Metodología para incrementar la velocidad de reacción durante la defensa personal en cadetes

La preparación física, como parte del entrenamiento de los cadetes, busca poner en óptimo estado al practicante, perfecciona sus aptitudes naturales y desarrolla al máximo sus capacidades físicas por medio de ejercicios sistemáticos. En ese sentido, la velocidad de reacción durante la defensa personal constituye un importante aspecto a tratar; sin embargo, la observación y análisis de la realidad educativa en el Instituto de Enseñanza Superior del Ministerio del Interior, en Santiago de Cuba, reveló insuficiencias que limitan el logro de altos niveles en la velocidad de reacción. El objetivo del estudio consistió en elaborar una metodología para el desarrollo de la velocidad de reacción durante la defensa personal, en los cadetes de la carrera Ciencias de la Seguridad del Estado del Ministerio del Interior. En esa línea de pensamiento, se realizó una investigación con enfoque mixto y diseño cuasi experimental que empleó como métodos empíricos la revisión documental, la observación científica y la entrevista no estructurada; se utilizó la estadística inferencial por medio de la prueba de rangos de Wilcoxon para muestras relacionadas, lo que permitió conocer la eficiencia de los ejercicios especiales que se aplicaron. La calidad de la metodología quedó corroborada por los resultados obtenidos en la aplicación del criterio de expertos en la variante "Delphi" y del prexperimento, confirmados por diferentes técnicas estadísticas que resaltan la funcionalidad, sostenibilidad, pertinencia y factibilidad de la propuesta.

A preparação física, como parte do treinamento dos cadetes, busca colocar o praticante em ótimas condições, aperfeiçoar suas aptidões naturais e desenvolver ao máximo suas capacidades físicas por meio de exercícios sistemáticos. Nesse sentido, a velocidade de reação durante a defesa pessoal é um aspecto importante a ser abordado; no entanto, a observação e a análise da realidade educacional no Instituto de Ensino Superior do Ministério do Interior, em Santiago de Cuba, revelaram insuficiências que limitam a obtenção de altos níveis de velocidade de reação. O objetivo do estudo foi elaborar uma metodologia para o desenvolvimento da velocidade de reação durante a autodefesa, em cadetes do curso de Ciências de Segurança do Estado do Ministério do Interior. Nessa linha de pensamento, foi realizada uma pesquisa com abordagem mista e desenho quase experimental, utilizando como métodos empíricos a revisão documental, a observação científica e a entrevista não estruturada; foi utilizada a estatística inferencial por meio do teste de postos de Wilcoxon para amostras relacionadas, o que permitiu conhecer a eficiência dos exercícios especiais aplicados. A qualidade da metodologia foi corroborada pelos resultados obtidos na aplicação de critérios de especialistas na variante "Delphi" e no pré-experimento, confirmados por diferentes técnicas estatísticas que destacam a funcionalidade, a sustentabilidade, a relevância e a viabilidade da proposta.

Physical preparation, as part of training of the cadets, seeks to put the practitioner in optimal condition, perfects their natural aptitudes and develops their physical capabilities to the maximum through systematic exercises. In this sense, the speed of reaction during self-defense is an important aspect to address; however, the observation and analysis of the educational reality at the Institute of Higher Education of the Ministry of the Interior, in Santiago de Cuba, revealed insufficiencies that limit the achievement of high levels in reaction speed. The objective of the study was to develop a methodology for the development of reaction speed during self-defense, in the cadets of the State Security Sciences career of the Ministry of the Interior. In this line of thought, research was carried out with a mixed approach and quasi-experimental design that used documentary review, scientific observation and unstructured interviews as empirical methods; inferential statistics was used through the Wilcoxon rank test for related samples, which made it possible to know the efficiency of the special exercises that were applied. The quality of the methodology was corroborated by the results obtained in the application of expert criteria in the "Delphi" variant and of the pre-experiment, confirmed by different statistical techniques that highlight the functionality, sustainability, relevance and feasibility of the proposal.

Complicaciones perianales causadas por agentes modeladores inyectados en glúteos / Perianal complications caused by gluteal injection of modeling agents

En este reporte presentamos tres pacientes en quienes ocurrieron condiciones inflamatorias perianales tardías, luego de la administración de sustancias modeladoras no identificadas en los glúteos. El diagnóstico inicial y supuesto no fue correcto, ya que no se investigó durante la evaluación preliminar el antecedente de la administración de elementos modeladores. Recomendamos que los pacientes con patologías inflamatorias del ano, sobre todo aquellos cuyo curso es extraño, se les pregunte acerca de la administración de agentes modeladores en los glúteos. Esta práctica puede contribuir a la eficacia del diagnóstico de manifestaciones perianales caracterizadas por flogosis, que se presentan de forma inusual. (AU)

In this report we present three patients in which late perianal inflammatory conditions occurred after administration of unidentified modeling agents to the buttocks. The initial diagnosis was not correct because of the administration of modeling agents was not investigated during the initial eval-uation. We recommend inquiring patients with inflammatory pathologies of the anus, especially those whose course is unusual, about the adminis-tration of modeling agents to the buttocks. This approach can contribute to the efficiency of the diagnosis of perianal complaints characterized by inflammation, but rare in its appearance. (AU)

Safety of a 90-min duration of intravenous infusion of obinutuzumab in patients with B-cell non-Hodgkin's lymphoma in a tertiary hospital in China: a prospective, open-label, exploratory clinical trial

This study aimed to analyze the safety and applicability of a 90-min duration of infusion (SDI) of obinutuzumab in patients with B-cell non-Hodgkin's lymphoma (NHL) in a tertiary hospital in China. This exploratory clinical trial was performed at Jiangsu Province Hospital. All patients were treated with the standard infusion regimen for the first infusion. If no grade ≥3 infusion-related reactions (IRRs) occurred, the subsequent infusions were given as SDI. The primary endpoint was the incidence of IRR during the standard infusion (3-4 h) and 90-min SDI regimens. This study enrolled 208 patients and all completed cycle 1. Forty-one patients (19.71%) had IRRs: five (2.40%) with grade 1, twenty-eight (13.46%) with grade 2, and eight (3.85%) with grade 3. The 41 patients had 71 IRRs, mainly fever (40.85%), chest pain/tightness (12.68%), and dyspnea (9.86%). The occurrence of IRRs in the first infusion was significantly lower in patients who received oral acetaminophen prophylaxis than those who did not (10.72% vs 30.21%, P<0.001). For the subsequent cycles with 90-min SDI, only two (0.25%) IRRs occurred among 814 infusions (one grade 1 hand numbness and one grade 2 chill/fever). The 90-min obinutuzumab SDI might be safe and feasible in patients with B-cell NHL in China.

Clinico-pathological assessment of virulent Newcastle Disease Virus in ducks / Avaliação clínico-patológica do Vírus da Doença de Newcastle em patos

Abstract Newcastle disease (ND) is an infectious, highly contagious and lethal disease of avian species. It is considered that ducks are natural reservoir or carrier for Newcastle disease virus (NDV) and are resistant against different strains of NDV. Current study was designed to evaluate the pathogenesis of Newcastle disease in domestic ducks through histopathology, immunohistochemistry (IHC) and serum biochemical changes. For this purpose, eighty ducks were reared for 42 days and divided in two groups A and B. Ducks in group A were challenged with (NDV) at rate of 0.1 ml of ELD50 (virus titer 107.32/100µl) on second week of age, whereas Group B was control negative. Splenomegaly, atrophy of thymus and necrotic lesion in kidney were observed on 9th day of post infection. Hepatic degeneration and mononuclear cell infiltration were noticed in proventriculus and intestine in challenged ducks. Viral antigen detected in lungs, intestine, proventriculus and lymphoid organs of infected ducks through IHC. Albumin and total protein values were significantly low in infected groups A as compared to control group B. ALT, AST, and ALP values were significantly high in infected group A. On 5th and 7th day of post infection oropharyngeal swabs were negative for NDV and cloacal swabs were positive for NDV through Reverse transcriptase polymerase chain reaction. It is concluded that ducks are susceptible to NDV and virulent strain of NDV caused disease in ducks.

Resumo A doença de Newcastle (DN) é uma doença infecciosa, altamente contagiosa e letal de espécies aviárias. Considera-se que os patos são reservatórios ou portadores naturais do vírus da doença de Newcastle (VDN) e são resistentes a diferentes cepas de VDN. O presente estudo foi desenvolvido para avaliar a patogênese da DN em patos domésticos por meio de histopatologia, imuno-histoquímica (IHQ) e alterações bioquímicas séricas. Para este propósito, 80 patos foram criados por 42 dias e divididos em dois grupos A e B. Os patos do grupo A foram submetidos ao VDN a uma taxa de 0,1 ml de ELD50 (título viral de 107,32 / 100 µl) na segunda semana de idade, enquanto o Grupo B foi controle negativo. Esplenomegalia, atrofia do timo e lesão necrótica no rim foram observadas no 9º dia pós-infecção. Degeneração hepática e infiltração de células mononucleares foram observadas no proventrículo e intestino em patos infectados. Antígeno viral foi detectado em pulmões, intestino, proventrículo e órgãos linfoides de patos infectados por IHQ. Os valores de albumina e proteína total foram significativamente baixos no grupo A infectado em comparação com o grupo B. Os valores de ALT, AST e ALP foram significativamente altos no grupo A. No 5º e no 7º dia após a infecção, os esfregaços orofaríngeos foram negativos para VDN, enquanto os esfregaços cloacais foram positivos para VDN por meio da reação em cadeia da polimerase via transcriptase reversa. Conclui-se que os patos são suscetíveis ao VDN e à cepa virulenta de VDN que causou doenças em patos.

Total Saponins in Paridis Rhizoma： A Review / 中国实验方剂学杂志

Paridis Rhizoma possesses the functions of clearing heat and detoxifying， alleviating swelling and relieving pain， cooling the liver and calming the convulsion. Saponins are the main active components of Paridis Rhizoma. Studies have shown that total saponins in Paridis Rhizoma have obvious inhibitory effect on solid tumors such as breast cancer， lung cancer， gastric cancer， and liver cancer and non-solid tumors such as leukemia. The saponins may exert the anti-tumor effects by inhibiting the proliferation， migration， and invasion of tumor cells， regulating cell cycle， inducing apoptotic and non-apoptotic death pathways， and regulating metabolism and tumor microenvironment. Furthermore， total saponins in Paridis Rhizoma showed anti-inflammatory， antioxidant， antimicrobial， hemostatic， and uterus-contracting activities. At the same time， they may induce apoptosis of normal cells， inflammation and oxidative stress， and metabolic disorders. In recent years， the reports of liver injury， reproductive injury， gastrointestinal injury， hemolysis， and other adverse reactions caused by total saponins in Paridis Rhizoma have been increasing. Pharmacokinetic studies have shown that there are significant differences in the metabolism of total saponins in Paridis Rhizoma administrated in different ways. Injection has a fast clearance rate， while oral administration may have hepatoenteric circulation. Meanwhile， due to the low solubility and activation of P-glycoprotein （P-gp） molecular pump， the prototype absorption， intestinal permeability， and recovery rate of total saponins in Paridis Rhizoma are poor， which affects the bioavailability. The bioavailability can be improved to some extent by preparing new dosage forms or new drug delivery systems with advanced technology. This paper reviews the pharmacological effect， pharmacokinetics， and adverse reactions of Rhizoma Paridis total saponins by searching the China National Knowledge Infrastructure （CNKI）， VIP， and Web of Science with ''Rhizoma Paridis total saponins'' as the keywords， hoping to provide references for the research， development， and clinical application of such components.

Transcriptomic Analysis of Wuzi Yanzongwan on Testicular Spermatogenic Function in Semi-castrated Male Mice / 中国实验方剂学杂志

ObjectiveTo screen out the transcriptomes related to the intervention of Wuzi Yanzongwan on the spermatogenic function of semi-castrated male mice， and to explore its potential mechanism in the intervention of the progress of low spermatogenic function. MethodBalb/c mice were randomly divided into sham-operated group， model group， testosterone propionate group（0.2 mg·kg-1·d-1， intramuscular injection） and Wuzi Yanzongwan group（1.56 g·kg-1·d-1， intragastric administration） according to body weight， with 12 mice in each group. The right testicle and epididymis were extracted from the model group and the drug administration group to construct the semi-castrated model of low spermatogenic function， while the fur and the right scrotum of the sham-operated group were only cut and immediately sterilized and sutured. At the end of the intervention， hematoxylin-eosin（HE） staining was used to observe the histopathology of testis， enzyme-linked immunosorbent assay（ELISA） was used to detect the levels of serum testosterone（T）， luteinizing hormone（LH） and follicle stimulating hormone（FSH）. The sperm count and motility of epididymis were measured by automatic sperm detector of small animal. Transcriptomic microarray technology was used to detect the mRNA expression level of testicular tissue in each group， the transcriptome of genes related to the regulation of Wuzi Yanzongwan was screened， and three mRNAs were selected for Real-time fluorescence quantitative polymerase chain reaction（Real-time PCR） to verify the transcriptome data. Through the annotation analysis of Gene Ontology（GO） and the signaling pathway analysis of Kyoto Encyclopedia of Genes and Genomes（KEGG）， the related functions of drugs regulating transcriptome were analyzed. ResultCompared with the sham-operated group， the testicular tissue of mice in the model group showed spermatogenic injury， contraction and vacuolization of the seminiferous tubules， reduction of spermatogenic cells at all levels， widening of the interstitial space， obstruction of spermatogonial cell development and other morphological abnormalities， and serum T significantly decreased， LH significantly increased（P<0.01）， and FSH elevated but no statistically significant difference， the count and vitality of epididymal sperm significantly decreased（P<0.01）. There were 882 differentially expressed mRNAs in the testicular tissues， of which 565 were up-regulated and 317 were down-regulated. Cluster analysis showed that these differentially expressed mRNA could effectively distinguish between the sham-operated group and the model group. Compared with the model group， the damage to testicular tissue in the Wuzi Yanzongwan group was reduced， the structure of the seminiferous tubules was intact， vacuolization was reduced， and the number of spermatogenic cells at all levels was significantly increased and arranged tightly. The serum T significantly increased， LH significantly decreased（P<0.01）， and FSH decreased but the difference was not statistically significant. The count and vitality of sperm in the epididymis were significantly increased（P<0.01）. Moreover， Wuzi Yanzongwan could regulate 159 mRNA levels in the testes of semi-castrated mice， of which 32 were up-regulated and 127 were down-regulated， and the data of the transcriptome assay was verified to be reliable by Real-time PCR. GO and KEGG analysis showed that the transcriptome functions regulated by Wuzi Yanzongwan were involved in the whole cell cycle process of sperm development such as sex hormone production of interstitial cells in testis， renewal， differentiation， metabolism， apoptosis and signal transduction of spermatogenic cells， and were closely related to the biological behaviors of signaling pathways such as spermatogenic stem cell function， endoplasmic reticulum protein processing and metabolic program. ConclusionWuzi Yanzongwan can effectively improve the low spermatogenic function of semi-castrated male mice， and its mechanism may be related to the regulation of testicular transcriptional regulatory network， the synthesis of sex hormones in testicular interstitial cells， the function of spermatogenic stem cells， the whole cell cycle process of spermatogenesis， as well as the expression of endoplasmic reticulum protein processing and metabolic program related genes transcription.

Establishment and validation of nomogram prediction model of cefoperazone/sulbactam-induced thrombocytopenia / 中国药房

OBJECTIVE To explore the predictive factors of cefoperazone/sulbactam-induced thrombocytopenia in adult inpatients， and to establish and validate the nomogram prediction model. METHODS Data of adult inpatients treated with cefoperazone/sulbactam in Xi’an Central Hospital from Jun. 30th， 2021 to Jun. 30th， 2023 were retrospectively collected. The training set and internal validation set were randomly constructed in a 7∶3 ratio. Singler factor and multifactor Logistic regression analysis were used to screen the independent predictors of cefoperazone/sulbactam-induced thrombocytopenia. The nomogram was drawn by using “RMS” of R 4.0.3 software， and the predictive performance of the model was evaluated by the receiver operating characteristic curve and C-index curve. Hosmer-Lemeshow goodness-of-fit test was used to evaluate the calibration degree of the model. Using the same standard， the clinical data of hospitalized patients receiving cefoperazone/sulbactam in Xi’an First Hospital in the same period were collected for external validation of the nomogram prediction model. RESULTS A total of 1 045 patients in Xi’an Central Hospital were included in this study， among which 67 patients suffered from cefoperazone/sulbactam-induced thrombocytopenia， with an incidence of 6.41%. After the false positive patients were excluded， 473 patients were included finally， including 331 in the training set and 142 in theinternal validation set. Multifactor Logistic regression analysis showed that age [OR＝1.043， 95%CI （1.017， 1.070）]， estimated glomerular filtration rate （eGFR） [OR＝0.988，95%CI（0.977， 0.998）]， baseline platelet （PLT） [OR＝0.989， 95%CI（0.982， 0.996）]， nutritional risk [OR＝3.863， 95%CI（1.884， 7.921）] and cumulative defined daily doses （DDDs） [OR＝1.082， 95%CI（1.020， 1.147）] were independent predictors for cefoperazone/sulbactam-induced thrombocytopenia （P＜0.05）. The C-index values of the training set and the internal validation set were 0.824 [95%CI （0.759， 0.890）] and 0.828 [95%CI （0.749， 0.933）]， respectively. The results of the Hosmer-Lemeshow test showed that χ 2 values were 0.441 （P＝0.802） and 1.804 （P＝0.406）. In the external validation set， the C-index value was 0.808 [95%CI （0.672， 0.945）]， the χ 2 value of the Hosmer-Lemeshow test was 0.899 （P＝0.638）. CONCLUSIONS The independent predictors of cefoperazone/sulbactam-induced thrombocytopenia include age， baseline PLT， eGFR， nutritional risk and cumulative DDDs. The model has good predictive efficacy and extrapolation ability， which can help clinic identify the potential risk of cefoperazone/sulbactam-induced thrombocytopenia quickly and accurately.

Ameliorative effect and mechanism of curcumin on diabetes model rats with depression / 中国药房

OBJECTIVE To study the ameliorative effect and potential mechanism of curcumin on diabetes model rats with depression based on cAMP response element binding protein （CREB）/brain-derived neurotrophic factor （BDNF） signaling pathway. METHODS The diabetes model rat with depression was established by high fat and high sugar diet+intraperitoneal injection of streptozotocin+chronic unpredictable stress-induced depression. The successfully modeled rats were randomly divided into model group， positive control group （0.18 g/kg metformin and 1.8 mg/kg fluoxetine， gavage）， curcumin low-dose and high-dose groups （30， 60 mg/kg， gavage） and curcumin high-dose+CREB inhibitor group [60 mg/kg curcumin （gavage）+5 mg/kg CREB inhibitor 666-15 （intraperitoneal injection）]， with 12 rats in each group. Another 12 healthy rats were selected as the normal group. Each group was given a corresponding intervention for 4 weeks， the fasting blood glucose level of rats was detected， and the depression of rats was assessed. The levels of corticosterone （CORT） and inflammatory factors [tumor necrosis factor-α （TNF-α）， interleukin- 1β （IL-1β）， IL-6] in serum， and the levels of norepinephrine （NE） and 5-hydroxytryptamine （5-HT） in hippocampal tissue were determined. The pathological changes and neuronal apoptosis were observed in the hippocampal tissue of rats in each group； the expression levels of CREB， BDNF mRNA and protein in hippocampal tissue were detected. RESULTS Compared with the normal group， the hippocampal tissue of rats in the model group was severely damaged， and neurons were scattered， while the fasting blood glucose， the forced swimming immobility time， the tail suspension immobility time， serum levels of CORT， TNF-α， IL-1β and IL-6， and neuron apoptosis indexes were all increased or prolonged significantly （P＜0.05）. The levels of NE and 5-HT， the number of surviving neurons， and the expression levels of CREB and BDNF mRNA and protein in hippocampal tissue were decreased significantly （P＜0.05）. Compared with the 的model group， the damage to hippocampal tissue was relieved in the positive control group and curcumin groups， while the above indexes were improved significantly （P＜0.05）. The improvement effect of curcumin high-dose group was better than that of curcumin low-dose group （P＜0.05）. CREB inhibitor could significantly reverse the ameliorative effect of high-dose curcumin on the model rats （P＜0.05）. CONCLUSIONS Curcumin can improve the depression of diabetes model rats with depression， and relieve neuronal damage and inflammatory response， the mechanism of which may be associated with activating CREB/BDNF signaling pathway.

Study on the potential allergen and mechanism of pseudo-allergic reactions induced by combined using of Reduning injection and penicillin G injection based on metabolomics and bioinformatics / 药学学报

Based on the strategy of metabolomics combined with bioinformatics, this study analyzed the potential allergens and mechanism of pseudo-allergic reactions (PARs) induced by the combined use of Reduning injection and penicillin G injection. All animal experiments and welfare are in accordance with the requirements of the First Affiliated Experimental Animal Ethics and Animal Welfare Committee of Henan University of Chinese Medicine (approval number: YFYDW2020002). Based on UPLC-Q-TOF/MS technology combined with UNIFI software, a total of 21 compounds were identified in Reduning and penicillin G mixed injection. Based on molecular docking technology, 10 potential allergens with strong binding activity to MrgprX2 agonist sites were further screened. Metabolomics analysis using UPLC-Q-TOF/MS technology revealed that 34 differential metabolites such as arachidonic acid, phosphatidylcholine, phosphatidylserine, prostaglandins, and leukotrienes were endogenous differential metabolites of PARs caused by combined use of Reduning injection and penicillin G injection. Through the analysis of the "potential allergen-target-endogenous differential metabolite" interaction network, the chlorogenic acids (such as chlorogenic acid, neochlorogenic acid, cryptochlorogenic acid, and isochlorogenic acid A) and β-lactam allergens in the combination of the two may be mainly regulated by PLD1, PLA2G12A and CYP1A1. The three upstream signal target proteins mainly activate the arachidonic acid metabolic pathway, promote the degranulation of mast cells, release downstream endogenous inflammatory mediators, and induce PARs.

The attenuating and potentiating effects of traditional Chinese medicine in immune checkpoint therapy / 中国临床药理学与治疗学

Immunotherapy has become a global focus in cancer clinical practice and scientific research. In the past two years, PD-1\PD-L1 and CTLA-4 inhibitors, especially Nivolumab, Pembrolizumab, Atezolizumab and Lpilimumab, have been used in non-small cell lung cancer, colon cancer. Promising results have been obtained in malignancies such as melanoma and urinary tract cancer. Traditional Chinese medicine has a long history in China. Modulating immune checkpoints has certain advantages in treating malignant tumors, and it has shown good efficacy in improving its adverse events. This article reviews the role of traditional Chinese medicine in regulating immune checkpoints and improving adverse reactions and its application prospects in immunomodulatory treatment.

Outbreak investigation of a campus bacterial dysentery by water source pollution in Lhasa City / 中国学校卫生

Objective@#To investigate risk factors and the nature of the outbreak of bacillary dysentery in Lhasa City, so as to customize targeted prevention and control measures.@*Methods@#Using on site epidemiological investigation, the suspected, probable and confirmed cases of bacillary dysentery in one school and one kindergarten in Lhasa City from June 26 to July 1, 2022 were collected, and additional cases were identified through interview from school staffs and family members, reviewing morning examination records and tracking records of school illness related absence. A case control study was conducted to investigate suspicious meals and drinking raw water, and polymerase chain reaction (PCR) was performed to detect Shigella line nucleic acid fragment in the patients feces, anal swabs, retained food, and terminal water.@*Results@#A total of 55 cases were found in two schools, with the prevalence rate of 15.41% in total and 16.71% in students ( n =53), 7.5% in staff ( n =2). The epidemic curve was suggestive of a point source exposure. The prevalence rate among students who walk to school and students who live in the school showed no difference (16.10%，17.09%)( χ 2=0.05, P >0.05), and the prevalence rate was higher among elementary school students than kindergarten students (19.83%，6.67%)( χ 2=7.13, P <0.05). Case control comparisons showed a direct association between drinking raw water and morbidity in the case and control groups during June 24-26 ( OR=4.01, 95%CI =1.75-9.19, P < 0.05). A total of 23 fecal Shigella nucleic acid positives were detected from the two schools, two from the end water in front of the cafeteria door, and two from sludge in the sewage pipe around the wellhead.@*Conclusions@#The outbreak of bacillary dysentery is caused by the contamination of the pipe network water. Health administrative departments should improve the supervision and management of drinking water health safety, and schools should strengthen the management of water supply facilities for effectively prevent of waterborne infectious disease outbreaks.

Case analysis of a patient with isavuconazonium-caused pancytopenia / 中国药房

OBJECTIVE To correctly identify and deal with the adverse drug reaction as pancytopenia caused by isavuconazonium and to provide reference for the safe use of isavuconazonium. METHODS Clinical pharmacists analyzed a case of severe infection and renal insufficiency who experienced pancytopenia after using isavuconazonium. Clinical pharmacists screened the drugs used during hospitalization and evaluated the relationship between this adverse drug reaction and isavuconazonium， as well as the possible mechanisms， based on the half-life of the drugs and relevant literature. RESULTS & CONCLUSIONS The relationship between pancytopenia and isavuconazonium was assessed as “possibly related”. When using isavuconazonium， attention should be paid to avoiding the combination of drugs with the same mechanism or potential interaction. For patients who have a course of treatment for more than 2 weeks， have hematological abnormalities or complicated with liver and renal insufficiency， or should use it combined with other drug with same mechanism， it may be considered to increase the frequency of blood routine monitoring.

Rare and severe adverse reaction diabetic ketoacidosis induced by bevacizumab：one case report / 中国药房

OBJECTIVE To provide reference for the safe use of bevacizumab in cancer patients. METHODS The diagnosis and treatment of a 65-year-old female lung adenocarcinoma patient with diabetic ketoacidosis （DKA） induced by bevacizumab was retrospectively analyzed， and the possible mechanisms and causes were analyzed based on literature review. RESULTS & CONCLUSIONS The diagnosis and treatment process of patients were analyzed， and DKA caused by other drugs and disease factors were excluded. DKA was considered to be caused by the use of bevacizumab according to Naranjo’s ADR evaluation scale； the acidosis of the patient improved rapidly after one hemodialysis treatment. DKA caused by bevacizumab is rare in clinic， clinicians should be aware that bevacizumab may affect pancreatic function and induce DKA， and early detection and treatment should be achieved to improve the prognosis.

Renal injury caused by tenofovir disoproxil fumarate in a patient with liver cancer complicated with HBV infection：a case report and literature analysis / 中国药房

Tenofovir disoproxil fumarate （TDF） is a first-line treatment for chronic hepatitis B. With increasing use worldwide， the adverse events of renal injury caused by this drug have also attracted industry attention. This article reports a 61- year-old patient with liver cancer complicated with hepatitis B virus （HBV） infection. The patient started using TDF in mid-March 2022 and developed kidney injury after 2 months of treatment， during which he received 2 courses of donafenib combined with sintilimab chemotherapy and irregular administration of diclofenac for pain relief. In this paper， Naranjo’s assessment scale was used to evaluate the drugs that may be associated with renal injury， including TDF and sintilimab， and the drugs that are suspected to be associated with renal injury are donafenib and diclofenac. The renal injury caused by TDF can be judged according to the changes in the patient’s condition， the incidence of drug-induced renal injury， clinical manifestations， occurrence time， occurrence mechanism， drug combination， and high-risk factors. The changes of serum creatinine in patients with liver cancer complicated with HBV infection after TDF should be dynamically monitored in the clinic， and the dose of antiviral drugs should be adjusted if necessary and other antiviral drugs with less impact on renal function can be selected， to provide individualized medication recommendations for tumor patients， reduce the incidence of TDF-related renal injury.

Significance of high-sensitivity polymerase chain reaction in detecting hepatitis B virus in chronic hepatitis B patients with a very low viral load / 临床肝胆病杂志

ObjectiveTo investigate the significance of high-sensitive polymerase chain reaction （PCR） in detecting hepatitis B virus （HBV） among the population with a very low viral load （HBV DNA 10‍ — ‍99 IU/mL）. MethodsThis study was conducted among the chronic hepatitis B （CHB） patients who were treated with nucleos（t）ide analogues for ≥48 weeks in The Fifth Affiliated Hospital of Guangzhou Medical University from September 2019 to February 2022 and had an HBV DNA load below the lower limit of ordinary-sensitivity detection （100 IU/mL）. Then high-sensitivity HBV DNA detection was performed for all patients， and according to these results， the patients were divided into very low viral load group （VLVL group with an HBV DNA load of 10‍ — ‍99 IU/mL） and complete virologic response group （CVR group with an HBV DNA load of <10 IU/mL or without HBV DNA detected）. The two groups were compared in terms of general characteristics， serum virological indicators， biochemical parameters， and noninvasive fibrosis markers； the value of related serum virological indicators in predicting the results of high-sensitivity HBV DNA above the lower limit of detection were assessed； the influencing factors for failure to achieve CVR were analyzed. The independent-samples t test was used for comparison of normally distributed continuous data between two groups， and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups； the chi-square test or the Fisher’s exact test was used for comparison of categorical data between two groups. The receiver operating characteristic （ROC） curve was used to investigate the value of related serum virological indicators in predicting the results of high-sensitivity HBV DNA above the lower limit of detection， and a binary logistic regression analysis was used to investigate the influencing factors for failure to achieve CVR. ResultsA total of 106 CHB patients were enrolled， with 24 in the VLVL group and 82 in the CVR group. Compared with the CVR group， the VLVL group had a significantly younger age （P=0.004） and significantly higher quantitative hepatitis B surface antigen （qHBsAg） level （P=0.002）， HBeAg positive rate （P=0.002）， pgRNA positive rate （P=0.010）， and alanine aminotransferase level （P=0.017）. The qHBsAg level had an area under the ROC curve of 0.717 （P=0.002） in predicting the results of high-sensitivity HBV DNA above the lower limit of detection （>10 IU/mL）， with an optimal cut-off value of 1 214.5 IU/mL， a sensitivity of 95.5%， and a specificity of 53.9%. Positive HBeAg （odds ratio ［OR］=3.654， 95% confidence interval ［CI］： 1.162‍ —‍ ‍11.489， P=0.027） and qHBsAg （OR=2.985， 95%CI： 1.058‍ — ‍8.422， P=0.039） were independent influencing factors for failure to achieve CVR. ConclusionSome CHB patients have an HBV DNA load of <100 IU/mL by ordinary-sensitivity detection， but with the presence of VLVL determined by high-sensitivity PCR. The VLVL group had significantly higher level of inflammatory damage and positive rates of pgRNA and HBeAg. Positive HBeAg and high qHBsAg level are independent influencing factors for failure to achieve CVR. Clinicians should not ignore the presence of VLVL in CHB patients， and high-sensitivity HBV DNA detection should be performed in a timely manner.

Application of metagenomic next-generation sequencing in prevention and control of infection in solid organ transplantation / 器官移植

Organ transplantation has become an effective treatment for multiple end-stage diseases. However, the recipients of organ transplantation need to take immunosuppressive drugs for a long time after operation, which leads to low immune function and relatively high incidence of bacterial, viral and fungal infections. Traditional microbial detection methods, such as pathogen culture, immunological detection and polymerase chain reaction, have been widely applied in infection detection, whereas these methods may cause problems, such as long detection time and presumed pathogens. Metagenomic next-generation sequencing has been widely adopted in infection prevention and control in organ transplantation in recent years due to high detection rate and comprehensive detection of pathogen spectrum. In this article, the application of metagenomic next-generation sequencing in the prevention and control of infection in solid organ transplantation was reviewed, aiming to provide reference for the diagnosis and treatment of transplantation-related infection.

Self-sufficient nanoparticles with dual-enzyme activity trigger radical storms and activate cascade-amplified antitumor immunologic responses

Radiotherapy (RT) can potentially induce systemic immune responses by initiating immunogenic cell death (ICD) of tumor cells. However, RT-induced antitumor immunologic responses are sporadic and insufficient against cancer metastases. Herein, we construct multifunctional self-sufficient nanoparticles (MARS) with dual-enzyme activity (GOx and peroxidase-like) to trigger radical storms and activate the cascade-amplified systemic immune responses to suppress both local tumors and metastatic relapse. In addition to limiting the Warburg effect to actualize starvation therapy, MARS catalyzes glucose to produce hydrogen peroxide (H2O2), which is then used in the Cu+-mediated Fenton-like reaction and RT sensitization. RT and chemodynamic therapy produce reactive oxygen species in the form of radical storms, which have a robust ICD impact on mobilizing the immune system. Thus, when MARS is combined with RT, potent systemic antitumor immunity can be generated by activating antigen-presenting cells, promoting dendritic cells maturation, increasing the infiltration of cytotoxic T lymphocytes, and reprogramming the immunosuppressive tumor microenvironment. Furthermore, the synergistic therapy of RT and MARS effectively suppresses local tumor growth, increases mouse longevity, and results in a 90% reduction in lung metastasis and postoperative recurrence. Overall, we provide a viable approach to treating cancer by inducing radical storms and activating cascade-amplified systemic immunity.

Chuanxiong Rhizoma extracts prevent liver fibrosis via targeting CTCF-c-MYC-H19 pathway / 中草药·英文版

OBJECTIVE@#Hepatic fibrosis has been widely considered as a conjoint consequence of almost all chronic liver diseases. Chuanxiong Rhizoma (Chuanxiong in Chinese, CX) is a traditional Chinese herbal product to prevent cerebrovascular, gynecologic and hepatic diseases. Our previous study found that CX extracts significantly reduced collagen contraction force of hepatic stellate cells (HSCs). Here, this study aimed to compare the protection of different CX extracts on bile duct ligation (BDL)-induced liver fibrosis and investigate plausible underlying mechanisms.@*METHODS@#The active compounds of CX extracts were identified by high performance liquid chromatography (HPLC). Network pharmacology was used to determine potential targets of CX against hepatic fibrosis. Bile duct hyperplasia and liver fibrosis were evaluated by serologic testing and histopathological evaluation. The expression of targets of interest was determined by quantitative real-time PCR (qPCR) and Western blot.@*RESULTS@#Different CX extracts were identified by tetramethylpyrazine, ferulic acid and senkyunolide A. Based on the network pharmacological analysis, 42 overlap targets were obtained via merging the candidates targets of CX and liver fibrosis. Different aqueous, alkaloid and phthalide extracts of CX (CXAE, CXAL and CXPHL) significantly inhibited diffuse severe bile duct hyperplasia and thus suppressed hepatic fibrosis by decreasing CCCTC binding factor (CTCF)-c-MYC-long non-coding RNA H19 (H19) pathway in the BDL-induced mouse model. Meanwhile, CX extracts, especially CXAL and CXPHL also suppressed CTCF-c-MYC-H19 pathway and inhibited ductular reaction in cholangiocytes stimulated with taurocholate acid (TCA), lithocholic acid (LCA) and transforming growth factor beta (TGF-β), as illustrated by decreased bile duct proliferation markers.@*CONCLUSION@#Our data supported that different CX extracts, especially CXAL and CXPHL significantly alleviated hepatic fibrosis and bile duct hyperplasia via inhibiting CTCF-c-MYC-H19 pathway, providing novel insights into the anti-fibrotic mechanism of CX.

Clinical Characteristics and Potential Risk Factors Analysis of Liver Injury Related to Epimedii Folium Preparation / 中国实验方剂学杂志

ObjectiveThis paper aims to analyze the clinical characteristics and medication rationality of liver injury related to Epimedii Folium preparation （EP） and explore the possible risk factors of liver injury， so as to provide a reference for the safe clinical application of Epimedii Folium （EF）. MethodA retrospective analysis was conducted on liver injury cases related to EP from 2012 to 2016. ResultThe number of reported liver injury cases and the proportion of severe cases related to the use of EP show an increasing trend， indicating the objective existence of liver injury caused by EP. There are more cases of liver injury related to EP in women than in men， with an onset age range of 15-91 years old and a median onset age of 60 years old （median onset ages for men and women are 59 and 60 years old， respectively）. The time span from taking EP alone to the occurrence of liver injury is 1-386 days， with a median of 38 days. The time span from taking both EP and Western medicine to the occurrence of liver injury is 1-794 days， with a median of 34 days. EF-related liver injury preparations are mostly composed of traditional Chinese medicines that promote immunity and tonify the liver and kidney， indicating that immune stress in the body may be the mechanism of liver injury caused by the use of EP alone or in combination. There is no increasing trend of toxicity with time or dose in the liver injury caused by EP. By further exploring its risk factors， it is found that patients have unreasonable medication methods such as excessive dosage， repeated use， and multi-drug combination， which may also be one of the important risk factors for EF-related liver injury. ConclusionEP has a certain risk of liver injury and should be emphasized in clinical diagnosis and treatment. Immune stress may be the mechanism of liver injury caused by EP， and in clinical use， it is necessary to be vigilant about the risk of liver injury caused by unreasonable use and combined use with Western medicine.

Childhood lichenoid granulomatous stomatitis: a case report and literature review / 口腔疾病防治

Objective@#To investigate the classification, clinical manifestations, diagnosis, differential diagnosis and treatment of oral lichenoid lesions and provide a reference for clinical practice.@*Methods@#Hospital ethical approval and patient informed consent were obtained. We report a case of oral lichenoid lesion in children and review the diagnosis and treatment of oral lichenoid damage in the literature.@*Results@#The patient experienced repeated rupture of the dorsal surface of the tongue with pain for more than 3 years. There was a large area of tongue back surface erosion with an irregular shape, surrounded by pearly-white lines. The left erosive area was accompanied by tissue hyperplasia, which was approximately 1.5 cm × 2.0 cm, with tough texture and broad masses. The pathological diagnosis of the patient was oral lichenoid lesion. After biopsy of the dorsal surface of the tongue, the pathological diagnosis of the patient was granulomatous inflammation. The final diagnosis of lichenoid granulomatous stomatitis was made on the basis of the patient's intraoral damage features, systemic history, medication history and histopathological findings. A review of the literature suggests that oral lichenoid lesions have an unknown etiology and need to be clinically differentiated from oral lichen planus, oral lichenoid drug reactions, oral lichenoid contact damage and chronic ulcerative stomatitis. The clinical treatment of oral lichen planus is based on the topical and/or systemic use of glucocorticoids.@*Conclusion@#There are still no uniform criteria for the classification and diagnosis of oral lichenoid lesions. They rely mainly on history taking, clinical manifestations and histopathological findings, and the treatment is mainly based on the topical and/or systemic use of glucocorticoids.