploring therapeutic drugs from traditional Chinese medicine as a potential alternative. According to the theory of traditional Chinese medicine, gouty arthritis has been classified as damp-heat arthralgia syndrome. Shirebi granules has been found to have good clinical efficacy in treating gouty arthritis. However, its underlying pharmacological mechanisms remain unclear. To address this problem, the study first established the interaction network of candidate targets for Shirebi granules, which is used to treat damp-heat syndrome of gouty arthritis. Then, the key candidate targets of Shirebi granules for treating gouty arthritis with damp-heat syndrome were screened by calculating the topological features of the network nodes. Then, the functional mining of the key candidate targets revealed that the candidate targets of Shirebi granules may intervene in the biological process of inflammatory response and lipid metabolism through the crosstalk of Wnt/β-catenin signaling. To verify the effectiveness of Shirebi granules in treating gouty arthritis with damp-heat syndrome, a rat model was established. The results demonstrated that the granules significantly improved the severity of arthritis in rats with this condition, reduced joint inflammation, gait score, swelling index, increased mechanical pain threshold (P < 0.05), and reduced the content of serum inflammatory factors IL-1β, IL-6, and TNF-α in gouty arthritis rats with damp-heat syndrome (P < 0.01) gouty. It was also found that Shirebi granules effectively alleviated the symptoms of dampness heat syndrome such as local joint fever and dry mouth by reducing the temperature of the joints in acute gouty arthritis with damp-heat syndrome (AD) rats, increasing the threshold of heat pain, increasing water intake (P < 0.01), and inhibiting abnormal changes in the content of fatty acid oxidation related enzymes (P < 0.01). Western blot analysis showed that Shirebi granules increased the protein expression levels of Wnt and β-catenin (P < 0.01) while decreasing the protein expression of p65, p-p65 and PPARγ (P < 0.01) in rats with gouty arthritis and damp-heat syndrome. The results showed that Shirebi granules may reverse the "inflammation-immune" imbalance and lipid metabolism disorder by regulating the crosstalk of Wnt/β-catenin signaling, and play a role in alleviating the severity of the disease. This study provides a methodological reference for elucidating the pharmacological mechanisms of traditional Chinese medicine formulas. It also presents research ideas for the appropriate clinical use of Chinese patent medicines and the development of new clinical drugs for gouty arthritis therapy. The animal welfare and experiment procedures of this study were performed in accordance with the regulations of the Experimental Animal Ethics Committee of Experimental Research Center, China Academy of Chinese Medical Sciences (grant No. ERCCACMS11-2302-08).

The utilization of second sacral alar-iliac screw fixation technique in the treatment of adult spinal deformity: analysis of risk factors for postoperative sagittal imbalance / 中华骨科杂志

Objective:To evaluate the clinical outcomes and complications of second sacral alar-iliac (S 2AI) technique utilized in degenerative spinal deformity patients, and to analyze the potential risk factors for postoperative sagittal imbalance. Methods:From January 2014 to October 2020, a consecutive cohort of 39 degenerative spinal deformity patients who were treated with S 2AI were retrospectively reviewed, including 4 males and 35 females, aged 63.1±6.7 years (range, 43-73 years). All of the patients had a minimum of 2-year follow-up. According to the sagittal vertical axis (SVA) at the final follow-up, patients were divided into 2 groups. Sagittal balance group (SVA≤50 mm) and sagittal imbalance group (SVA>50 mm). Radiographic parameters including the Cobb's angle, coronal balance distance (CBD), thoracic kyphosis (TK), lumbar lordosis (LL), SVA, pelvic incidence (PI), pelvic tilt (PT) and sacral slope (SS) were measured in the standing radiographs before and after operation and at the latest follow up. Comparison was made between the two groups and the differences with statistical significance were analyzed with binary logistic regression analysis. Intraoperative and postoperative complications were recorded. The Scoliosis Research Society-22 (SRS-22) score were employed to evaluate the quality of life. Results:The average follow-up period was 30.3±9.1 months (range, 43-73 months). Eighteen patients (46%) were identified with sagittal imbalance at the last follow-up. Compared with the patients in the sagittal balance group, the preoperative SVA was significantly larger (83.1±56.2 mm vs. 48.1±51.1 mm, t=2.04, P=0.049) and the postoperative TK was significantly greater (27.8°±9.6° vs. 18.9°±13.4°, t=2.36, P=0.024) for patients in the sagittal imbalance group. Scores of pain domain (3.2±0.5 vs. 3.7±0.6) and self-image domain (3.4±0.8 vs. 3.8±0.6) in sagittal imbalance group were significantly lower than those of sagittal balance group ( P<0.05). Logistic regression analysis showed that larger preoperative SVA ( OR=1.02, P=0.028) and greater postoperative TK ( OR=1.09, P=0.022) were independent risk factors for the occurrence of sagittal imbalance during the follow-up periods. Conclusion:S 2AI screw fixation can achieve satisfying coronal deformity correction and great sagittal reconstruction after surgery in patients with degenerative spinal deformity. However, sagittal imbalance may still occur during the follow-up periods. Larger preoperative SVA and greater postoperative TK are independent risk factors for the occurrence of sagittal imbalance.

Crisis suprarrenal: prevención, corticoterapia y elección del fármaco, revisión de la evidencia actual y recomendaciones / Adrenal crisis: prevention, corticotherapy and choice of the drug, review of current evidence and recommendations

INTRODUCCIÓN. La crisis suprarrenal se refiere a la insuficiencia suprarrenal aguda; la cual es un trastorno en el que la corteza adrenal no produce suficientes hormonas esteroides (en especial cortisol) para satisfacer las demandas del cuerpo, de acuerdo al mecanismo fisiopatológico se la puede clasificar como primaria, secundaria y terciaria, siendo más común en pacientes con insuficiencia suprarrenal primaria. Es una emergencia potencialmente mortal que requiere tratamiento inmediato. OBJETIVO. Establecer una estrategia de prevención y tratamiento de la crisis suprarrenal, así como la farmacoterapia ideal y sus alternativas válidas. MATERIAL Y MÉTODOS. Se realizó una revisión bibliográfica en varias revistas virtuales de alto carácter científico como Cochrane Library, Cochrane Systematic Reviews Database, MEDLINE a través de PubMed y ClinicalTrial.gov. Se seleccionaron revisiones sistemáticas con o sin metaanálisis, ensayos clínicos y recomendaciones de expertos relacionados con prevención y tratamiento de crisis suprarrenal en general. RESULTADOS. Se obtuvieron 1819 resultados, de los cuales se seleccionaron 20 artículos con mayor validez y replicabilidad en el medio para establecer un protocolo unificado de actuación. CONCLUSIÓN. El objetivo de la terapia es el tratamiento de la hipotensión y reversión de las anomalías electrolíticas y de la deficiencia de cortisol. Se deben infundir por vía intravenosa grandes volúmenes (1 a 3 litros) de solución salina al 0,9% o dextrosa al 5% en solución salina al 0,9% y la administración de hidrocortisona (bolo de 100 mg), seguido de 50 mg cada 6 horas (o 200 mg / 24 horas como infusión continua durante las primeras 24 horas). Si no se dispone de hidrocortisona, las alternativas incluyen prednisolona, prednisona y dexametasona.

INTRODUCTION. Adrenal crisis refers to acute adrenal insufficiency; which is a disorder in which the adrenal cortex does not produce enough steroid hormones (especially cortisol) to meet the body's demands, according to the pathophysiological mechanism it can be classified as primary, secondary and tertiary, being more common in patients with primary adrenal insufficiency. It is a life-threatening emergency that requires immediate treatment. OBJECTIVE. To establish a strategy for the prevention and treatment of adrenal crisis, as well as the ideal pharmacotherapy and its valid alternatives. MATERIAL AND METHODS. A literature review was performed in several highly scientific virtual journals such as Cochrane Library, Cochrane Systematic Reviews Database, MEDLINE through PubMed and ClinicalTrial.gov. Systematic reviews with or without meta-analysis, clinical trials and expert recommendations related to prevention and treatment of adrenal crisis in general were selected. RESULTS. A total of 1819 results were obtained, from which 20 articles with greater validity and replicability in the setting were selected to establish a unified protocol for action. CONCLUSIONS. The aim of therapy is the treatment of hypotension and reversal of electrolyte abnormalities and cortisol deficiency. Large volumes (1 to 3 liters) of 0.9% saline or 5% dextrose in 0.9% saline and administration of hydrocortisone (100 mg bolus), followed by 50 mg every 6 hours (or 200 mg / 24 hours as a continuous infusion for the first 24 hours) should be infused intravenously. If hydrocortisone is not available, alternatives include prednisolone, prednisone, and dexamethasone.

Blood formed elements of the women with uterine tumors as one of the criterion for assessment of severity of the pathology

The indicators for structural analysis of blood formed elements are prominent in the assessment of pathologies, diagnostics and the degree. Therefore, we aimed to evaluate the ongoing alterations that reflect on the structural characteristics of blood formed elements based on the hormonal imbalance among menopausal women with uterine tumors. Blood samples from the women with benign (n=20), malignant (n=20) uterine tumors, and healthy menopausal women (control, n=20) were used. Enzyme-linked Immunosorbent assay (ELISA) kits were used for the quantitative determination of hormones. The blood formed elements ultrastructure observations were conducted using transmission electron microscope. Compared to control (33.8±0.7 pg/mL), estradiol level was higher in benign (45.7±0.9 pg/mL) and malignant (70.7±3.7 pg/mL) cases (P< 0.001). Similar pattern was noted in testosterone levels [control=0.38±0.03 ng/mL, benign=0.55±0.04 ng/mL (P< 0.01), malignant=1.56±0.14 ng/mL (P< 0.001)] was higher in malignant cases. In contrast, progesterone levels were decreased in the disease cases [control=0.93±0.05 ng/mL, benign=0.44±0.003 ng/mL, malignant=0.31±0.02 ng/ml (P< 0.001)]. Assessments of the morphologic structure of erythrocytes revealed pathological forms of erythrocytes (poikilocytosis) in case of benign, as well as in malignant tumors. particularly target cells (codocytes), hamlet cells, teardrop cells (dacrocytes), sickle cell (drepanocytes) erythrocytes. Using ELISA and transmission electron microscopy our results demonstrate that in case of malignant uterine tumor quantitative/structural changes occur in blood formed elements indicating ongoing alterations in hormonal imbalance. Assessing these changes in structural characteristics would be useful in examining uterine pathologies and subsequent treatment plans

Altered circulating adipokines and heart rate variability: A biomarker for autonomic imbalance in obese individuals

Background: Evidences indicate altered circulating adipokine levels in obesity could increase the risk for cardiovascular disease (CVD). Hence, it is crucial to determine cardiovascular health by assessing heart rate variability (HRV) and its association with circulating adipokines. Aim and Objectives: The aim of the study was to assess the adipokines level and its association with HRV in obese population. Materials and Methods: A cross-sectional comparative study was conducted on 45 obese (body mass index [BMI] > 25–29.9 kg/m2) and 45 non-obese (BMI: 18.5–22.9 kg/m2) age-gender-matched participants. Lead-II electrocardiogram was recorded and HRV parameters were obtained. Biochemical parameters, that is, fasting blood glucose, fasting insulin, HOMA-IR, lipid profile, leptin, and adiponectin levels were estimated. Group comparisons were done by independent student’s t-test, whereas the association between the parameters was done by Pearson’s correlation using SPSS 20v. P < 0.05 was considered statistically significant. Results: There was a significant increase in low frequency: high frequency (LF: HF) ratio (<0.001), fasting insulin (<0.001), HOMA-IR (<0.001), leptin (<0.001), Leptin-Adiponectin ratio (L/A ratio) (<0.001), total cholesterol (<0.001), triglycerides (<0.001), and low-density lipoproteins (<0.001), whereas significant decrease in total power (TP) of HRV (TP) (<0.001), adiponectin (<0.001), and high-density lipoproteins. A significant positive correlation between leptin, L/A ratio with LF: HF ratio (r = 0.793, P < 0.001) and a negative correlation with TP (–0.463, P < 0.001) was observed. Conclusion: Altered adipokines and its association with HRV in obese individuals could be an indicator of CVD. Hence, the current study suggests that the L/A ratio might be considered as a biomarker for cardiovascular health in obese individuals.

Zingerone alleviates cadmium-induced nephrotoxicity in rats via its antioxidant and anti-apoptotic properties

Objectives: Cadmium is an essential industrial metal and acts as an environmental toxicant that is a major cause of kidney diseases. Hence, we aimed to evaluate the possible nephroprotective effects of zingerone (ZGO), a major flavonoid constituent in ginger (Zingiber officinale) dry roots, against cadmium-induced nephrotoxicity in rats. Methods: In this study, Wistar albino rats [ACUC: HU2020/Z/FMS0120-01] were allocated randomly to 4 groups with seven animals in each group. The control group which received physiological saline; cadmium chloride (CdCl2) treatment group which received CdCl2 at a dose of 6.5 mg/kg intraperitoneally (i.p.) for 7 consecutive days; zingerone treatment group which received 25 mg/kg of zingerone orally for 7 consecutive days and CdCl2(6.5 mg/kg; i.p.)+ZGO (25 mg/kg; p.o.) treatment group which received CdCl2 and ZGO for 7 consecutive days. Results: Co-administration of ZGO along with CdCl2 resulted in a significant reduction in creatinine and urea levels of serum. Additionally, ZGO significantly diminished the tissue levels of Cd concentration, lipid peroxidation, and nitric oxide and significantly recovered the enzymatic and nonenzymatic antioxidant molecules, namely glutathione, total superoxide dismutase, catalase, and glutathione recycling enzymes peroxidase and reductase, in kidney tissue. Furthermore, ZGO treatment prevented the inflammation produced by CdCl2 by restraining the elevation in the level of pro-inflammatory cytokines (tumor necrosis factor-alpha and interleukin1beta). Moreover, ZGO improved histopathological alternations in the kidney by preventing apoptosis cascade in kidney tissue by stimulating Bcl-2 and suppressing Bax and caspase-3. Conclusions: Our findings suggest that ZGO has nephroprotective activity in cadmium-induced nephrotoxicity mostly via modulating of oxidant/antioxidant balance, inflammatory response, and apoptosis.