Autologous ilium graft combination with titanium plate for sternal reconstruction: A case report / 中国胸心血管外科临床杂志

@#The sternum is the pivotal component of the thoracic cavity. It is connected with the clavicle and ribs on the upper part and both sides respectively, and plays an important role in protecting the stability of the chest wall. Sternal resection usually results in a large segmental chest wall defect that causes the chest wall to float and requires sternal reconstruction. This paper reports a 62 years male patient with thymic squamous cell carcinoma with sternal metastasis, who underwent thymotomy, sternal tumor resection and autologous lilum graft combined with sternal reconstruction by titanium plate after relevant examination was completed and surgical contraindications were eliminated. The patient was followed up for 6 months, the respiratory and motor functions were normal and the thoracic appearance was good.

Effects of intermittent soccer training on physical endurance in university students / Efeitos do treinamento intermitente com futebol sobre a resistência física de estudantes universitárias / Efectos del entrenamiento intermitente de fútbol en la resistencia física de estudiantes universitarias

ABSTRACT Introduction: The development of modern science and technology has led young people to a continuous decline in physical activity, negatively impacting the quality of cardiopulmonary endurance in college students. It is believed that the emerging need to strengthen physical endurance training can be met through sports. Progressive soccer training is a practice of interest due to its recreational and sporting effects. Objective: Study the effect of intermittent soccer training on the physical endurance of female college students. Methods: 12 classes of young women participated in soccer training lasting two hours, twice a week, according to the organization of the optional school soccer course. During the experiment, the intermittent training mode was selected and the combination of soccer walking and running was adopted for impact analysis. Results: The research showed that in the first 6 weeks, the changing trend of cardiopulmonary endurance of female college students was not different from that before the experiment, but there was a slight optimization phenomenon. After the experiment, the cardiopulmonary endurance of female college students was significantly improved. Conclusion: Intermittent soccer training for female college students can significantly improve their cardiorespiratory endurance and enhance their sports performance. It is an important tool for optimizing college students' physical functions and healthy growth. Level of evidence II; Therapeutic studies - investigation of treatment outcomes.

RESUMO Introdução: desenvolvimento da ciência e tecnologia modernas tem levado os jovens ao declínio contínuo da atividade física, impactando negativamente sobre a qualidade de resistência cardiopulmonar das estudantes universitárias. Acredita-se que a necessidade emergente de fortalecer o treinamento de resistência física possa ser suprida através do esporte. O treinamento progressivo de futebol é uma prática de interesse devido aos seus efeitos lúdicos e esportivos. Objetivo: Estudar o efeito do treinamento intermitente de futebol sobre a resistência física das estudantes universitárias. Métodos: 12 classes de jovens participaram do treinamento de futebol com duração de duas horas, no período de duas vezes por semana, de acordo com a organização do curso optativo de futebol escolar. Durante o experimento, o modo de treinamento intermitente foi selecionado e a combinação de marcha e corrida de futebol foi adotada para análise do impacto. Resultados: Os resultados da pesquisa mostraram que nas primeiras 6 semanas, a tendência de mudança de resistência cardiopulmonar das estudantes universitárias não era diferente da anterior à experiência, mas havia um leve fenômeno de otimização. Após o experimento, a resistência cardiopulmonar das estudantes universitárias foi significativamente aprimorada. Conclusão: O treinamento intermitente de futebol para estudantes universitárias pode aperfeiçoar significativamente sua resistência cardiorrespiratória e melhorar seu desempenho esportivo, sendo uma importante ferramenta para otimização das funções físicas e o crescimento saudável das estudantes universitárias. Nível de evidência II; Estudos terapêuticos - investigação dos resultados do tratamento.

RESUMEN Introducción: El desarrollo de la ciencia y la tecnología modernas ha llevado a los jóvenes a una disminución continua de la actividad física, lo que repercute negativamente en la calidad de la resistencia cardiopulmonar de los estudiantes universitarios. Se cree que la necesidad emergente de reforzar el entrenamiento de la resistencia física puede satisfacerse a través del deporte. El entrenamiento progresivo en fútbol es una práctica de interés por sus efectos lúdicos y deportivos. Objetivo: Estudiar el efecto del entrenamiento intermitente con fútbol sobre la resistencia física de estudiantes universitarias. Métodos: 12 clases de mujeres jóvenes participaron en entrenamientos de fútbol de dos horas de duración, dos veces por semana, según la organización del curso de fútbol escolar optativo. Durante el experimento, se seleccionó el modo de entrenamiento intermitente y se adoptó la combinación de fútbol caminando y corriendo para el análisis del impacto. Resultados: Los resultados de la investigación mostraron que en las primeras 6 semanas, la tendencia de cambio de la resistencia cardiopulmonar de las estudiantes universitarias no era diferente de la de antes del experimento, pero había un ligero fenómeno de optimización. Después del experimento, la resistencia cardiopulmonar de las estudiantes universitarias mejoró significativamente. Conclusión: El entrenamiento intermitente de fútbol para estudiantes universitarias puede mejorar significativamente su resistencia cardiorrespiratoria y mejorar su rendimiento deportivo, y es una herramienta importante para optimizar las funciones físicas y el crecimiento saludable de las estudiantes universitarias. Nivel de evidencia II; Estudios terapéuticos - investigación de los resultados del tratamiento.

Risk factors of new-onset hypertriglyceridemia in kidney transplant recipients: a single-center analysis / 器官移植

Objective To identify the risk factors of new-onset hypertriglyceridemia (HTG) in kidney transplant recipients. Methods Clinical data of 149 kidney transplant recipients were retrospectively analyzed. According to serum triglyceride (TG) level after operation, they were divided into the non-HTG group (TG≤1.7 mmol/L, n=60) and new-onset HTG group (TG>1.7 mmol/L, n=89). Baseline data of all recipients were compared between two groups. The risk factors of HTG in kidney transplant recipients were analyzed by generalized estimating equation (GEE), and validated by multiple regression equations. Results No significant differences were observed in baseline data between two groups (all P>0.05). Multivariate analysis showed that the incidence of HTG in the middle and high tacrolimus (Tac) concentration groups was higher than that in the low Tac concentration group [odds ratio (OR) 3.11, 95% confidence interval (CI) 1.22-7.93, P=0.018 in the middle Tac concentration group; OR 5.11, 95%CI 1.31-19.98, P=0.019 in the high Tac concentration group]. Compared with type-A blood recipients, the risk of new-onset HTG was significantly increased in type-O blood counterparts (OR 2.77, 95%CI 1.14-6.71, P=0.024). The risk of new-onset HTG was decreased along with the increase of preoperative globulin level (OR 0.93, 95%CI 0.87-0.99, P=0.043). At postoperative 3 months, Tac blood concentration in the new-onset HTG group was significantly higher compared with that in the non-HTG group, and significant difference was observed (P<0.05). Multiple regression equations confirmed that the risk of new-onset HTG in type-O blood kidney transplant recipients was higher than that in type-A blood counterparts, and the risk of new-onset HTG in the middle and high Tac concentration groups was higher than that in the low Tac concentration group (all P<0.05). Conclusions Type-O blood kidney transplant recipients are more prone to HTG. It is necessary to strengthen postoperative monitoring and control of blood lipids. The blood concentration of Tac probably affects the new-onset HTG in kidney transplant recipients. Maintaining an appropriate blood concentration of Tac may be beneficial to lowering the risk of HTG.

Erratum: Author correction to 'Mevalonate improves anti-PD-1/PD-L1 efficacy by stabilizing CD274 mRNA' Acta Pharmaceutica Sinica B 13 (2023) 2585-2600

[This corrects the article DOI: 10.1016/j.apsb.2023.04.002.].

RBMS3 Expression and Its Correlation with Clinicopathological Features and Prognosis of Epithelial Ovarian Cancer / 中山大学学报(医学科学版)

ObjectiveTo investigate the expression of RNA binding motif single stranded interacting protein 3 （RBMS3） in epithelial ovarian cancer （EOC） tissues and its relationship with the clinicopathological features and prognosis of EOC. MethodsThe study enrolled the paraffin-embedded tissues from 110 EOC cases and 73 benign epithelial ovarian tumor cases pathologically diagnosed in the first affiliated Hospital of Bengbu Medical College from January 2015 to December 2019. By using anti-RBMS3 polyclonal antibody， the immunohistochemical staining was employed to detect RBMS3 expression in the tissues and then its correlation with the clinicopathological parameters and prognosis of EOC was analyzed. ResultsRBMS3 was expressed in both EOC and benign epithelial ovarian tumor tissues. RBMS3 expression in EOC tissues， significantly related with International Federation of Gynecology and Obstetrics （FIGO） stage， histological grade， CEA levels and survival status， was significantly lower than that in benign epithelial ovarian tumor tissues （P<0.05）. Kaplan–Meier survival curve showed that low RBMS3 expression in EOC patients was correlated with decreased progression-free survival （PFS） and overall survival （OS） （P<0.05）. Univariate analysis showed that RBMS3 expression， FIGO stage， residual lesion size， intestinal metastasis and intraperitoneal implantation were associated with OS of EOC patients （P<0.05）； multivariate analysis showed that low RBMS3 expression and intestinal metastasis were independent risk factors for poor prognosis in EOC patients （P<0.05）. ConclusionsRBMS3 is expressed at low levels in EOC tissues， which is closely related to poor prognosis of EOC patients. RBMS3 may function as a tumor suppressor gene in EOC tissues and can be used as an EOC-independent prognostic marker for targeted therapy against EOC.

Hepatoprotective activity of cis-(trans)-emodin-emodin dianthrone from Polygonum multiflorum Thunb / 药学学报

The cis-emodin-emodin dianthrone (compound 1) and trans-emodin-emodin dianthrone (compound 2) were extracted from Polygonum multiflorum Thunb. The protective effect and mechanism of compound 1 and compound 2 (emodin-emodin dianthrones) on acute liver injury induced by concanavalin A (ConA) in ICR mice was first investigated. The results indicated that emodin-emodin dianthrones at 1 mg·kg-1 significantly reduced serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) level (P < 0.05). Emodin-emodin dianthrones also improved liver histopathological damage in liver-injured mice. The level of Bcl-2-associated X protein (Bax) mRNA in liver was significantly reduced by 1 mg·kg-1 of emodin-emodin dianthrones, while the level of B-cell lymphoma-2 (Bcl-2) mRNA expression was significantly increased (P < 0.05). The protective activity of compounds 1 and 2 against hepatocyte injury was further evaluated by hydrogen peroxide (H2O2)-induced hepatocyte injury. Compounds 1 and 2 significantly inhibited H2O2-induced hepatocyte injury and reduced the levels of ALT, AST, alkaline phosphatase (ALP), and lactate dehydrogenase (LDH) in cell culture. Compounds 1 and 2 also significantly improved the cell survival rate and decreased H2O2-induced oxidative stress in hepatocytes. Compound 1 (0.5 µmol·L-1) significantly increased the enzymatic activity of superoxide dismutase (SOD) in hepatocytes (P < 0.01), and 0.5 µmol·L-1 of compound 2 significantly decreased the intracellular reactive oxygen species (ROS), increased SOD enzyme activity, and glutathione (GSH) content (P < 0.01). Compounds 1 and 2 at 0.5 µmol·L-1 also inhibited hepatocyte apoptosis by increasing the protein expression ratio of Bcl-2/Bax (P < 0.05) and decreasing the protein expression ratio of cleaved caspase-3 and pro caspase-3 (P < 0.05). This study indicates that the emodin-emodin dianthrones from Polygonum multiflorum Thunb. have liver-protective activity. Compounds 1 and 2 exerted hepatoprotective effects by inhibiting apoptosis and oxidative stress. The study provides an important material basis for the hepatoprotective effect of commonly used amounts of Polygonum multiflorum Thunb.

Research progress of anti-acute marrow leukemia drugs by targeting FLT3 / 药学学报

Acute myeloid leukemia (AML) is a genetic heterogeneous disease in which primordial and juvenile myeloid cells proliferate or accumulate abnormally in bone marrow, peripheral blood and other tissues, resulting in damage to normal hematopoietic function. Studies have shown that about 30% of AML patients have FMS-like tyrosine kinase 3 (FLT3), FLT3 abnormal regulation is closely related to the occurrence and development of AML. At present, FLT3 has become an important target for developing small molecular targeted drugs. Currently, a variety of FLT3 inhibitors and FLT3 degraders have been developed targeting FLT3, and some compounds have exhibited good anti-AML activity. This article summarizes and sorts out the current mainstream drugs for AML therapeutic targeting FLT3, in order to provide a reference for the development and design of AML drugs.

Efficacy of perioperative use of tigecycline in preventing infection and incidence of hypofibrinogenemia in liver transplant recipients / 器官移植

Objective To evaluate the efficacy of perioperative use of tigecycline in preventing infection and the incidence of hypofibrinogenemia in liver transplant recipients. Methods Clinical data of 40 liver transplant recipients given with tigecycline to prevent infection were retrospectively analyzed. The incidence of infection in recipients and donor-derived infection were analyzed. The changes of clinical indexes in recipients during, upon the completion and (7±2) d after tigecycline treatment were analyzed, respectively. The incidence and treatment of hypofibrinogenemia were summarized. Results Among 40 liver transplant recipients, 2 cases were infected by aspergillus niger and cytomegalovirus, out of the antibacterial spectrum of tigecycline. After adjusting the anti-infection regimen, the infection was properly controlled. Liver allografts were positive for relevant culture in 9 cases, whereas none of them progressed into donor-derived infection. Approximately at postoperative 2 weeks, all 40 recipients restored liver function and were discharged from hospital. Among them, 6 recipients developed hypofibrinogenemia complicated with coagulation disorder at postoperative 2-4 d, whereas transaminase level, bilirubin level and infection-related indexes were gradually decreased after liver transplantation, and albumin level was stable. After supplemented with human fibrinogen and prothrombin complex, coagulation function was improved, but fibrinogen level persistently declined. After terminating use of tigecycline, fibrinogen level was gradually restored to normal range, which might be an adverse drug reaction induced by tigecycline. Conclusions Perioperative anti-infection regimen including tigecycline may reduce the incidence of infection caused by sensitive bacteria in liver transplant recipients. Nevertheless, the incidence of hypofibrinogenemia should be intimately monitored throughout the use of tigecycline.

Influencing factors of survival and prognosis of patients with bladder urothelial carcinoma after surgical treatment and recommendation of an artificial intelligence algorithm / 现代泌尿外科杂志

【Objective】 To explore the factors influencing the survival and prognosis of patients with bladder urothelial carcinoma (BUC) after surgical treatment, and to establish an artificial intelligence algorithm to predict the effects of different surgical regimens. 【Methods】 BUC patients treated with surgery during Jan.2007 and Jan.2019 in The Second Hospital of Dalian Medical University and Nanfang Hospital of Southern Medical University were enrolled. The complete clinical and follow-up data were collected. Deep neural network (DNN) was used to establish an artificial intelligence algorithm model. A prediction model of survival and prognosis was established, and the influencing factors of survival were explored and ranked by the artificial intelligence algorithm. 【Results】 A total of 832 patients were involved, including 438 (52.64%) treated in The Second Hospital of Dalian Medical University, and 394 (47.36%) treated in Nanfang Hospital of Southern Medical University. Of all cases, 579 (69.6%) were non-muscle invasive bladder cancer, and 253 (30.4%) were muscle invasive bladder cancer. Transurethral resection of bladder tumor was conducted in 539 (64.8%) cases, partial cystectomy in 66 (7.9%) cases, and total cystectomy in 227 (27.3%) cases. The data of patients treated in Second Hospital of Dalian Medical University were used for DNN modeling, and the data of patients treated in Nanfang Hospital of Southern Medical University were used for external verification after modeling. Finally, it was concluded that the factors affecting survival and prognosis were T stage, pathological grade, hypertension or cardiovascular and cerebrovascular disease, hemoglobin, blood calcium, smoking, albumin, lymphocytes, age, ratio of albumin/globulin, operation method, N stage, and creatinine clearance rate in descending order. The model could be used for preoperative prediction. 【Conclusion】 Through DNN modeling and external verification, the influencing factors of postoperative survival can be predicted for patients with bladder cancer, and the surgical effects can also be predicted before operation. The model can provide artificial intelligence algorithm support for the selection of surgical methods and postoperative follow-up plans.

Factors affecting penile appearance and erectile function for postoperative hypospadias patients in adulthood: a long-term follow-up observational study / 现代泌尿外科杂志

【Objective】 To investigate the penile appearance, sexual function, psychological status and related influencing factors of adult patients who underwent hypospadias repair surgery in their minors, so as to provide reference for the diagnosis, treatment and prognosis of hypospadias. 【Methods】 This study included 50 adult hypospadias patients who underwent urethroplasty in our hospital during May 2005 and Aug. 2018. The present appearance, sexual function and psychological status were evaluated. The correlation and consistency between hypospadias objective scoring evaluation (HOSE) and pediatric penile perception score (PPPS) were analyzed. Factors affecting the results were determined with univariate and multivariate regression analysis. 【Results】 The satisfaction rate of HOSE was significantly correlated with the urethral length and complications (P=0.024, P=0.033). The satisfaction rate of PPPS was significantly correlated with the number of urethral operations and postoperative complications (P=0.041, P=0.023). There was a weak correlation between HOSE and PPPS (r=0.291, P=0.040), but almost no consistency (Kappa=0.2, P=0.107). Sixty percent of the patients paid attention to the ventral appearance of penis, whose dissatisfaction rate of PPPS was higher than those who did not pay attention to the ventral appearance of the penis (19/30 vs. 6/20, P=0.021). Patients with multiple operations (>1), postoperative complications or unsatisfactory penile appearance were more likely to have inferiority complex (52.6% vs. 22.6%, P=0.029; 59.1% vs.14.3%, P=0.001;61.5% vs. 24.3%, P=0.015). Multivariate regression analysis showed that dissatisfaction with the appearance of the penis was an independent risk factor for patients’ perception of their own physical defects. Among the patients who believed that they had physical defects, the percentage of patients with grade IV penile erectile hardness was significantly lower than that of those who denied they had physical defects (9/17 vs. 27/33, P=0.047). 【Conclusion】 The undesirable postoperative penis appearance is likely to have a negative impact on patients’ long-term psychological state, which might further damage the sexual function in adulthood. Surgeons should pay attention to the penile appearance during the conduction of hypospadias repair.

5 Cases Analysis of Pachydermoperiostosis Complicated with Synovitis / 罕见病研究

  Objective  To analyze the clinical characteristics, treatments and prognosis of pachydermoperiostosis (PDP) with synovitis, and to improve clinicians′ understanding of PDP.  Methods  The clinical data of 5 patients diagnosed with PDP in Peking Union Medical College Hospital from January 2010 to June 2015 were retrospectively analyzed.  Results  Among the 5 patients in this study, all were male, with an average age of (24.2±3.8)years old. The main manifestations of PDP were joint swelling and pain and skin thickening. In this study, all 5 patients were treated with medication, including non-steroidal anti-inflammatory drugs, glucocorticoids, and immunosuppressants, and 4 patients were treated with arthroscopic minimally invasive synovectomy. Their symptoms gradually improved and controlled. The last patient′s symptoms of synovitis were mild and significantly relieved after conservative treatment.  Conclusions  The diagnosis of PDP is still challenging. Symptoms can be alleviated, and the progression of the disease can be basically controlled after active drug therapy and surgical mitigation measures.

HBV laboratory tests and demographic characteristics in 169 897 first-time blood donors / 中国输血杂志

【Objective】 To investigate the HBV infection markers detection and demographic characteristics of first-time blood donors, so as to provide evidence for blood donor recruitment. 【Methods】 HBsAg was detected by ELISA, HBsAg negative samples were tested for HBV DNA, and chemiluminescence method was used to detect HBsAg, HBsAb, HBcAb, HBeAg and HBeAb in first-time blood donor HBsAg-/HBV DNA+ samples. Demographic information of HBsAg positive first-time donors was analyzed. 【Results】 From 2018 to 2022, a total of 502 739 people participated in voluntary blood donation, and first-time blood donors accounted for 33.79%. The HBsAg positive rate of first-time donors(28.37/10 000, 482/169 897)was higher than that of repeated blood donors(3.46/10 000, 115/332 842) (OR=8.23, 95%CI: 6.72~10.09), and the HBV DNA positive rate of first-time blood donors(4.83/10 000, 82/169 897)was lower than that of repeated blood donors(6.52/10 000, 217/332 842)(OR=0.74, 95%CI: 0.57~0.95). The positive rate of HBcAb in HBsAg-/HBV DNA+ samples of first-time blood donors was 73.17%. Significant differences were noticed in HBsAg-/HBV DNA+ and HBsAg positive rate among first-time blood donors among gender, age, education background and occupation (all P<0.05). 【Conclusion】 Low risk first-time blood donor recruitment is important for blood donation. Strengthening HBV screening before blood donation and detection after blood donation is beneficial to improve the safety of blood transfusion.

Global progress in peptide radiopharmaceutical research and China's opportunities / 药学学报

Radiopharmaceutical is an essential component of nuclear medicine and molecular imaging, as well as a key component of precision medicine. The United States Food and Drug Administration (FDA) has recently approved the marketing of several peptide-based radiopharmaceuticals, sparking a global trend of research in this area and propelling nuclear medicine into the precision theranostic era. This has created a new wave of technological competition in the field of nuclear medicine. It is the responsibility of Chinese scientists in the radiopharmaceutical field to capitalize on this opportunity, leverage the momentum, and strengthen their independent innovation capability in order to stay ahead in the future global nuclear science and technology competition. This review provides an overview of the remarkable progress made in the research, development, and translation of global peptide-based radiopharmaceuticals. It examines the advantages of peptide-based radiopharmaceuticals and outlines the current hot targets and progress in drug development in this field. Additionally, it proposes six opportunities for China to overtake others in the field of peptide-based radiopharmaceuticals and achieve technological self-reliance, based on interdisciplinary collaboration and independent innovation. Lastly, the future prospect of peptide-based radiopharmaceuticals is discussed.

Research status of Bovis Calculus and relevant Chinese patent medicines based on bibliometric analysis / 中国中药杂志

With scarce resources, natural Bovis Calculus is expensive and hard to meet clinical demand. At the moment, four kinds of Bovis Calculus are available on the market: the natural product, in vitro cultured product, synthesized product, and the product formed in cow after manual intervention. In this study, papers on the four kinds of Bovis Calculus products and relevant Chinese patent medicines were searched from Web of Science, PubMed, and China National Knowledge Infrastructure(CNKI). CiteSpace, citexs AI, and CNKI were employed for bibliometric analysis and knowledge map analysis. On this basis, the status, trend, and focuses of research on Bovis Calculus and relevant Chinese patent medicines were summarized. The results suggested overall slow development in the research on Bovis Calculus and relevant Chinese patent medicines with three typical growth stages. It is consistent with the development of Bovis Calculus substitutes and the national policy for the development of traditional Chinese medicine. At the moment, the research on Bovis Calculus and relevant Chinese patent medicines has been on the rise. In recent years, there has been an explosion of research on them, particularly the quality control of Bovis Calculus and the Chinese patent medicines, the pharmacological efficacy of Chinese patent medicines, such as Angong Niuhuang Pills, and the comparison of the quality of various Bovis Calculus products. However, there is a paucity of research on the pharmacological efficacy and the mechanism of Bovis Calculus. This medicinal and the relevant Chinese patent medicines have been studied from diverse perspectives and China becomes outstanding in this research field. However, it is still necessary to reveal the chemical composition, pharmacological efficacy, and mechanism through multi-dimensional deep research.

Role of NLRP3 Inflammasome in Bone and Joint Diseases and Traditional Chinese Medicine Intervention： A Review / 中国实验方剂学杂志

Nucleotide binding oligomeric dome-like receptor protein 3 （NLRP3） inflammasome is an intracellular sensing protein complex， and it is an important player in the innate immune system， capable of sensing foreign pathogens and endogenous danger signals. After tissue injury， the activation of the NLRP3 inflammasome induces the release of the pro-inflammatory cytokines interleukin （IL）-1β and IL-18， while promoting gasdermin D-mediated pyroptosis. Existing studies have shown that NLRP3 inflammasome plays a key role in the occurrence and development of common bone and joint diseases such as osteoporosis， osteoarthritis， rheumatoid arthritis， and gouty arthritis by inducing inflammatory cascade reaction and accelerating bone resorption and cartilage destruction. Therefore， blocking the NLRP3 inflammasome signaling pathway may be an effective strategy to treat or prevent bone and joint diseases. Currently， researchers have developed and tested several drugs that selectively target the NLRP3 inflammasome in animal and clinical studies， but the progress has been poor due to obvious side effects and high prices. Traditional Chinese medicine （TCM） has been widely recognized in the treatment of bone and joint diseases due to its unique advantages of multi-target， multi-pathway， multi-mechanism synergism， low price， and low side effects. With the deepening of research， the targeted intervention of NLRP3 inflammasome by TCM in the treatment of bone and joint diseases has attracted wide attention. In this paper， the mechanism of NLRP3 inflammasome in osteoarthritis was summarized by analyzing relevant literature in China and abroad in recent years， and the progress of targeted intervention of NLRP3 inflammasome by TCM in the treatment of bone and joint diseases was systematically reviewed， so as to provide new ideas and theoretical basis for the treatment of bone and joint diseases.

Similarities and differences of myocardial metabolic characteristics between HFpEF and HFrEF mice based on LC-MS/MS metabolomics / 中华心血管病杂志

Objective: To reveal the similarities and differences in myocardial metabolic characteristics between heart failure with preserved ejection fraction (HFpEF) and heart failure with reduced ejection fraction (HFrEF) mice using metabolomics. Methods: The experimental mice were divided into 4 groups, including control, HFpEF, sham and HFrEF groups (10 mice in each group). High fat diet and Nω-nitroarginine methyl ester hydrochloride (L-NAME) were applied to construct a"two-hit"HFpEF mouse model. Transverse aortic constriction (TAC) surgery was used to construct the HFrEF mouse model. The differential expression of metabolites in the myocardium of HFpEF and HFrEF mice was detected by untargeted metabolomics (UHPLC-QE-MS). Variable importance in projection>1 and P<0.05 were used as criteria to screen and classify the differentially expressed metabolites between the mice models. KEGG functional enrichment and pathway impact analysis demonstrated significantly altered metabolic pathways in both HFpEF and HFrEF mice. Results: One hundred and nine differentially expressed metabolites were detected in HFpEF mice, and 270 differentially expressed metabolites were detected in HFrEF mice. Compared with the control group, the most significantly changed metabolite in HFpEF mice was glycerophospholipids, while HFrEF mice presented with the largest proportion of carboxylic acids and their derivatives. KEGG enrichment and pathway impact analysis showed that the differentially expressed metabolites in HFpEF mice were mainly enriched in pathways such as biosynthesis of unsaturated fatty acids, ether lipid metabolism, amino sugar and nucleotide sugar metabolism, glycerophospholipid metabolism, arachidonic acid metabolism and arginine and proline metabolism. The differentially expressed metabolites in HFrEF mice were mainly enriched in arginine and proline metabolism, glycine, serine and threonine metabolism, pantothenate and CoA biosynthesis, glycerophospholipid metabolism, nicotinate and nicotinamide metabolism and arachidonic acid metabolism, etc. Conclusions: HFpEF mice have a significantly different myocardial metabolite expression profile compared with HFrEF mice. In addition, biosynthesis of unsaturated fatty acids, arachidonic acid metabolism, glycerophospholipid metabolism and arginine and proline metabolism are significantly altered in both HFpEF and HFrEF mice, suggesting that these metabolic pathways may play an important role in disease progression in both types of heart failure.

Outcome of surgical repair for aortic coarctation with coexisting descending aortic aneurysm in adult patients / 中华心血管病杂志

Objective: To evaluate the efficacy of surgical treatment of aortic coarctation combined with descending aortic aneurysm in adult patients. Methods: This is a retrospective cohort study. Adult patients with aortic coarctation who were hospitalized in Beijing Anzhen Hospital from January 2015 to April 2019 were enrolled. The aortic coarctation was diagnosed by aortic CT angiography, and the included patients were divided into the combined descending aortic aneurysm group and the uncomplicated descending aortic aneurysm group based on descending aortic diameter. General clinical data and surgery-related data were collected from the included patients, and death and complications were recorded at 30 days after surgery, and upper limb systolic blood pressure was measured in all patients at discharge. Patients were followed up after discharge by outpatient visit or telephone call for their survival and the occurrence of repeat interventions and adverse events, which included death, cerebrovascular events, transient ischemic attack, myocardial infarction, hypertension, postoperative restenosis, and other cardiovascular-related interventions. Results: A total of 107 patients with aortic coarctation aged (34.1±15.2) years were included, and 68 (63.6%) were males. There were 16 cases in the combined descending aortic aneurysm group and 91 cases in the uncomplicated descending aortic aneurysm group. In the combined descending aortic aneurysm group, 6 cases (6/16) underwent artificial vessel bypass, 4 cases (4/16) underwent thoracic aortic artificial vessel replacement, 4 cases (4/16) underwent aortic arch replacement+elephant trunk procedure, and 2 cases (2/16) underwent thoracic endovascular aneurysm repair. There was no statistically significant difference between the two groups in the choice of surgical approach (all P>0.05). In the combined descending aortic aneurysm group at 30 days after surgery, one case underwent re-thoracotomy surgery, one case developed incomplete paraplegia of the lower extremity, and one case died; and the differences in the incidence of endpoint events at 30 days after surgery were similar between the two groups (P>0.05). Systolic blood pressure in the upper extremity at discharge was significantly lower in both groups compared with the preoperative period (in the combined descending aortic aneurysm group: (127.3±16.3) mmHg vs. (140.9±16.3) mmHg, P=0.030, 1 mmHg=0.133 kPa; in the uncomplicated descending aortic aneurysm group: (120.7±13.2) mmHg vs. (151.8±26.3) mmHg, P=0.001). The follow-up time was 3.5 (3.1, 4.4) years. There were no new deaths in the combined descending aortic aneurysm group, no transient ischemic attack, myocardial infarction or re-thoracotomy surgery, and one patient (1/15) suffered cerebral infarction and 10 patients (10/15) were diagnosed with hypertension. The differences in the occurrence of endpoint events during postoperative follow-up were similar between the two groups (P>0.05). Conclusion: In experienced centers, long-term prognosis of patients with aortic coarctation combined with descending aortic aneurysm is satisfactory post surgical intervention.

The effect of PLK1 inhibitor in osimertinib resistant non-small cell lung carcinoma cells / 浙江大学学报·医学版

OBJECTIVES@#To investigate the effects of PLK1 inhibitors on osimertinib-resistant non-small cell lung carcinoma (NSCLC) cells and the anti-tumor effect combined with osimertinib.@*METHODS@#An osimertinib resistant NCI-H1975 cell line was induced by exposure to gradually increasing drug concentrations. Osimertinib-resistant cells were co-treated with compounds from classical tumor pathway inhibitor library and osimertinib to screen for compounds with synergistic effects with osimertinib. The Gene Set Enrichment Analysis (GSEA) was used to investigate the activated signaling pathways in osimertinib-resistant cells; sulforhodamine B (SRB) staining was used to investigate the effect of PLK1 inhibitors on osimertinib-resistant cells and the synergistic effect of PLK1 inhibitors combined with osimertinib.@*RESULTS@#Osimertinib-resistance in NCI-H1975 cell (resistance index=43.45) was successfully established. The PLK1 inhibitors GSK 461364 and BI 2536 had synergistic effect with osimertinib. Compared with osimertinib-sensitive cells, PLK1 regulatory pathway and cell cycle pathway were significantly activated in osimertinib-resistant cells. In NSCLC patients with epidermal growth factor receptor mutations treated with osimertinib, PLK1 mRNA levels were negatively correlated with progression free survival of patients (R=－0.62, P<0.05), indicating that excessive activation of PLK1 in NSCLC cells may cause cell resistant to osimertinib. Further in vitro experiments showed that IC50 of PLK1 inhibitors BI 6727 and GSK 461364 in osimertinib-resistant cells were lower than those in sensitive ones. Compared with the mono treatment of osimertinib, PLK1 inhibitors combined with osimertinib behaved significantly stronger effect on the proliferation of osimertinib-resistant cells.@*CONCLUSIONS@#PLK1 inhibitors have a synergistic effect with osimertinib on osimertinib-resistant NSCLC cells which indicates that they may have potential clinical value in the treatment of NSCLC patients with osimertinib resistance.

Deubiquitinating enzyme JOSD2 affects susceptibility of non-small cell lung carcinoma cells to anti-cancer drugs through DNA damage repair / 浙江大学学报·医学版

OBJECTIVES@#To investigate the effects and mechanisms of deubiquitinating enzyme Josephin domain containing 2 (JOSD2) on susceptibility of non-small cell lung carcinoma (NSCLC) cells to anti-cancer drugs.@*METHODS@#The transcriptome expression and clinical data of NSCLC were downloaded from the Gene Expression Omnibus. Principal component analysis and limma analysis were used to investigate the deubiquitinating enzymes up-regulated in NSCLC tissues. Kaplan-Meier analysis was used to investigate the relationship between the expression of deubiquitinating enzymes and overall survival of NSCLC patients. Gene ontology enrichment and gene set enrichment analysis (GSEA) were used to analyze the activation of signaling pathways in NSCLC patients with high expression of JOSD2. Gene set variation analysis and Pearson correlation were used to investigate the correlation between JOSD2 expression levels and DNA damage response (DDR) pathway. Western blotting was performed to examine the expression levels of JOSD2 and proteins associated with the DDR pathway. Immunofluorescence was used to detect the localization of JOSD2. Sulforhodamine B staining was used to examine the sensitivity of JOSD2-knock-down NSCLC cells to DNA damaging drugs.@*RESULTS@#Compared with adjacent tissues, the expression level of JOSD2 was significantly up-regulated in NSCLC tissues (P<0.05), and was significantly correlated with the prognosis in NSCLC patients (P<0.05). Compared with the tissues with low expression of JOSD2, the DDR-related pathways were significantly upregulated in NSCLC tissues with high expression of JOSD2 (all P<0.05). In addition, the expression of JOSD2 was positively correlated with the activation of DDR-related pathways (all P<0.01). Compared with the control group, overexpression of JOSD2 significantly promoted the DDR in NSCLC cells. In addition, DNA damaging agents significantly increase the nuclear localization of JOSD2, whereas depletion of JOSD2 significantly enhanced the sensitivity of NSCLC cells to DNA damaging agents (all P<0.05).@*CONCLUSIONS@#Deubiquitinating enzyme JOSD2 may regulate the malignant progression of NSCLC by promoting DNA damage repair pathway, and depletion of JOSD2 significantly enhances the sensitivity of NSCLC cells to DNA damaging agents.

Research and development practice of traditional Chinese medicine based on network target theory and technology / 中国中药杂志

Network targets theory and technology have transcended the limitations of the "single gene, single target" model, aiming to decipher the mechanisms of traditional Chinese medicine(TCM) based on biological network from the perspective of informatics and system. As the core of TCM network pharmacology, with the development of computer science and high-throughput experimental techniques, the network target theory and technology are beginning to exhibit a trend of organic integration with artificial intelligence technology and high-throughput multi-modal multi-omics experimental techniques. Taking the network target analysis of TCM like Yinqiao Qingre Tablets as a typical case, network target theory and technology have achieved the systematic construction, in-depth analysis, and high-throughput multi-modal multi-omics validation of multi-level biological networks spanning from traditional Chinese and Western phenotypes to tissues, cells, molecules, and traditional Chinese and Western medicines. This development helps to address critical issues in the analysis of mechanisms of TCM, including the discovery of key targets, identification of functional components, discovery of synergistic effects among compound ingredients, and elucidation of the regulatory mechanisms of formulae. It provides powerful theoretical and technological support for advancing clinical precision diagnosis and treatment, precise positioning of TCM, and precise research and development of TCM. Thus, a new paradigm of TCM research gradually emerges, combining big data and artificial intelligence(AI) with the integration of human experience and scientific evidence.