Hemorragia digestiva por intususcepción de un lipoma ulcerado en yeyuno / Gastrointestinal bleeding due to ulcerated intussuscepted jejunal lipoma

RESUMEN Los lipomas yeyunales son tumores gastrointestinales benignos e infrecuentes, de origen mesenquimático, compuestos por adipocitos que suelen estar confinados a la submucosa. Generalmente son asintomáticos y se descubren de manera incidental al realizar estudios por imágenes o endoscópicos. Sin embargo, aquellos mayores de 2 cm pueden presentar síntomas como resultado de complicaciones, como intususcepción intestinal, obstrucción o rara vez, hemorragias. Presentamos un caso infrecuente de intususcepción de un lipoma yeyunal ulcerado en un adulto, diagnosticado en el contexto de un cuadro de hemorragia digestiva.

ABSTRACT Jejunal lipomas are rare benign mesenchymal tumors made up of adipocytes confined to the submucosa layer. They are usually asymptomatic and are incidentally found during imaging or endoscopic tests. Those measuring > 2 cm may become symptomatic as a result of complications as intestinal intussusception, obstruction and bleeding. We herein report a rare case of intussusception of an ulcerated jejunal lipoma in an adult patient, that was diagnosticated in the setting of an intestinal hemorrhage.

Small Molecules Accelerate Skin Wound Healing: Shikonin Efficacy and Mechanism of Action in Mice / Las Moléculas Pequeñas Aceleran la Curación de Heridas en la Piel: Eficacia de Shikonin y Mecanismo de Acción en Ratones

SUMMARY: The objective of this study was to investigate the therapeutic wound healing potential and molecular mechanisms of shikonin as small molecules in vitro. A mouse burn model was used to explore the potential therapeutic effect of shikonin; we traced proliferating cells in vivo to locate the active area of skin cell proliferation. Through the results of conventional pathological staining, we found that shikonin has a good effect on the treatment of burned skin and promoted the normal distribution of skin keratin at the damaged site. At the same time, shikonin also promoted the proliferation of skin cells at the damaged site; importantly, we found a significant increase in the number of fibroblasts at the damaged site treated with shikonin. Most importantly, shikonin promotes fibroblasts to repair skin wounds by regulating the PI3K/AKT signaling pathway. This study shows that shikonin can effectively promote the proliferation of skin cell, and local injection of fibroblasts in burned skin can play a certain therapeutic role.

El objetivo de este trabajo fue investigar el potencial terapéutico de cicatrización de heridas y los mecanismos moleculares de la shikonina como moléculas pequeñas in vitro. Se utilizó un modelo de quemaduras en ratones para explorar el posible efecto terapéutico de la shikonina; Rastreamos las células en proliferación in vivo para localizar el área activa de proliferación de células de la piel. A través de los resultados de la tinción para patología convencional, encontramos que la shikonina tiene un buen efecto en el tratamiento de la piel quemada y promueve la distribución normal de la queratina de la piel en el sitio dañado. Al mismo tiempo, la shikonina también promovió la proliferación de células de la piel en el sitio dañado. Es importante destacar que encontramos un aumento significativo en la cantidad de fibroblastos en el sitio dañado tratado con shikonina. Lo más importante es que la shikonina promueve la función reparadora de fibroblastos en las heridas de la piel regulando la vía de señalización PI3K/ AKT. Este estudio muestra que la shikonina puede promover eficazmente la proliferación de células de la piel y que la inyección local de fibroblastos en la piel quemada puede desempeñar un cierto papel terapéutico.

Neuron parvum fluorescens, un Término con Influencia Anglo-Greco-Latina. Propuesta a Terminologia Neuroanatomica y Terminologia Histologica / Neuron Parvum Fluorescens, a Term with Anglo-Greco-Latin Influence. A Proposal to Terminologia Neuroanatomica and Terminologia Histologica

Las terminologías son utilizadas como instrumento lingüístico que permite la transmisión de conocimiento de manera precisa y sin ambigüedades en el ámbito de las ciencias. Los lineamientos de la Federative International Programme for Anatomical Terminology (FIPAT) refieren que la denominación de nombres estructurales debe ser descriptivos e informativos. Este estudio analiza las raíces lingüísticas que componen el término Neuron parvum valde fluorescens vigente en Terminologia Histologica y el término Neuron parvum fluorescens vigente en Terminologia Neuroanatomica. Las células pequeñas intensamente fluorescentes son neuronas que se encuentran en el sistema nervioso autónomo, distribuidas en los ganglios simpáticos. Estas células presentan sinapsis aferentes con terminales nerviosas simpáticas preganglionares y sinapsis eferentes con las dendritas de las neuronas posganglionares. Su función es regular la transmisión ganglionar, actuando como interneuronas con señalización paracrina y endocrina. Además, se caracterizan por ser células fluorescentes, que expresan catecolaminas; serotonina, noradrenalina y dopamina. Se realizó una búsqueda en Terminologia Histologica y Terminologia Neuroanatomica, con una traducción de los términos al español. Además, la búsqueda se complementó en un diccionario etimológico en inglés para los términos correspondientes. Esta investigación encontró diferencia entre la traducción del latín al español del término fluorescens, quien posee un origen etimológico muy diferente a su significado en español. El término Neuron parvum valde fluorescens en Terminologia Histologica y el término Neuron parvum fluorescens en Terminologia Neuroanatomica, identifican a la misma estructura. Se sugiere reemplazar ambos términos por Cateconeuron ganglionare, entregando así una correcta descripción de este tipo de neurona, considerando su ubicación y función. Además, de esta manera ser un término concordante en latín para su incorporación en Terminologia Neuroanatomica y Terminologia Histologica.

SUMMARY: Terminologies are used as a linguistic tool to convey knowledge in a precise and unambiguous manner in science. The guidelines of the Federative International Programme for Anatomical Terminology (FIPAT) state that the names given to structures should be both descriptive and informative. This study analyses the linguistic roots of the term Neuron parvum valde fluorescens in Terminologia Histologica and the term Neuron parvum fluorescens in Terminologia Neuroanatomica. Small intensely fluorescent cells are neurons found in the autonomic nervous system, distributed in the sympathetic ganglia, they have afferent synapses with preganglionic sympathetic nerve terminals and efferent synapses with the dendrites of postganglionic neurons, whose function is to regulate ganglionic transmission, acting as interneurons with paracrine and endocrine signalling. They are also characterized as fluorescent cells, producing the catecholamines: serotonin, noradrenaline and dopamine. A search was carried out in Terminologia Histologica and Terminologia Neuroanatomica, with a translation of the terms into Spanish. This was complemented by a search in an English etymological dictionary for the corresponding terms. This research found a difference between the Latin to English translation of the term fluorescens, which has a very different etymological origin to its English meaning. The term Neuron parvum valde fluorescens in Terminologia Histologica and the term Neuron parvum fluorescens in Terminologia Neuroanatomica identify the same structure. The proposal is to replace both terms with Cateconeuron ganglionare, thus affording an accurate description of this type of neuron, considering its location and function. Moreover, it would also be a concordant term in Latin for its incorporation into the Terminologia Neuroanatomica and Terminologia Histologica.

Pediatric kidney transplantation: outcomes with under and over 6-year-old donors

Abstract Objective Kidney shortage for pediatric kidney transplantation (PKT) entails the need to use low-weight and age donors, despite the apprehension. The aim of this study was to analyze the pediatric deceased donor kidney transplantations (pDDKT) outcomes in the first year after the procedure, stratified by donor age. Method Retrospective cohort of pDDKTs carried out between January 2013, and January 2018, at a PKT reference hospital in Southern Brazil. Donors were divided into group 1 (≤ 6 years), and group 2 (> 6 years); the analysis of the outcomes was carried out in the same period. Results There were 143 pDDKTs; 51 (35.66%) in group 1; and 92 (64.34%) in group 2. In both groups there were 17 graft losses (11.8%), with vascular thrombosis as the main cause (group 1: 5; group 2: 4). Among the complications, renal artery stenosis (RAS) with indication for angioplasty and stenting was more frequent in group 1 (7.8%; group 2: 2.2%). The 1-year Renal Transplant Recipients' and graft survival did not show significant differences between the groups, (p= = 0.95). However, the Glomerular Filtration Rate analysis was higher in group 2, reaching, in the 12th month, 79.3 mL/min/1,73m2, compared to 69.7 mL/min/1,73m2 in group 1(p= = 0.033). Conclusions Small donors can be considered for pDDKTs, as long as there is an expert team to perform the transplantation.

Effect of treatment with growth hormone on body composition and metabolic profile of short children born small for gestational age / Efeito do tratamento com hormônio de crescimento na composição corporal e no perfil metabólico de crianças nascidas pequenas para a idade gestacional com baixa estatura

ABSTRACT Objective: To assess the effect of recombinant growth hormone (rGH) on body composition and metabolic profile of prepubertal short children born small for gestational age (SGA) before and after 18 months of treatment. Methods: It is a clinical, non-randomized, and paired study. Children born SGA, with birth weight and/or length <-2 standard deviations (SD) for gestational age and sex, prepubertal, born at full term, of both genders, with the indication for treatment with rGH were included. The intervention was performed with biosynthetic rGH at doses ranging from 0.03 to 0.05 mg/kg/day, administered subcutaneously, once a day at bedtime. Total lean mass (LM) and total fat mass (FM) were carried out using dual-energy X-ray absorptiometry (DXA), and the metabolic profile was assessed for insulin, glycemia, IGF-1 levels and lipid profile. Results: Twelve patients (nine girls, 8.17±2.39 y) were evaluated; three patients dropped out of the study. There was an increase of LM adjusted for length (LMI) (p=0.008), LMI standard deviation score (SDS) adjusted for age and sex (p=0.007), and total LM (p<0.001). The percentage of body fat (BF%) and abdominal fat (AF) remained unaltered in relation to the beginning of treatment. Among the metabolic variables, blood glucose remained within normal levels, and there was a reduction in the number of participants with altered cholesterol (p=0.023). Conclusions: The effect of rGH treatment was higher on LM than in FM, with increased LM adjusted for length and standardized for age and sex. Glycemia remained within the normal limits, and there was a decreased number of children with total cholesterol above the recommended levels.

RESUMO Objetivo: Avaliar o efeito do hormônio de crescimento recombinante (rHC) na composição corporal e no perfil metabólico de crianças pré-púberes com baixa estatura, nascidas pequenas para a idade gestacional (PIG) antes e depois de 18 meses de tratamento. Métodos: Estudo clínico, não randomizado e pareado. Foram incluídas crianças nascidas PIG, com peso e/ou altura ao nascer <-2 desvios padrão (DP) para idade gestacional e sexo, pré-púberes, nascidas a termo, de ambos os sexos, com indicação de tratamento com rGH. A intervenção foi realizada com rGH biossintético com doses variando de 0,03 a 0,05 mg/kg/dia, administrado por via subcutânea, uma vez ao dia ao deitar-se. A massa magra total (LM) e a massa gorda total (MG) foram determinadas por meio de absorciometria de raios X de dupla energia (DXA), e o perfil metabólico foi avaliado com dosagens de insulina, glicemia, IGF-1 e perfil lipídico. Resultados: Doze pacientes (nove meninas, 8,17±2,39 anos) foram avaliados; três pacientes abandonaram o estudo. Houve aumento da LM ajustada para estatura (LMI) (p=0,008), LMI standard deviation scores (SDS) ajustada para idade e sexo (p=0,007) e LM total (p<0,001). O percentual de gordura corporal (GC%) e gordura abdominal (AF) permaneceu inalterado em relação ao início do tratamento. Entre as variáveis metabólicas, a glicemia manteve-se na normalidade, e houve redução do número de participantes com colesterol alterado (p=0,023). Conclusões: O efeito do tratamento com HCr foi maior na MM do que na MG, com o aumento da MM ajustada para altura e padronizada para idade e sexo. A glicemia permaneceu normal e houve redução do número de crianças com colesterol total acima do recomendado.

Prokaryotic expression and functional analysis of molecular chaperone Acr2 protein of Mycobacterium tuberculosis / 中国生物制品学杂志

@#Objective To express the molecular chaperone Acr2 protein of Mycobacterium tuberculosis(Mtb)in E.coli and analyze the function. Methods The recombinant plasmid pET-28a-Acr2 was transformed into competent E. coli BL21(DE3),and induced by IPTG. The expressed His-Acr2 protein was purified by Ni-NTA chromatography and SuperdexTM200 10/300 GL gel filtration chromatography to obtain Acr2 protein. The Acr2 protein was refolded by spontaneous refolding and reassembly after thermal denaturation(100 ℃ for 15 min)and chemical denaturation(8 mol/L urea,37 ℃ for 4 h).The secondary structure of Acr2 protein before and after denaturation-renaturation was detected by circular dichroism spectroscopy and non-denaturing SDS-PAGE,and the molecular chaperone function of Acr2 protein in vitro was detected by substrate binding assay. Results The purified Acr2 protein had the relative molecular mass of about 232 000,the purity of over 90%,and the concentration of about 2 mg/mL,which recovered its natural secondary structure after denaturationrenaturation,and formed stable complexes with the denatured malate dehydrogenase(MDH)at 48 ℃. Conclusion The Acr2protein can restore its natural molecular conformation with molecular chaperone activity in vitro after denaturation-renaturation treatment,providing a new strategy for the preparation of Mtb protein antigen with natural activity.

Clinical characteristics and influencing factors of chronic obstructive pulmonary disease in patients with non-small cell lung cancer in Hubei province / 公共卫生与预防医学

Objective To analyze the clinical characteristics and influencing factors of non-small cell lung cancer (NSCLC) patients with chronic obstructive pulmonary disease (COPD) in Hubei province, and to provide a theoretical basis for the diagnosis and treatment of NSCLC patients with COPD. Methods A total of 246 NSCLC patients admitted to our hospital from 2018 to 2020 were selected and divided into control group (without COPD, n=125) and observation group (with COPD, n=121) according to COPD. The clinical characteristics of chest pain, hemoptysis, emasculation, atelectasis and pleural effusion were compared between the two groups. The values of FEV1/FVC, RV/TLC and DLCO in the two groups were measured by pulmonary function detector. The age, gender, smoking, smoking history, proportion of lung squamous cell carcinoma, TNM stage and other clinical data of all subjects were analyzed by self-made survey scale of our hospital. Univariate analysis and logistic regression were used to analyze the risk factors of COPD in NSCLC patients. Results Among 246 NSCLC patients, 121 patients (49.19%) were complicated with COPD, including 76 males and 45 females, and there was a statistical difference between the two groups (χ2=4.891, P>0.05). The average age of the observation group (61.02±4.82) was significantly higher than that of the control group (59.76±4.73) (t=2.069, P0.05). Male (OR=2.982), smoking history (OR=2.623) and lung squamous cell carcinoma (OR=3.147) were risk factors for COPD in NSCLC patients (P<0.05). Conclusions NSCLC patients with COPD are more common in male smokers in Hubei Province, often accompanied by pleural effusion , severe hemoptysis and other symptoms , and their lung function is decreased. Early detection and standardized treatment of COPD in the treatment of NSCLC can improve the prognosis of patients.

Role of post-translational modification of basic leucine zipper transcription factors in response to abiotic stresses in plants / 生物工程学报

Abiotic stresses substantially affect the growth and development of plants. Plants have evolved multiple strategies to cope with the environmental stresses, among which transcription factors play an important role in regulating the tolerance to abiotic stresses. Basic leucine zipper transcription factors (bZIP) are one of the largest gene families. The stability and activity of bZIP transcription factors could be regulated by different post-translational modifications (PTMs) in response to various intracellular or extracellular stresses. This paper introduces the structural feature and classification of bZIP transcription factors, followed by summarizing the PTMs of bZIP transcription factors, such as phosphorylation, ubiquitination and small ubiquitin-like modifier (SUMO) modification, in response to abiotic stresses. In addition, future perspectives were prospected, which may facilitate cultivating excellent stress-resistant crop varieties by regulating the PTMs of bZIP transcription factors.

The Uptake and Distribution Evidence of Nano- and Microplastics in vivo after a Single High Dose of Oral Exposure / 生物医学与环境科学（英文）

OBJECTIVE@#Tissue uptake and distribution of nano-/microplastics was studied at a single high dose by gavage in vivo.@*METHODS@#Fluorescent microspheres (100 nm, 3 μm, and 10 μm) were given once at a dose of 200 mg/(kg∙body weight). The fluorescence intensity (FI) in observed organs was measured using the IVIS Spectrum at 0.5, 1, 2, and 4 h after administration. Histopathology was performed to corroborate these findings.@*RESULTS@#In the 100 nm group, the FI of the stomach and small intestine were highest at 0.5 h, and the FI of the large intestine, excrement, lung, kidney, liver, and skeletal muscles were highest at 4 h compared with the control group ( P < 0.05). In the 3 μm group, the FI only increased in the lung at 2 h ( P < 0.05). In the 10 μm group, the FI increased in the large intestine and excrement at 2 h, and in the kidney at 4 h ( P < 0.05). The presence of nano-/microplastics in tissues was further verified by histopathology. The peak time of nanoplastic absorption in blood was confirmed.@*CONCLUSION@#Nanoplastics translocated rapidly to observed organs/tissues through blood circulation; however, only small amounts of MPs could penetrate the organs.

Longitudinal study on catch-up growth in preterm infants with small for gestational age at corrected ages 0-24 months / 中国当代儿科杂志

OBJECTIVES@#To understand the growth and development status and differences between small for gestational age (SGA) and appropriate for gestational age (AGA) preterm infants during corrected ages 0-24 months, and to provide a basis for early health interventions for preterm infants.@*METHODS@#A retrospective study was conducted, selecting 824 preterm infants who received regular health care at the Guangzhou Women and Children's Medical Center from July 2019 to July 2022, including 144 SGA and 680 AGA infants. The growth data of SGA and AGA groups at birth and corrected ages 0-24 months were analyzed and compared.@*RESULTS@#The SGA group had significantly lower weight and length than the AGA group at corrected ages 0-18 months (P<0.05), while there were no significant differences between the two groups at corrected age 24 months (P>0.05). At corrected age 24 months, 85% (34/40) of SGA and 79% (74/94) of AGA preterm infants achieved catch-up growth. Stratified analysis by gestational age showed that there were significant differences in weight and length at corrected ages 0-9 months between the SGA subgroup with gestational age <34 weeks and the AGA subgroups with gestational age <34 weeks and 34 weeks (P<0.05). In addition, the weight and length of the SGA subgroup with gestational age 34 weeks showed significant differences compared to the AGA subgroups with gestational age <34 weeks and 34 weeks at corrected ages 0-18 months and corrected ages 0-12 months, respectively (P<0.05). Catch-up growth for SGA infants with gestational age <34 weeks and 34 weeks mainly occurred at corrected ages 0-12 months and corrected ages 0-18 months, respectively.@*CONCLUSIONS@#SGA infants exhibit delayed early-life physical growth compared to AGA infants, but can achieve a higher proportion of catch-up growth by corrected age 24 months than AGA infants. Catch-up growth can be achieved earlier in SGA infants with a gestational age of <34 weeks compared to those with 34 weeks.

Progress on the relationship of aldehyde dehydrogenase 2 with human diseases and its small-molecule activators / 药学实践杂志

Aldehyde dehydrogenase 2 (ALDH2) is one of important factors against from the damage under oxidative stress in human body. A high proportion of East Asians carry ALDH2 inactive mutation gene. There are many diseases closely related to ALDH2, such as cardiovascular diseases, neurodegenerative diseases and liver diseases. Recent studies also have found that ALDH2 is associated with ferroptosis. Therefore, ALDH2 has becoming a potential target for the treatment of the above related diseases. Several types of small molecule activators with potential value of clinical application have been reported. The research progress on the structure and function of ALDH2 , the relationship with human diseases and its activators were summarized in this paper.

Clinical effect of cross positioning method for correcting low and moderate astigmatism during small incision lenticule extraction / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To evaluate the clinical outcomes of using the cross-positioning method for correcting low and moderate astigmatism during small incision lenticule extraction(SMILE)surgery with Alpins vector analysis.METHODS: A total of 50 patients(81 eyes)with low and moderate astigmatism with the rule ≤1.50 D who underwent SMILE surgery at the laser myopia treatment center of Xi'an No.1 Hospital from May 2022 to November 2022 were included in the prospective randomized controlled study, and they were divided into two groups according to the random table, with 25 case(41 eyes)in cross-positioning group and 25 cases(40 eyes)in control group. In the cross-positioning group, the patients' head position was adjusted based on the cross intersection lines before the standard SMILE procedure, aligning the lateral canthi with the horizontal line and the midpoint of the eyebrows and the nose bridge with the vertical line. Postoperative visual acuity and refractive results at 3 mo were observed in both groups, and astigmatic changes were analyzed and evaluated using the Alpins vector analysis method.RESULTS: During the follow-up period, 6 cases(11 eyes)in the cross-positioning group were lost to follow-up, while in the control group, 8 cases(14 eyes)were lost to follow-up, with 19 cases(30 eyes)and 17 cases(26 eyes)finally included in the cross-positioning group and the control group, respectively. At 3 mo postoperatively, the uncorrected visual acuity(UCVA)of both groups' operated eyes was ≥1.0, and no serious complications occurred, with no significant differences in UCVA, best corrected visual acuity(BCVA), spherical power, and spherical equivalent between the cross-positioning group and the control group(all P&#x0026;#x003E;0.05). The cylindrical power in the cross-positioning group was 0.00(0.00, 0.00)D, which was lower than -0.13(-0.50, 0.00)D in the control group(P=0.01). The vector analysis results showed that the difference vector(DV)in the cross-positioning group was lower than that in the control group [0.00(0.00, 0.00)vs 0.13(0.00, 0.50), P=0.01], and the index of success(IOS)was better than that of the control group [0.00(0.00, 0.00)vs 0.18(0.00, 0.77), P&#x0026;#x003C;0.01]. At 3 mo postoperatively, 26(87%)and 15(58%)eyes in the cross-positioning group and control groups achieved an angle of error(AE)within ±5°, respectively.CONCLUSION: The cross positioning method was used to calibrate the patients' head position during SMILE surgery, which reduced the axial position error and improved the accuracy of SMILE in correcting low and moderate astigmatism.

Buzhong Yiqitang Regulates Apoptosis via Nrf2/ROS Pathway to Alleviate Cisplatin Resistance in A549/DDP Cells / 中国实验方剂学杂志

ObjectiveTo explore the mechanism of Buzhong Yiqitang-containing serum in alleviating the cisplatin resistance in human non-small cell lung cancer （A549/DDP） cells via regulating the nuclear factor E2-related factor 2 （Nrf2）/reactive oxygen species （ROS） signaling pathway. MethodThe serum containing Buzhong Yiqitang was prepared and A549/DDP cells were cultured and randomly grouped： blank （10% blank serum）， cisplatin （10% blank serum+20 mg·L-1 cisplatin）， Buzhong Yiqitang （10% Buzhong Yiqitang-containing serum+20 mg·L-1 cisplatin）， ML385 （10% blank serum+5 μmol·L-1 ML385+20 mg·L-1 cisplatin）， Buzhong Yiqitang+ML385 （10% Buzhong Yiqitang-containing serum+5 μmol·L-1 ML385+20 mg·L-1 cisplatin）， tertiary butylhydroquinone （TBHQ） （10% blank serum+5 μmol·L-1 TBHQ+20 mg·L-1 cisplatin）， and Buzhong Yiqitang+TBHQ （10% Buzhong Yiqitang-containing serum+5 μmol·L-1 TBHQ+20 mg·L-1 cisplatin）. The median inhibitory concentration （IC50） of cisplatin in each group was determined by the cell counting kit-8 （CCK-8） method and the resistance index （RI） was calculated. The apoptosis rate was detected by flow cytometry. The ROS content of each group was determined with the DCFH-DA fluorescence probe. Western blot was employed to determine the protein levels of Nrf2， cleaved cysteinyl aspartate-specific protease-3 （cleaved Caspase-3）， cytochrome C （Cyt C）， and B-cell lymphoma-2 （Bcl-2）. ResultCompared with those in the cisplatin group， the IC50 and RI of A549/DDP cells to cisplatin in Buzhong Yiqitang， ML385， and Buzhong Yiqitang+ML385 groups decreased （P˂0.05）. Compared with the blank group， the cisplatin， Buzhong Yiqitang， ML385， and Buzhong Yiqitang+ML385 groups showed increased apoptosis rate of A549/DDP cells （P˂0.05）. Compared with the blank group， cisplatin promoted the expression of Nrf2 （P˂0.05）. Compared with the cisplatin group， Buzhong Yiqitang， ML385， and Buzhong Yiqitang+ML385 inhibited the expression of Nrf2 （P<0.05）， elevated the ROS level （P˂0.05）， up-regulated the protein levels of cleaved Caspase-3 and Cyt C， and down-regulated the protein level of Bcl-2 （P<0.05）， which were the most significant in the Buzhong Yiqitang+ML385 group. Compared with the cisplatin group， the TBHQ group showed increased IC50 and RI of cisplatin （P<0.05）， decreased apoptosis rate of A549/DDP cells （P<0.05）， up-regulated protein levels of Nrf2 and Bcl-2 （P<0.05）， lowered level of ROS （P˂0.05）， and down-regulated protein levels of cleaved Caspase-3 and Cyt C （P<0.05）. Compared with the TBHQ group， Buzhong Yiqitang+TBHQ decreased the IC50 and RI of cisplatin in A549/DDP cells （P<0.05）， increased the apoptosis rate （P<0.05）， down-regulated the protein levels of Nrf2 and Bcl-2 （P<0.05）， increased ROS （P˂0.05）， and up-regulated the protein levels of cleaved Caspase-3 and Cyt C （P<0.05）. ConclusionBuzhong Yiqitang induced apoptosis by inhibiting Nrf2/ROS pathway to alleviate cisplatin resistance in A549/DDP cells.

Effect and mechanism of gracillin-induced autophagy in lung cancer A549 cells / 中国药房

OBJECTIVE To investigate the effect and mechanism of gracillin from Reineckia carnea on autophagy in non- small cell lung cancer A549 cells. METHODS Using A549 cells as subjects， the effects of different concentrations of gracillin （0.25， 0.5， 1， 2， 4 μmol/L） on the proliferation of cells were detected by CCK-8 after being treated for different time （12， 24， 48 h）. Compared with the control group without medication， the effect of gracillin （2 μmol/L） on the formation of autophagosomes in cells was observed by transmission electron microscope after 24 h of exposure. The aggregation of GFP-LC3 on autophagosome membrane was detected by GFP-LC3 plasmid transfection after being treated with gracillin （0.25， 0.5， 1， 2 μmol/L） for 24 h. Quantitative real-time PCR and Western blot assay were used to detect the mRNA and protein expressions of family with sequence similarity 102 member A（FAM102A）， the expressions of autophagy-related proteins [p62， Beclin-1， microtubule-associated protein 1 light chain 3B （LC3B）]， and the expressions of phosphoinositide 3-kinase （PI3K）/protein kinase B （Akt） signaling pathway-related proteins in A549 cells after being treated with gracillin （0.25， 0.5， 1 and 2 μmol/L） for 24 h. RESULTS Gracillin significantly inhibited the proliferation of A549 cells in a concentration- and time-dependent manner. The IC50 was 2.55 μmol/L at 24 h. After 24 h of gracillin treatment， autophagosomes with bilayer membrane structure were found in the cell cytoplasm， and GFP-LC3 green fluorescent spots on autophagosome membrane were obvious， representing an increasing trend as drug concentration. Compared with the control group， mRNA and protein expressions of FAM102A （0.5， 1， 2 μmol/L groups）， protein expression of Beclin-1 （1， 2 μmol/L groups） and LC3B-Ⅱ/LC3B-Ⅰ ratio （2 μmol/L group） were significantly increased in different concentrations of gracillin groups， while the protein expression of p62 （1， 2 μmol/L groups）， and the protein phosphorylations of Akt （1， 2 μmol/L groups） and PI3K （2 μmol/L group） were all decreased significantly （P＜0.05 or P＜0.01）. CONCLUSIONS Gracillin can promote excessive autophagy in A549 cells by up-regulating mRNA and protein expressions of FAM102A and inhibiting PI3K/Akt signaling pathway， thus inhibiting cell proliferation.

Research progress on endogenous small-molecule phenolics and the proposal of "phenolomics" / 药学学报

Small-molecule phenolic substances widely exist in animals and plants, and have some shared biological activities. The metabolism of phenylalanine and tyrosine in the human body, and especially the metabolism of catecholamine neurotransmitters, produces endogenous small-molecule phenols. Endogenous small-molecule phenolic substances are functionally related to the important physiological processes and the occurrence of mental diseases in humans and some animals, which are systematically sorts and summarized in this review. Integrating the previous experimental research and literature analysis on natural small-molecule phenols by our research group, the understanding of the hypothesis that "small-molecule phenol are pharmacological signal carriers" was deepened. Based on above, the concept of "phenolomics" was further proposed, analyzed the research direction and research content which can bring into the knowledge framework of phenolomics. The induction of phenolomics will provide wider perspectives on explaining the pharmacological mechanism of drugs, discovering new drug targets, and finding biomarkers of mental diseases.

First-in-class small molecule drugs in 2023 / 药学学报

In 2023, drug discovery develops steadily, with improvement of small molecule drugs discovery keeps pace with biological drugs in this year. The Center for Drug Evaluation and Research of U.S. Food and Drug Administration has totally approved 55 kinds of new drugs which have significantly promotion compared to 37 new drugs approval in 2022, including 38 kinds of new molecular entities, 17 kinds of biological drugs, 5 kinds of gene therapeutics and 2 cell therapeutics. The proportion of first-in-class drugs increased steadily, with 13 small molecule first-in-class drugs and 7 biological first-in-class drugs approved this year, mostly in the fields of cancer and rare diseases. Among them, a plurality of first-initiated small molecule drugs exhibits breakthrough significance, such as the first neurokinin 3 (NK3) receptor antagonist fezolinetant, the first retinoic acid receptor (RIG-I) agonist palovarotene, the first protein kinase B (AKT) inhibitor capivasertib, the first complement factor B inhibitor iptacopan, etc. The pioneering drug has huge academic and commercial value, and has become the target of the academic and industrial circles. However, first-in-class drugs not only need new targets, new mechanisms and new molecules, but also need to comprehensively verify the causality between new targets and diseases, study the correlation between new mechanisms and drug efficacy, and explore the balance between new molecules and drug-manufacturing properties. This article analyzed the research background, development process and therapeutic application of three first-initiated small molecule drugs in this year, expecting to provide more research ideas and methods for more first-in-class drugs.

Anti-SARS-CoV-2 activity of small molecule inhibitors of cathepsin L / 药学学报

The coronavirus disease 2019 (COVID-19) is an acute infectious disease caused by the new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, which has led to serious worldwide economic burden. Due to the continuous emergence of variants, vaccines and monoclonal antibodies are only partial effective against infections caused by distinct strains of SARS-CoV-2. Therefore, it is still of great importance to call for the development of broad-spectrum and effective small molecule drugs to combat both current and future outbreaks triggered by SARS-CoV-2. Cathepsin L (CatL) cleaves the spike glycoprotein (S) of SARS-CoV-2, playing an indispensable role in enhancing virus entry into host cells. Therefore CatL is one of the ideal targets for the development of pan-coronavirus inhibitor-based drugs. In this study, a CatL enzyme inhibitor screening model was established based on fluorescein labeled substrate. Two CatL inhibitors IMB 6290 and IMB 8014 with low cytotoxicity were obtained through high-throughput screening, the half inhibition concentrations (IC50) of which were 11.53 ± 0.68 and 1.56 ± 1.10 μmol·L-1, respectively. SDS-PAGE and cell-cell fusion experiments confirmed that the compounds inhibited the hydrolysis of S protein by CatL in a concentration-dependent manner. Surface plasmon resonance (SPR) detection showed that both compounds exhibited moderate binding affinity with CatL. Molecular docking revealed the binding mode between the compound and the CatL active pocket. The pseudovirus experiment further confirmed the inhibitory effects of IMB 8014 on the S protein mediated entry process. In vitro pharmacokinetic evaluation indicated that the compounds had relatively good drug-likeness properties. Our research suggested that these two compounds have the potential to be further developed as antiviral drugs for COVID-19 treatment.

Research progress of anti-gout small molecules targeting the NLRP3 inflammasome / 药学学报

Currently, clinically used drugs for the treatment of gout inflammation, such as colchicine, nonsteroidal anti-inflammatory drugs, and glucocorticoids, can only relieve the pain of joint inflammation and have severe hepatorenal toxicity and multiple organ adverse reactions. The NOD-like receptor thermal protein domain associated protein 3 (NLRP3) inflammasome is a key complex that induces the onset of gout inflammation and has become a crucial target in the development of anti-gout drugs. This article reviews the research progress of anti-gout small molecules targeting the NLRP3 inflammasome and their bioactivity evaluation methods in the past five years, in order to provide information for the development of specific drugs for the treatment of gout inflammation.

Treatment Strategy and Research Progress of Immune Microenvironment for Liver Metastasis of Non-small Cell Lung Cancer / 肿瘤防治研究

Liver is the common site for metastasis and spread of non-small cell lung cancer (NSCLC). Lung cancer patients with liver metastasis have poor prognosis, which may be related to liver-specific microenvironment composition. The metastasis of lung cancer to the liver is regulated by various pathophysiological factors, including the liver immune microenvironment, related cells, proteins, signaling molecules, and gene changes. These factors will affect the consistent disease process and subsequent treatment strategies. Immune checkpoint inhibitors (ICIs) have made breakthroughs in treatment of patients with advanced NSCLC. However, NSCLC patients with liver metastasis, a unique population of advanced lung cancer, are characterized by poor immunotherapeutic effect. This paper reviews the related mechanisms of the immune microenvironment in affecting the occurrence and development of liver metastases and summarizes the achievements and prospects of anti-tumor immunotherapy in liver metastases of NSCLC.

Therapeutic Effect of Savolitinib in Patients with Stage Ⅲ/Ⅳ Non-small Cell Lung Cancer / 肿瘤防治研究

Objective To analyze therapeutic effect of savolitinib in patients with stage Ⅲ/Ⅳ non-small cell lung cancer (NSCLC). Methods A total of 95 patients with MET 14 exon (METex14) jumping mutation in stage Ⅲ/Ⅳ NSCLC were divided into a control group (47 cases) and an observation group (48 cases) through a random-number table method. The patients in the control group were treated with crizotinib, whereas those in the observation group were treated with savolitinib. The clinical efficacy and incidence of toxic side effects in both groups were evaluated through a chi-square test, and survival was evaluated through Kaplan-Meier survival analysis. Results Compared with control group (31.91% and 70.21%), the objective response rate and disease control rate of the observation group were 52.08% and 87.50%, respectively (P<0.05). According to Kaplan-Meier survival analysis, the overall survival and progression free survival rates in the observation group were higher than those in the control group (Log rank χ2=8.003, 4.528; P=0.005, 0.033). No statistically significant difference in the degree of toxic side effects was found between the groups (P>0.05). Conclusion Savolitinib can improve the efficacy of treatment for stage Ⅲ/Ⅳ METex14 skip mutation NSCLC patients, prolong survival, enhance the tolerance of patients to savolitinib, and facilitate the management of adverse reactions.