Strategy and Status of Neoadjuvant Therapy for HER2-positive Breast Cancer / 肿瘤防治研究

Neoadjuvant therapy is a preoperative systemic treatment for patients with breast cancer. This therapy has greatly improved the clinical outcomes of human epidermal growth factor receptor 2 (HER2)-positive breast cancer, which is associated with poor prognosis. Currently, dual anti-HER2 antibodies, including trastuzumab and pertuzumab, combined with non-anthracycline chemotherapy is one of the standard regimens to achieve high pathologic complete response rate and satisfactory efficacy. The combination of trastuzumab with tyrosine kinase inhibitors, antibody-drug conjugate drugs, or immunotherapy combined with target therapy, under the indications of reasonable biomarkers, is effective for HER2-positive breast cancer. In this article, we briefly reviewed neoadjuvant therapy in the dual-targeting therapy era and discussed its future perspectives.

A virtual simulation system-based teaching method for the experimental course of oral local nerve block anesthesia / 中华医学教育探索杂志

Objective:To investigate the effect of the virtual simulation system-based teaching method for the experimental course of oral local nerve block anesthesia in improving the effect of traditional teaching methods.Methods:One hundred and eighteen undergraduate dental students were randomly divided into two groups, the experimental group was taught using a virtual simulation-based system, and the control group was taught using traditional teaching. The results of the teaching were comprehensively evaluated through course feedback questionnaires, analysis of theoretical test scores, evaluations of the trainees administering and receiving anesthesia on the current anesthesia, and faculty evaluations of the success of the anesthesia, and t-tests and chi-square tests were performed using SPSS 23.0.Results:There was no significant difference in baseline level between the two groups. The students in the experimental group thought that the learning was more vivid ( t=4.24, P=0.005) and had more self-confidence in local anesthesia ( t=4.99, P<0.001). The students in the experimental group felt less needle tip jitter during injection ( t=2.22, P=0.048) and better contact with the medial surface of the mandible ( t=2.22, P=0.020). The students who received anesthesia reported less pain during injection ( t=1.99, P=0.029) and better anesthesia of the inferior alveolar nerve ( t=3.36, P=0.039) in the experimental group. Teacher assessment revealed that the experimental group had a significantly lower failure rate of inferior alveolar nerve block than the control group ( χ2=4.40, P=0.036). Conclusions:The virtual simulation system can optimize the experimental teaching of oral local nerve block anesthesia and can achieve a satisfactory teaching effect.

Network meta-analysis of the modeling effects of different factors on rabbit models of steroid-induced osteonecrosis of femoral head / 中国组织工程研究

OBJECTIVE:The rabbit model of steroid-induced osteonecrosis of femoral head is the most commonly used animal model of femoral head necrosis.The pathological changes of the femoral head are close to clinical practice,however,the conditions,methods and evaluation standards of animal models reported in and outside China are not uniform,which leads to the low scientific value of animal models and is difficult to popularize.This study aimed to clarify the influence of different mold-making conditions on the establishment of steroid-induced osteonecrosis of femoral head rabbit model and analyze the appropriate conditions for the successful model establishment. METHODS:We searched the CNKI,WanFang,VIP,CBM,WoS,PubMed and EMbsae databases for the literature on the modeling of steroid-induced osteonecrosis of femoral head rabbits up to April 1,2022,completed the screening of the literature according to the inclusion and exclusion criteria and literature quality evaluation,and extracted the outcome index data in the literature.RevMan Stata and ADDIS statistical software were used to conduct a meta-analysis of the included data. RESULTS:(1)A total of 82 articles with 1 366 rabbits were included in the study.The steroid-induced osteonecrosis of femoral head modeling methods were divided into three types:steroid-alone method,steroid combined lipopolysaccharide method and steroid combined serum method.Among these,33 articles used steroid-alone method;20 articles used steroid combined lipopolysaccharide method;29 articles used steroid combined serum method.(2)Meta-analysis results showed that the three modeling methods significantly increased the rate of empty bone lacunae in the femoral head of steroid-induced osteonecrosis of femoral head rabbits(P<0.001),and significantly decreased the ratio of the trabecular bone area in the femoral head of steroid-induced osteonecrosis of femoral head rabbits(P<0.001).The order of empty bone lacunae rate of each modeling method was:steroid combined with lipopolysaccharide method>steroid-alone method>steroid combined with serum method>normal group,and the order of trabecular bone area rate of each modeling method was:normal group>steroid combined with serum method>steroid-alone method>steroid combined with lipopolysaccharide method.(3)The results of subgroup analysis suggested that the rate of empty bone lacunae in the rabbit model induced by steroid alone might be related to the rabbit variety and the type of steroid used for modeling(difference between groups P<0.05),in which the combined effect amount of New Zealand white rabbits was higher than that of Chinese white rabbits(P<0.05)and Japanese white rabbits,and the combined effect amount of dexamethasone was higher than that of other steroids.The rate of empty bone lacunae induced by steroid combined with lipopolysaccharide was related to the administration mode of lipopolysaccharide and the type of steroid(P<0.05),among which the combined effect of methylprednisolone sodium succinate was significantly higher than that of other steroids(P<0.05),and the combined effect of prednisolone was significantly lower than that of other steroids(P<0.05).The combined effect of lipopolysaccharide 100 μg/kg×twice was significantly lower than 10 μg/kg×twice and 50 μg/kg×twice(P<0.05).The rate of empty bone lacunae in the model induced by steroid combined with serum was related to serum dose and steroid type(P<0.05),among which the combined effect amount of dexamethasone sodium phosphate was significantly higher than other steroid types(P<0.05),and the combined effect amount of dexamethasone was significantly lower than other steroid types(P<0.05);the combined effect amount of serum"10 mL/kg+6 mL/kg"combined dose was lower than other serum doses(P<0.05). CONCLUSION:(1)With the rate of empty bone lacunae and the ratio of trabecular bone area as the judgment standard for the successful establishment of the model,the three modeling methods can successfully construct the rabbit steroid-induced osteonecrosis of femoral head model,of which the steroid combined with lipopolysaccharide method is the best.(2)New Zealand white rabbits and dexamethasone are recommended when selecting the steroid-alone method.Methylprednisolone sodium succinate and low-dose lipopolysaccharide are recommended when selecting the steroid combined with lipopolysaccharide method.Dexamethasone sodium phosphate is recommended when selecting the steroid combined with serum modeling method.

Effects of long noncoding RNA-NRON on apoptosis following myocardial infarction in mice / 中国医科大学学报

Objective To investigate the effects of long noncoding RNA(lncRNA)-NRON on apoptosis following myocardial infarc-tion(MI)in mice.Methods The C57BL/6 mice were randomly divided into four groups:sham operation(Sham)group,MI group,MI combined with lncRNA-NRON interference lentivirus(MI+shNRON)group,and MI combined with the negative control(NC)lentivirus(MI+NC)group.The expression of lncRNA-NRON was detected using real-time PCR.In addition,the pathology of the myocardial tissue injury was analyzed using HE staining,the myocardial infarction size was examined using TTC staining,and the extent of apoptosis was assessed using the TUNEL assay,respectively.The RPISeq database was used to predict the probability of interaction between lncR-NA-NRON and the voltage-dependent anionic channel protein(VDAC).The effect of lncRNA-NRON on the expression of VDAC protein was detected using Western blotting.Results The lncRNA-NRON expression was significantly increased in the MI group,and the tar-geted knockdown of lncRNA-NRON resulted in alleviation of the pathological myocardial tissue injury,reduction in the myocardial infarc-tion area,and inhibition of apoptosis.The probability of interaction between lncRNA-NRON and VDAC reached 0.9,indicating a high probability of their association.Additionally,lncRNA-NRON could regulate the protein expression of VDAC.Conclusion Knockdown of lncRNA-NRON could reduce the occurrence of myocardial injury following myocardial infarction.This effect may be attributable to a spe-cific mechanism wherein lncRNA-NRON affects the process of apoptosis by binding to VDAC,consequently suppressing its expression.

Development of a new type of detection window protective device for surface contamination monitor / 中国医学装备

Objective:To develop a new type of detection window protective device for surface contamination monitor,and to verify its testing effect.Methods:The new type of surface contamination monitor detection window protection device was composed of the protective film and fixed frame,which was of integrated design and one-off production.The protective film was made of transparent flat Myra film,thickness≤2.5μm,the fixed frame was a rectangular hollow structure surrounded by four edges and provided with a working surface and a mounting surface.The protective film was pasted on the inner wall of the working surface of the fixed frame by adhesive,and the protective film and fixed frame were installed on the outside of the detection window of the surface contamination monitor by means of fixing buckles.Two commonly used surface contamination detection instruments,RDa150 and Como170,were selected to measure artificial radiation sources under three protection states:no film protection,plastic wrap protection and new protection device to test the detection efficiency and operability of the new surface contamination monitor's detection window protection device.Results:Compared with the traditional protective measures of plastic wrap,the detection efficiency of α,β and γ rays was more effectively ensured by the new detection window protective device for surface contamination monitor,and the detection efficiency of α rays was increased from about 40%to about 70%.Conclusion:The new detection window protection device for surface contamination monitor can significantly improve the detection efficiency of radioactive contamination,especially alpha-ray pollution,and effectively protect the instrument and equipment,and effectively improve the detection efficiency of surface contamination detection operators.

Implementation Strategy Analysis of Clinical Pathway in Large Public Hospitals under DRG Payment Reform / 中国医院管理

Clinical pathway has great similarity with DRG,and plays an important role in standardizing diagnosis and treatment behavior and controlling medical expenses.Based on the analysis of the relationship between DRG payment method reform and clinical pathway,taking a public hospital in Wuhan City,Hubei Province as an example,the clinical pathway implementation strategy of large public hospitals under the DRG payment method reform was explored from five aspects:management system,suitable disease types,doctor's order setting,information system,training and assessment.

Study on the current status of dental caries in preschool children in Chongming District， Shanghai / 上海预防医学

ObjectiveTo investigate the prevalence of dental caries among preschool children in Chongming District， Shanghai， and to analyze the related factors influencing dental caries in preschool children in Chongming District， in order to provide references and suggestions for the prevention of dental caries in preschool children in Chongming District. MethodsFrom January to April 2022， 939 preschool children from 5 kindergartens in Chongming District of Shanghai were selected as the research objects through random cluster sampling. The dental caries prevalence rate and related risk factors of dental caries in preschool children were studied through oral examinations and questionnaire surveys. ResultsThe prevalence rate of dental caries among the 939 preschool children was 45.69%. The prevalence of dental caries in preschool children was not related to gender but increased with age （P<0.001）. Risk factors for dental caries in children included consuming desserts between meals or before bedtime （OR=3.049， P<0.001）， consuming sugared milk （OR=2.389， P=0.027）， presence of dental caries in caregivers （OR=1.888， P<0.001）， age （OR=1.758， P<0.001）， regular consumption of certain beverages by children （OR=1.250， P=0.029）， and the frequency of snack consumption （OR=1.191， P=0.034）. ConclusionTo reduce the incidence of dental caries in preschool children， it is recommended that caregivers undergo oral health examinations and dental caries treatment to reduce the transmission of cariogenic bacteria. Additionally， reducing the frequency of children’s consumption of snacks， sugary drinks， and dairy products， and avoiding unhealthy eating habits such as consuming desserts before bedtime are advised. It is also important to educate children on proper toothbrushing methods to ensure the effectiveness of toothbrushing and to encourage them to develop good oral hygiene habits.

Transformation of dominant eye after small incision lenticule extraction and its effect on visual quality / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To analyze the changes of the dominant eye in myopic patients after small incision lenticule extraction(SMILE)and its effect on visual quality.METHODS: Prospective clinical study. A total of 140 patients(280 eyes)who underwent SMILE operation to correct myopia in the First Affiliated Hospital of Xinjiang Medical University from June to December 2022 were selected. They were divided into dominant eye transformation group(46 cases, 92 eyes)and non-transformation group(94 cases, 188 eyes)according to whether the dominant eye transformation occurred during the follow-up in postoperative 3 mo. The uncorrected visual acuity(UCVA)of the two groups was evaluated, the subjective visual quality was evaluated by the quality of life impact of refractive correction(QIRC)scale, and the objective visual quality was evaluated by measuring the high-order aberrations of the whole eye before and at 1 and 3 mo after surgery.RESULTS: Before SMILE, the right type of dominant eye was 105 cases, left-type was 35 cases. There were 46 cases had change at 1 mo postoperatively, and there was no new change at 3 mo after operation than 1 mo after operation. There was no significant difference in UCVA and QIRC scale score between the two groups preoperatively and at 1 and 3 mo postoperatively(P&#x003E;0.05). Comparison of the dominant eye between the two groups: the total higher-order aberrations and spherical aberrations at 3 mo postoperatively were significantly higher than those in the non-transformed group(P=0.030, 0.046); Comparison of the non-dominant eye between the two groups: trefoil in the transformed group at 1 mo postoperatively was significantly higher than that in the non-transformed group(P=0.008). The binocular difference of trefoil in the transition group was significantly higher than that in the non-transition group at 1 mo after surgery(P=0.022), with no differences in the rest parameters.CONCLUSION: Some patients may experience a change in the dominant eye after SMILE surgery, with no significant impact on subjective visual quality. The decrease of objective visual quality in the early postoperative period may be an associated factor in the dominant eye transformation.

Application Study of Enzyme Inhibitors and Their Conformational Optimization in The Treatment of Alzheimer’s Disease / 生物化学与生物物理进展

Alzheimer’s disease (AD) is a central neurodegenerative disease characterized by progressive cognitive dysfunction and behavioral impairment, and there is a lack of effective drugs to treat AD clinically. Existing medications for the treatment of AD, such as Tacrine, Donepezil, Rivastigmine, and Aducanumab, only serve to delay symptoms and but not cure disease. To add insult to injury, these medications are associated with very serious adverse effects. Therefore, it is urgent to explore effective therapeutic drugs for AD. Recently, studies have shown that a variety of enzyme inhibitors, such as cholinesterase inhibitors, monoamine oxidase (MAO)inhibitors, secretase inhibitors, can ameliorate cholinergic system dysfunction, Aβ production and deposition, Tau protein hyperphosphorylation, oxidative stress damage, and the decline of synaptic plasticity, thereby improving AD symptoms and cognitive function. Some plant extracts from natural sources, such as Umbelliferone, Aaptamine, Medha Plus, have the ability to inhibit cholinesterase activity and act to improve learning and cognition. Isochromanone derivatives incorporating the donepezil pharmacophore bind to the catalytic active site (CAS) and peripheral anionic site (PAS) sites of acetylcholinesterase (AChE), which can inhibit AChE activity and ameliorate cholinergic system disorders. A compound called Rosmarinic acid which is found in the Lamiaceae can inhibit monoamine oxidase, increase monoamine levels in the brain, and reduce Aβ deposition. Compounds obtained by hybridization of coumarin derivatives and hydroxypyridinones can inhibit MAO-B activity and attenuate oxidative stress damage. Quinoline derivatives which inhibit the activation of AChE and MAO-B can reduce Aβ burden and promote learning and memory of mice. The compound derived from the combination of propargyl and tacrine retains the inhibitory capacity of tacrine towards cholinesterase, and also inhibits the activity of MAO by binding to the FAD cofactor of monoamine oxidase. A series of hybrids, obtained by an amide linker of chromone in combine with the benzylpiperidine moieties of donepezil, have a favorable safety profile of both cholinesterase and monoamine oxidase inhibitory activity. Single domain antibodies (such as AAV-VHH) targeted the inhibition of BACE1 can reduce Aβ production and deposition as well as the levels of inflammatory cells, which ultimately improve synaptic plasticity. 3-O-trans-p-coumaroyl maslinic acid from the extract of Ligustrum lucidum can specifically inhibit the activity of γ-secretase, thereby rescuing the long-term potentiation and enhancing synaptic plasticity in APP/PS1 mice. Inhibiting γ-secretase activity which leads to the decline of inflammatory factors (such as IFN-γ, IL-8) not only directly improves the pathology of AD, but also reduces Aβ production. Melatonin reduces the transcriptional expression of GSK-3β mRNA, thereby decreasing the levels of GSK-3β and reducing the phosphorylation induced by GSK-3β. Hydrogen sulfide can inhibitGSK-3β activity via sulfhydration of the Cys218 site of GSK-3β, resulting in the suppression of Tau protein hyperphosphorylation, which ameliorate the motor deficits and cognitive impairment in mice with AD. This article reviews enzyme inhibitors and conformational optimization of enzyme inhibitors targeting the regulation of cholinesterase, monoamine oxidase, secretase, and GSK-3β. We are hoping to provide a comprehensive overview of drug development in the enzyme inhibitors, which may be useful in treating AD.

Research progress on the intervention of traditional Chinese medicine in renal interstitial fibrosis based on PI3K/Akt signaling pathway / 中国药房

Renal interstitial fibrosis（RIF） is the main pathological manifestation of chronic kidney disease. Due to the complexity of the mechanism， there is no specific treatment for RIF in clinical practice. The abnormal activation of the phosphatidylinositol 3-kinase （PI3K）/protein kinase B（Akt） signaling pathway and the activation of downstream target genes are key drivers of RIF induction and progression. Traditional Chinese medicine has the characteristics of precise efficacy and minimal toxic side effects， and the occurrence and development of RIF can be regulated by multiple targets and mutual coordination. This review focuses on the PI3K/Akt signaling pathway and summarizes the potential targets and regulatory mechanisms of traditional Chinese medicine in the treatment of RIF. It is found that various effective ingredients （such as sinomenine， mangiferin， coumarin derivates from Hydrangea paniculata， etc.） and formulas （such as Fushengong decoction， Qi-Bang-Yi-Shen formula， etc.） of traditional Chinese medicine can inhibit fibroblast proliferation， improve inflammation and oxidative stress， maintain mitochondrial stability， and slow down ferroptosis through this pathway， thereby delaying the occurrence and progression of RIF.

Quantitative analysis of differences in blood flow parameters in the macular area of healthy people of different ethnic groups in Xinjiang by OCTA / 国际眼科杂志(Guoji Yanke Zazhi)

AIM:To measure the superficial capillary plexus(SCP)vessel density(VD), deep capillary plexus(DCP)VD, and the area, circumference, and roundness index of the foveal avascular zone(FAZ)in healthy individuals of four ethnic groups, namely, Uyghur, Han, Kazakh, and Hui by optical coherence tomography angiography(OCTA), and to investigate the differences of blood flow parameters in macular area of healthy individuals among different ethnic groups in China.METHODS: A total of 80 cases(80 eyes)of healthy subjects if each of the four ethnic groups who went to the Eye Center of the Friendship Hospital of Ili Kazak autonomous Prefecture from December 2022 to March 2023 and met the criteria were selected for the study, with 320 eyes totally. The patients were grouped and numbered according to their ethnicity, and the spherical equivalent and axial length were obtained by using an autorefractor and IOL Master. The blood flow images of the macular area in the range of 3 mm×3 mm were obtained by using a DRI Triton OCT detector, and the images were analyzed by using the built-in IMAGENET6 software to obtain the blood flow parameters. Furthermore, the differences in the blood flow parameters between different ethnic groups as well as the effects of gender, age, and axial length on macular blood flow parameters of different ethnic groups were compared.RESULTS:There were no statistically significant differences in gender, age, axial length, diopter, and image quality(IQ)among the four groups of subjects(all P&#x003E;0.05). Ethnic differences: in SCP, Uyghur inferior VD is higher than Kazakh, Hui inferior VD is higher than Han and Kazakh, Han and Hui nasal VD is higher than Uyghur, Kazakh foveal VD is higher than Han and Hui, Kazakh FAZ area is smaller than the other 3 ethnic groups, Han and Hui FAZ perimeter is larger than Kazakh, and Hui FAZ circularity index is lower than the other 3 ethnic groups; in DCP, Uyghur foveal VD is higher than Han and Hui, Kazakh foveal VD is higher than Han and Hui, Kazakh FAZ area and perimeter are smaller than the other 3 ethnic groups and Kazakh FAZ circularity index is higher than the other 3 ethnic groups(all P&#x003C;0.05). Sex differences: in SCP, FAZ area and perimeter of Han females were larger than those of males, and FAZ circularity index of Hui females was higher than that of males(all P&#x003C;0.05); in DCP, parafoveal VD and whole VD in females of all four ethnic groups were higher than those of males(all P&#x003C;0.05). Age correlation: in SCP, age was negatively correlated with the FAZ circularity index of Kazakh; in DCP, age was negatively correlated with the parafoveal and the whole VD of Han, Kazakh, and Hui(all P&#x003C;0.05). Axial length correlation: in SCP, the axial length was negatively correlated with Kazakh and Hui foveal VD, Hui parafoveal VD, Uyghur, Kazakh and Hui whole VD, and positively correlated with Kazakh FAZ area and perimeter; in DCP, the axial length was negatively correlated with Uyghur, Kazakh, Hui foveal VD, Hui whole VD, and positively correlated with Kazakh and Hui FAZ area and perimeter(all P&#x003C;0.05).CONCLUSION:There were differences in macular blood flow parameters among the Uyghur, Han, Kazakh, and Hui populations, with the area and perimeter of the FAZ of the Kazakh significantly smaller than those of the other three ethnic groups. Gender, age, and axial length are also related to macular blood flow parameters.

Interval training effects on cardiorespiratory capacity of swimmers / Efeito do treinamento intervalado sobre a capacidade cardiorrespiratória de nadadores / Efecto del entrenamiento por intervalos en la capacidad cardiorrespiratoria de nadadores

ABSTRACT Introduction: Cardiopulmonary function is directly related to the body's ability to perform metabolism under aerobic conditions. It is a key characteristic for the training of professional swimmers. It is believed that adding interval training to traditional workouts may contribute to the aerobic endurance of these athletes. Objective: Evaluate the interval training effects on the cardiorespiratory capacity of swimmers. Methods: Twenty volunteer swimmers were randomly divided into two groups for seven weeks. There were 4 hours of class per week, totaling 28 hours of training. In the formal training stage, the experimental group performed intermediate-intensity training, while the control group continued to perform traditional swim team training. The experimental indicators pertinent to the evaluated athletes were collected, tested, and analyzed before and after the experiment. Results: The VO2 of the athletes in the experimental group increased from 3.90±0.67L/min before the experiment to 4.06±0.73L/min after the experiment; VE increased from 156.08±35.76L before the experiment to 180.08±39.42L after the experiment; underwater endurance time increased from 46.80±8.43s before the experiment to 55.49±7.60s after the experiment. Conclusion: Intermittent training improves athletes' physical fitness and sports capacity, being an effective method to improve cardiopulmonary function. Level of evidence II; Therapeutic studies - investigation of treatment outcomes.

RESUMO Introdução: A função cardiopulmonar está diretamente relacionada à capacidade do organismo de executar a metabolização sob condições aeróbicas. É uma característica chave para os treinamentos de nadadores profissionais e acredita-se que a adição do treinamento intervalado nos treinos tradicionais possa contribuir à resistência aeróbica desses atletas. Objetivo: Avaliar o efeito do treinamento intervalado sobre a capacidade cardiorrespiratória dos nadadores. Métodos: Vinte nadadores voluntários foram divididos aleatoriamente em dois grupos durante 7 semanas. Foram 4 horas de aula por semana, totalizando 28 horas de treino. Na etapa de treinamento formal, o grupo experimental realizou essencialmente o treinamento de intensidade intermediária, enquanto o grupo de controle permaneceu executando o treinamento tradicional da equipe de natação. Os indicadores experimentais pertinentes aos atletas avaliados foram coletados, testados e analisados antes e depois do experimento. Resultados: O VO2 dos atletas do grupo experimental aumentou de 3,90±0,67L/min antes do experimento para 4,06±0,73L/min após o experimento; o VE aumentou de 156,08±35,76L antes do experimento para 180,08±39,42L após o experimento; o tempo de resistência subaquática aumentou de 46,80±8,43s antes do experimento para 55,49±7,60s após o experimento. Conclusão: O treinamento intermitente contribui para melhorar a aptidão física e a capacidade esportiva dos atletas, sendo um método eficaz no aprimoramento da função cardiopulmonar. Nível de evidência II; Estudos terapêuticos - investigação dos resultados do tratamento.

RESUMEN Introducción: La función cardiopulmonar está directamente relacionada con la capacidad del organismo para realizar el metabolismo en condiciones aeróbicas. Es una característica clave para los entrenamientos de los nadadores profesionales y se cree que la adición del entrenamiento interválico en los entrenamientos tradicionales puede contribuir a la resistencia aeróbica de estos atletas. Objetivo: Evaluar el efecto del entrenamiento por intervalos sobre la capacidad cardiorrespiratoria de los nadadores. Métodos: Veinte nadadores voluntarios fueron divididos aleatoriamente en dos grupos durante 7 semanas. Se impartieron 4 horas de clase a la semana, totalizando 28 horas de entrenamiento. En la etapa de entrenamiento formal, el grupo experimental realizó esencialmente un entrenamiento de intensidad intermedia, mientras que el grupo control permaneció realizando el entrenamiento tradicional del equipo de natación. Los indicadores experimentales pertinentes a los atletas evaluados fueron recogidos, testados y analizados antes y después del experimento. Resultados: El VO2 de los atletas del grupo experimental aumentó de 3,90±0,67L/min antes del experimento a 4,06±0,73L/min después del experimento; el VE aumentó de 156,08±35,76L antes del experimento a 180,08±39,42L después del experimento; el tiempo de resistencia subacuática aumentó de 46,80±8,43s antes del experimento a 55,49±7,60s después del experimento. Conclusión: El entrenamiento por intervalos contribuye a mejorar la forma física y la capacidad deportiva de los atletas, siendo un método eficaz para mejorar la función cardiopulmonar. Nivel de evidencia II; Estudios terapéuticos - investigación de los resultados del tratamiento.

Protective Effect of Jianpi Huogu Prescription on Functional Injury of Vascular Endothelial Cells Caused by Alcohol Based on Akt/JNK/p38 MAPK Signaling Pathway / 中国实验方剂学杂志

ObjectiveTo investigate the protective effect of Jianpi Huogu prescription （JPHGP） on the functional injury of vascular endothelial cells caused by alcohol and explore its mechanism based on protein kinase B/c-Jun amino-terminal kinase/p38 MAPK （Akt/JNK/p38 MAPK） signaling pathway. MethodThrough chick embryo allantoic membrane， thoracic aortic ring， and migration， invasion， adhesion， and lumen formation of human umbilical vein endothelial cells （HUVEC）， the effect of JPHGP with different concentrations （8， 16 and 32 μg·L-1） on angiogenesis was observed in the presence or absence of alcohol. The expression levels of phosphorylation of Akt， JNK， and p38 MAPK were determined by Western blot. ResultAs compared with the normal group， the number and length of capillaries around the arterial ring in the model group were decreased， and the migration， invasion， and lumen formation capacity of HUVEC were decreased （P<0.05， P<0.01）. After treatment with 16 and 32 μg·L-1 JPHGP， the length of neovascularization in chick embryo allantoic membrane was significantly increased （P<0.05， P<0.01）. Compared with the model group， the 8， 16， and 32 μg·L-1 JPHGP groups increased the number of capillaries around the thoracic aortic ring in a concentration-dependent manner （P<0.05， P<0.01）， and the 32 μg·L-1 JPHGP group increased the length of capillaries around the thoracic aortic ring （P<0.05）. The 16 and 32 μg·L-1 JPHGP groups enhanced the migration， invasion， and lumen formation capacity of HUVEC. The results of Western blot showed that， as compared with the normal group， the protein expression levels of p-JNK/JNK， p-p38 MAPK/p38 MAPK， and p-Akt/Akt were significantly decreased in the model group （P<0.01）， and as compared with the model group， the protein expression levels of p-p38 MAPK/p38 MAPK and p-Akt/Akt were significantly increased in the 8， 16， and 32 μg·L-1 JPHGP groups （P<0.01） and the protein expression level of p-JNK/JNK was increased significantly in the 16 and 32 μg·L-1 JPHGP groups （P<0.01）. ConclusionJPHGP has a protective effect on the functional injury of vascular endothelial cells caused by alcohol， and its mechanism may be related to the activation of Akt/JNK/p38 MAPK signaling pathway. Relevant research results will provide certain scientific basis for clarifying the effect of JPHGP on 'invigorating spleen and promoting blood circulation'.

Anti-swelling and Analgesic Mechanism of Jianpi Tongluo Prescription from MAPKs Signaling Pathway / 中国实验方剂学杂志

ObjectiveTo observe the anti-swelling and analgesic effects of Jianpi Tongluo prescription （JPTL） and to explore its mechanism initially. MethodA total of 120 ICR mice were divided into normal group， model group， JPTL low-， medium- and high-dose groups （5， 10， 20 g·kg-1） and positive drug （celecoxib， 0.03 g·kg-1） group， with 10 in each group （po，once a day）. Complete freund's adjuvant （CFA） was used to induce the model of chronic inflammatory pain， and xylene-induced ear swelling test， hot plate test and acetic acid writhing test were performed to observe the anti-swelling and analgesic effects of different doses of JPTL in these four acute and chronic models. Further， enzyme-linked immunosorbent assay （ELISA） was used to detect the expressions of prostaglandin E2 （PGE2）， interleukin-1β （IL-1β）， interleukin-6 （IL-6） and tumor necrosis factor-α （TNF-α） in serum and inflammatory paw of mice with chronic inflammatory pain， and the expressions of aquaporin 1 （AQP1）， aquaporin 3 （AQP3）， cyclooxygenase 1 （COX1）， cyclooxygenase 2 （COX2） and mitogen-activated protein kinases （MAPKs） in inflammatory paw were detected by Western blot， to explore the preliminary mechanism of JPTL. ResultCompared with the conditions in the normal group， there was a significant increase in the ear swelling of xylene-induced model mice， a shortened paw withdrawal latency in the hot plate test （P<0.01）. Compared with the model group， JPTL remarkably increased the inhibition rate of xylene-induced ear swelling （P<0.05， P<0.01）， prolonged the latency period of writhing caused by acetic acid and reduced the number of writhing （P<0.05， P<0.01）. Compared with normal group, the degree of feet swelling in chronic inflammatory pain mice was significantly increased， the threshold of mechanical pain was decreased and the threshold of cold pain was increased （P<0.05， P<0.01）， the protein contents of AQP1 and AQP3 in inflammatory feet were increased， and the contents of IL-1β， IL-6， TNF-α， PGE2 and COX2 in inflammatory feet were increased in serum and/or inflammatory feet. The protein expression levels of p-p38 MAPK， p-JNK and p-ERK in inflammatory feet were increased （P<0.01）. Compared with the model group， JPTL relieved paw swelling of mice with chronic inflammatory pain， elevated mechanical withdrawal threshold while decreased cold withdrawal threshold， with analgesia lasting for 4 h and the optimal time point for analgesia being 2 h after administration （P<0.05， P<0.01）. Moreover， JPTL down-regulated AQP1， AQP3， COX2， p-p38 MAPK， p-JNK and p-ERK in inflammatory paw of mice with chronic inflammatory pain and reduced IL-1β， IL-6， TNF-α， and PGE2 in serum and/or inflammatory paw， but it had no significant effect on COX1 （P<0.05， P<0.01）. ConclusionJPTL has anti-swelling and analgesic effects， and its mechanism is related to inhibiting the production of cytokines and inflammatory mediators via the down-regulation of MAPKs signaling pathway， which provides an experimental basis for the clinical application of JPTL.

Analysis on death of children under 5 years in Chongming District， Shanghai from 2011 to 2020 / 上海预防医学

ObjectiveTo analyze the mortality data of children under 5 years in Chongming District， Shanghai， and to analyze the main causes of death of children under 5 years， so as to provide scientific basis for reducing the mortality of children under 5 years in Chongming District. MethodsData of children under 5 years in Chongming District from 2011 to 2020 were collected from the Maternal and Child Health Information System of Chongming District， Shanghai. The mortality rate and main causes of death of children under 5 years in Chongming District were analyzed retrospectively. ResultsFrom 2011 to 2020， the average mortality rate of children under 5 years in Chongming District was 6.51‰， and the overall trend was stable. The mortality rate of children under 5 years with non-local household registration （11.44‰） was significantly higher than that of children under 5 years of age with local household registration （4.88‰） （P<0.05）. The main causes of death for children under 5 years were accidental deaths （drowning， accidental asphyxia， traffic accidents）， while the main causes of death for infants were congenital heart disease， premature birth or low birth weight， congenital abnormalities， birth asphyxia and pneumonia. ConclusionIt is necessary to strengthen safety education for children and their guardians and strengthen safety management for children who are not registered in this city. Departments of obstetrics and gynecology and the departments of pediatrics should be expanded， and prenatal examination should be strenthened for high risk or elderly parturient women to further reduce the death rate of children under 5 years old.

Shuyuwan Regulates M1/M2 Polarization of Tumor-associated Macrophages to Inhibit Progression of Colorectal Cancer / 中国实验方剂学杂志

ObjectiveTo explore the molecular mechanism of Shuyuwan regulating polarization of tumor-associated macrophages （TAMs） to inhibit the progression of colorectal cancer （CRC）. MethodThe nude mouse model of orthotopic transplantation of colon cancer was established. Male BALB/c-nu nude mice （n=28， 4 weeks old） were randomly assigned into 4 groups （n=7）： Model group （normal saline） and low-， medium-， and high-dose （1.725， 2.310， 2.895 g·kg-1·d-1， respectively） Shuyuwan groups. On day 9 after the tumor block was inoculated， the mice were administrated by gavage with corresponding agents at a dose of 15 mL·kg-1 once a day， 6 days a week， and no agent on the 7th day. After two consecutive weeks of intervention， the nude mice were sacrificed and the tumor samples were collected. A part of the colon tissue and the tumor tissue was used to prepare sections， and hematoxylin-eosin （HE） staining was performed for pathological observation. The expression of inducible nitric oxide synthase （iNOS） and arginase-1 （Arg-1） in the tumor tissue was detected by immunohistochemistry （IHC）. The mRNA levels of interleukin-12 （IL-12）， epidermal growth factor （EGF）， and transforming growth factor-β1 （TGF-β1） in the tumor tissue were determined by Real-time polymerase chain reaction （PCR）. Western blot was employed to determine the protein levels of iNOS， IL-12， EGF， and TGF-β1 in the tumor tissue. ResultCompared with the model group， Shuyuwan inhibited the growth of colon cancer cells in nude mice and caused the tumor cell necrosis in different degrees. The high-dose Shuyuwan group had the strongest inhibitory effect on the growth of tumor cells， which basically lost the normal morphology. Furthermore， Shuyuwan up-regulated the expression of iNOS and IL-12 in M1-type macrophages （P<0.05） and down-regulated the expression of Arg-1， EGF， and TGF-β1 in M2-type macrophages （P<0.05）， which indicated the weakened polarization of macrophages toward M2 type and the enhanced polarization toward M1 type after treatment with Shuyuwan. ConclusionShuyuwan can inhibit the growth of orthotopically transplanted colon tumor by blocking the polarization of TAMs to M2 type and promoting the polarization of TAMs to M1 type.

Comparative study on pathological characteristics of four different antigen-induced rheumatoid arthritis mouse models / 药学学报

Rheumatoid arthritis (RA) is an autoimmune disease driven by antigens and mediated by T cells. Collagen II (CII) and fibrinogen (Fib) are the two main antigens in the pathogenesis of RA. The antigen produced after citrulline modification (Cit) is also one of the inducements to induce the body to produce a pathogenic anti-citrulline protein antibody (ACPA). To provide a reference for RA-related research, this study intends to establish an RA animal model by using CII, Cit-CII, Fib, and Cit-Fib antigens, emulsification with complete Freund's adjuvant and immunization with DBA/1 mice, respectively, to compare the pathological characteristics of RA models induced by different antigens from the aspects of pathology, imaging and serum biochemistry. Animal welfare and experimental process are in accordance with the regulations of the Experimental Animal Ethics Committee of the China Academy of Chinese Medical Sciences. The results showed that the CII, Cit-CII, and Cit-Fib induced mice all had symptoms such as joint redness and swelling, and toe deformation and the clinical score and incidence rate were higher than those of the normal group. The CII group had the most serious lesions, with a incidence rate of 100%, and the Cit-CII and Cit-Fib groups had mild symptoms, with a incidence rate of 25% and 37.5%, respectively; pathological and imaging examination results showed that the joints of mice in CII-induced group showed severe synovial inflammation, cartilage and bone destruction, while those in Cit-CII and Cit-Fib group showed only slight inflammatory infiltration, joint cavity stenosis and bone destruction; the results of serum antibody detection showed that CII, Cit-CII and Cit-Fib groups all produced high levels of anti-cyclic citrullinated peptide (CCP) antibodies, among which, Cit-Fib group > Cit-CII group > CII group > Fib group, and both Cit-CII and Cit-Fib groups produced high levels of citrullinated epitope-specific antibodies, while the total IgG level was the highest in CII group; serum ELISA and RT-PCR analysis of joint tissue showed that the expression of pro-inflammatory factors and bone destruction-related molecules increased most significantly in the CII-induced group, followed by Cit-Fib and Cit-CII. The above results showed that among the four different antigens, the symptoms and conditions of arthritis in RA mice induced by CII were the most serious, and IgG instead of anti-CCP antibody was its typical immunological feature, and CII could be the first choice for the model of RA mice; Cit-Fib has certain immunogenicity, can partially induce the symptoms and conditions of RA arthritis in mice, and produce high-level anti-CCP antibody and anti-Cit-Fib antibody, which is more suitable for the study of citrulline-related RA; although Cit-CII has certain immunogenicity, the incidence, and severity of RA arthritis induced by Cit-CII in mice are low.

From the body-mind holism to psychosomatic medicine: theory and practice of acupuncture and moxibustion / 中国针灸

The traditional life concept of "body-mind holism" in Chinese medicine has drawn a special attention with the development of modern psychosomatic medicine. The "body-mind holism" is valuable in the guidance for clinical acupuncture practice, but, it is only remained on the theoretical significance by the medical masters in the past dynasties. In the paper, based on the understanding of Huangdi Neijing (Yellow Emperor's Internal Classic), the similarities and differences are compared between the body-mind theory and psychosomatic medicine. In association with clinical observation, from three aspects, i.e. body-mind pathogenesis, acupoint detection and observing the mind, and body-mind treatment, the guidance of "body-mind holism" is explored for the clinical diagnosis and treatment of acupuncture and moxibustion; the referents of "body" and "mind" are clarified in views of disease, diagnosis and treatment; and the treatment strategies of acupuncture and moxibustion are discussed in the perspective of "body-mind holism".

Reverse effect of Semaphorin-3F on rituximab resistance in diffuse large B-cell lymphoma via the Hippo pathway / 中华医学杂志(英文版)

BACKGROUND@#Exploring the underlying mechanism of rituximab resistance is critical to improve the outcomes of patients with diffuse large B-cell lymphoma (DLBCL). Here, we tried to identify the effects of the axon guidance factor semaphorin-3F (SEMA3F) on rituximab resistance as well as its therapeutic value in DLBCL.@*METHODS@#The effects of SEMA3F on the treatment response to rituximab were investigated by gain- or loss-of-function experiments. The role of the Hippo pathway in SEMA3F-mediated activity was explored. A xenograft mouse model generated by SEMA3F knockdown in cells was used to evaluate rituximab sensitivity and combined therapeutic effects. The prognostic value of SEMA3F and TAZ (WW domain-containing transcription regulator protein 1) was examined in the Gene Expression Omnibus (GEO) database and human DLBCL specimens.@*RESULTS@#We found that loss of SEMA3F was related to a poor prognosis in patients who received rituximab-based immunochemotherapy instead of chemotherapy regimen. Knockdown of SEMA3F significantly repressed the expression of CD20 and reduced the proapoptotic activity and complement-dependent cytotoxicity (CDC) activity induced by rituximab. We further demonstrated that the Hippo pathway was involved in the SEMA3F-mediated regulation of CD20. Knockdown of SEMA3F expression induced the nuclear accumulation of TAZ and inhibited CD20 transcriptional levels via direct binding of the transcription factor TEAD2 and the CD20 promoter. Moreover, in patients with DLBCL, SEMA3F expression was negatively correlated with TAZ, and patients with SEMA3F low TAZ high had a limited benefit from a rituximab-based strategy. Specifically, treatment of DLBCL cells with rituximab and a YAP/TAZ inhibitor showed promising therapeutic effects in vitro and in vivo .@*CONCLUSION@#Our study thus defined a previously unknown mechanism of SEMA3F-mediated rituximab resistance through TAZ activation in DLBCL and identified potential therapeutic targets in patients.

Meta-analysis of Effect of Tripterygium wilfordii Polyglycoside Tablets Combined with Methotrexate and/or Leflunomide on Autoantibodies in Rheumatoid Arthritis / 中国实验方剂学杂志

ObjectiveTo evaluate the effect of Tripterygium wilfordii polyglycoside tablets （TWPT） combined with conventional synthetic disease-modifying antirheumatic drugs （csDMARDs） including methotrexate （MTX） and/or leflunomide （LEF） on autoantibodies in rheumatoid arthritis （RA） patients. MethodPubMed， EMBASE， Web of Science， Cochrane Library， China National Knowledge Infrastructure （CNKI）， VIP， Wanfang Data， and China Biomedical Literature Service System （SinoMed） were searched for randomized controlled trials （RCTs） of TWPT combined with MTX and/or LEF in the treatment of RA patients from database inception to December 1， 2021. Primary outcome indicators included rheumatoid factor （RF） and anti-citrullinated protein antibody （ACPA）， and secondary outcome indicators included immunoglobulin （IgA， IgG， and IgM） and adverse drug events （ADE）. ResultThirty-one RCTs， involving 2 643 adult patients， were included， including 20 RCTs of TWPT combined with MTX， 10 of TWPT combined with LEF， and one of TWPT combined with MTX and TWPT. The follow-up time ranged from two weeks to 13 months. Compared with csDMARDs alone， TWPT combined with other drugs significantly improved serum RF of RA patients ［SMD=-2.45， 95% CI ［-2.97， -1.93］， P<0.000 01］， anti-CCP ［SMD=-1.41， 95% CI （-2.35， -0.48）， P=0.003］， IgM ［SMD=-1.90， 95% CI （-3.03， -0.76）， P=0.001］， and IgA ［SMD=-1.18， 95% CI （-2.23， -0.12）， P=0.03］. There were no significant effects on IgG ［SMD=-1.02， 95% CI （-2.04， 0.01）， P=0.05］ and ADE ［RR=0.87， 95% CI （0.66， 1.15）， P=0.32］. ConclusionThe results of this study show that compared with csDMARDs alone， TWPT combined with csDMARDs can effectively improve the levels of autoantibodies in RA patients without increasing the incidence of ADE. However， due to the limited quality and quantity of the included RCTs， the relevant conclusions are only used as a reference for the clinical diagnosis and treatment of RA， and more high-quality studies are still needed to further confirm their efficacy.