Comparison of Anatomically of Medial Plantar Flap versus Reverse Sural Fasciocutaneous Flap in the Treatment of Skin Defects After Cutaneous Squamous Cell Carcinoma Excision

SUMMARY: To compare the advantages and disadvantages of reverse sural fasciocutaneous flap (RSFF) versus medial plantar flap (MPF) in the treatment of skin defects after excision of squamous cell carcinoma (SCC) of the heel. The research participants were 80 SCC patients admitted to Lishui People's Hospital between January 2019 and April 2022, who were assigned to RSFF group (n=37) and MPF group (n=43) according to the flap type. After a one-year follow-up, the survival, flap necrosis and ulceration, as well as pain and tactile sensation recovery of both groups were counted. At the last follow-up, the clinical response was evaluated, and Short-Form 36 Item Health Survey (SF-36) and appearance satisfaction surveys were conducted. No patients died in either group, and one patient in each group developed flap necrosis. The MPF group had better sensory recovery and a lower incidence of flap ulceration (P0.05). The cosmetic satisfaction was higher in MPF group than in RSFF group (P<0.05). MPF contributes to beautiful appearance, better sensory recovery, and low risk of long-term ulceration, while RSFF is suitable for lesions with large defects or those located at the lateral heel.

El objetivo del estudio fue comparar las ventajas y desventajas del colgajo fasciocutáneo sural inverso (RSFF) versus el colgajo plantar medial (MPF) en el tratamiento de defectos de la piel después de la escisión de un carcinoma de células escamosas (CCE) del talón. Los participantes de la investigación fueron 80 pacientes con CCE ingresados en el Hospital Popular de Lishui entre enero de 2019 y abril de 2022, que fueron asignados al grupo RSFF (n=37) y al grupo MPF (n=43) según el tipo de colgajo. Después de un año de seguimiento, se observó la supervivencia, la necrosis y ulceración del colgajo, así como la recuperación del dolor y la sensación táctil de ambos grupos. En el último seguimiento, se evaluó la respuesta clínica y se realizaron encuestas de salud de formato corto de 36 ítems (SF-36) y encuestas de satisfacción. Ningún paciente falleció en ninguno de los grupos y un paciente de cada grupo desarrolló necrosis del colgajo. El grupo MPF tuvo una mejor recuperación sensorial y una menor incidencia de ulceración del colgajo (P 0,05). La satisfacción cosmética fue mayor en el grupo MPF que en el grupo RSFF (P<0,05). MPF contribuye a una mejor apariencia, mejor recuperación sensorial y un bajo riesgo de ulceración a largo plazo, mientras que RSFF es adecuado para lesiones con defectos grandes o localizados en la parte lateral del talón.

Identify risk factors for perioperative outcomes in Intracorporeal Urinary Diversion and Extracorporeal Urinary Diversion with Robotic Cystectomy

ABSTRACT Introduction: The increasing adoption of robotic-assisted cystectomy with intracorporeal urinary diversion (ICUD), despite its complexity, prompts a detailed comparison with extracorporeal urinary diversion (ECUD). Our study at a single institution investigates perioperative outcomes and identifies risk factors impacting the success of these surgical approaches. Methods: In this retrospective analysis, 174 patients who underwent robotic-assisted cystectomy at the University of Louisville from June 2016 to August 2021 were reviewed. The cohort was divided into two groups based on the urinary diversion method: 30 patients underwent ECUD and 144 underwent ICUD. Data on demographics, complication rates, length of hospital stay, and readmission rates were meticulously collected and analyzed. Results: Operative times were comparable between the ICUD and ECUD groups. However, the ICUD group had a significantly lower intraoperative transfusion rate (0.5 vs. 1.0, p=0.02) and shorter hospital stay (7.8 vs. 12.3 days, p<0.001). Factors such as male sex, smoking history, diabetes mellitus, intravesical therapy, higher ASA, and ACCI scores were associated with increased Clavien-Dindo Grade 3 or higher complications. Age over 70 was the sole factor linked to a higher 90-day readmission rate, with no specific characteristics influencing the 30-day rate. Conclusion: Robotic cystectomy with ICUD results in shorter hospitalizations and lower intraoperative transfusion rates compared to ECUD, without differences in operative time, high-grade postoperative complications, or readmission rates. These findings can inform clinical decision-making, highlighting ICUD as a potentially more favorable option in appropriate settings.

Silencing of matrix metalloprotease-12 delays the progression of castration-resistant prostate cancer by regulating autophagy and lipolysis

Abstract The complex pathogenesis of castration-resistant prostate cancer (CRPC) makes it challenging to identify effective treatment methods. Matrix metalloproteinase (MMP)-12 can degrade elastin as well as various extracellular matrix (ECM) components, which is associated with cancer progression. However, the relationship between MMP-12 and CRPC progression is poorly understood. In this study, we observed the effect of MMP-12 on the progression of CRPC and further explored its potential mechanism of action. High levels of MMP-12 were observed in patients with CRPC. We therefore developed cell co-culture and mouse models to study the function of MMP-12. Silencing MMP-12 in CRPC cells disrupted lipid utilization and autophagy marker expression via the CD36/CPT1 and P62/LC3 pathways, respectively, leading to reduced CRPC cell migration and invasion. Moreover, animal experiments confirmed that MMP-12-knockdown CRPC xenograft tumors exhibited reduced tumor growth, and the mechanisms involved the promotion of cancer cell autophagy and the inhibition of lipid catabolism. According to our results, MMP-12 played important roles in the progression of CRPC by disrupting adipocyte maturation and regulating cancer migration and invasion via the modulation of autophagy and lipid catabolism pathways.

Overexpression SPRY2 Suppresses Esophageal Squamous Cell Carcinoma Progression Via Inactivation of ERK/AKT Signaling / La Sobreexpresión SPRY2 Suprime la Evolución del Carcinoma de Células Escamosas de Esófago Mediante la Inactivación de la Señalización ERK/AKT

SUMMARY: Esophageal cancer is one of the most aggressive gastrointestinal cancers. Invasion and metastasis are the main causes of poor prognosis of esophageal cancer. SPRY2 has been reported to exert promoting effects in human cancers, which controls signal pathways including PI3K/AKT and MAPKs. However, the expression of SPRY2 in esophageal squamous cell carcinoma (ESCC) and its underlying mechanism remain unclear. In the present study, we aimed to investigate the detailed role of SPRY2 in the regulation of cell proliferation, invasion and ERK/AKT signaling pathway in ESCC. It was identified that the expression level of SPRY2 in ESCC was remarkably decreased compared with normal tissues, and it was related to clinicopathologic features and prognosis ESCC patients. The upregulation of SPRY2 expression notably inhibited the proliferation, migration and invasion of Eca-109 cells. In addition, the activity of ERK /AKT signaling was also suppressed by the SPRY2 upregulation in Eca-109 cells. Our study suggests that overexpression of SPRY2 suppress cancer cell proliferation and invasion of by through suppression of the ERK/AKT signaling pathways in ESCC. Therefore, SPRY2 may be a promising prognostic marker and therapeutic target for ESCC.

El cáncer de esófago es uno de los cánceres gastrointestinales más agresivos. La invasión y la metástasis son las principales causas de mal pronóstico del cáncer de esófago. Se ha informado que SPRY2 ejerce efectos promotores en los cánceres humanos, que controla las vías de señales, incluidas PI3K/AKT y MAPK. Sin embargo, la expresión de SPRY2 en el carcinoma de células escamosas de esófago (ESCC) y su mecanismo subyacente aún no están claros. En el presente estudio, nuestro objetivo fue investigar el papel detallado de SPRY2 en la regulación de la proliferación celular, la invasión y la vía de señalización ERK/AKT en ESCC. Se identificó que el nivel de expresión de SPRY2 en ESCC estaba notablemente disminuido en comparación con los tejidos normales, y estaba relacionado con las características clínico-patológicas y el pronóstico de los pacientes con ESCC. La regulación positiva de la expresión de SPRY2 inhibió notablemente la proliferación, migración e invasión de células Eca-109. Además, la actividad de la señalización de ERK/AKT también fue suprimida por la regulación positiva de SPRY2 en las células Eca-109. Nuestro estudio sugiere que la sobreexpresión de SPRY2 suprime la proliferación y la invasión de células cancerosas mediante la supresión de las vías de señalización ERK/AKT en ESCC. Por lo tanto, SPRY2 puede ser un marcador de pronóstico prometedor y un objetivo terapéutico para la ESCC.

Prevalence and risk factors for falls among older Chinese adults in the community: findings from the CLHLS study

Older adults have a high prevalence of falls due to a decline in physiological functions and various chronic diseases. This study aimed to investigate the prevalence of and risk factors for falls among older individuals in the Chinese Longitudinal Healthy Longevity Survey (CLHLS). We collected information from 9737 older individuals (average age=84.26 years) from the CLHLS and used binary logistic regression analysis to explore the independent risk factors and protective factors for falls. The logistic regression analysis results are reported as adjusted odds ratios (aORs) and 95% confidence intervals (95%CIs). The prevalence of falls among older adults in China was 21.6%, with women (24.6%) having a higher prevalence than men (18.1%). Logistic regression analysis revealed that never (or rarely) eating fresh fruit, difficulty with hearing, cataracts, and arthritis were the common independent risk factors for falls in older Chinese men and women. Among men, age ≥80 years (aOR=1.86), never doing housework (aOR=1.36), and dyslipidemia (aOR=1.47) were risk factors, while eating milk products once a week was a protective factor. Alcohol consumption (aOR=1.40), physical labor (aOR=1.28), and heart disease (aOR=1.21) were risk factors for falls in women, while a daily sleep duration of 6-12 h and garlic consumption once a week were protective factors. The prevalence of falls among older adults in China is 21.6% and is greater in women than in men. These risk and protective factors can be used to formulate reasonable recommendations for living habits, diet, and chronic disease control strategies.

Integrative analyses of genetic characteristics associated with skeletal endothelial cells

Abstract The osseous vascular endothelium encompasses a vast intricate framework that regulates bone remodeling. Osteoporosis, an age-associated systemic bone disease, is characterized by the degeneration of the vascular architecture. Nevertheless, the precise mechanisms underpinning the metamorphosis of endothelial cells (ECs) with advancing age remain predominantly enigmatic. In this study, we conducted a systematic analysis of differentially expressed genes (DEGs) and the associated pathways in juvenile and mature femoral ECs, utilizing data sourced from the Gene Expression Omnibus (GEO) repositories (GSE148804) and employing bioinformatics tools. Through this approach, we successfully discerned six pivotal genes, namely Adamts1, Adamts2, Adamts4, Adamts14, Col5a1, and Col5a2. Subsequently, we constructed a miRNA-mRNA network based on miRNAs displaying differential expression between CD31hiEMCNhi and CD31lowEMCNlow ECs, utilizing online repositories for prediction. The expression of miR-466i-3p and miR-466i-5p in bone marrow ECs exhibited an inverse correlation with age. Our in vivo experiments additionally unveiled miR-466i-5p as a pivotal regulator in osseous ECs and a promising therapeutic target for age-related osteoporosis.

Influence of reminiscence therapy on mental health and quality of life in elderly patients with unresectable, metastatic gastrointestinal cancer

Reminiscence therapy (RT) attenuates psychological disorders in cancer patients. This study aimed to evaluate the effect of RT on anxiety, depression, spiritual well-being, and quality of life in elderly patients with unresectable, metastatic gastrointestinal cancer. A total of 222 elderly patients with unresectable, metastatic gastrointestinal cancer were randomized into RT group (RT plus usual care, n=112) or control group (usual care, n=110) with a 6-month intervention. Hospital Anxiety and Depression Scale for Anxiety (HADS-A) and Depression (HADS-D), Functional Assessment of Chronic Illness Therapy-Spiritual Well-Being Scale (FACIT-Sp), and Quality of Life Questionnaire-Core 30 (QLQ-C30) were evaluated at month (M)0, M1, M3, and M6. Concerning the primary outcome, HADS-A score at M6 decreased in the RT group compared to the control group (P=0.005). As to secondary outcomes, the RT group showed decreased HADS-A scores at M3, anxiety rate at M3, HADS-D scores at M3 and M6, depression rate at M6, as well as greater FACIT-Sp scores at M1, M3, and M6 vs the control group (all P<0.050). Additionally, QLQ-C30 global health score was elevated at M1 (P=0.046) and M6 (P=0.005), functions score was greater at M6 (P=0.038), and symptoms score was lower at M3 (P=0.019) in the RT group than in the control group. Subgroup analysis revealed that the addition of RT was more effective for patients with anxiety or depression at baseline. In summary, RT alleviated anxiety and depression, and improved the spiritual well-being and quality of life within 6 months in elderly patients with unresectable, metastatic gastrointestinal cancer.

Combining metabolomics and network pharmacology to investigate the protective effect of Jiawei Xinglou Chengqi Granules in ischemic stroke

Jiawei Xinglou Chengqi Granule (JXCG) is an effective herbal medicine for the treatment of ischemic stroke (IS). JXCG has been shown to effectively ameliorate cerebral ischemic symptoms in clinical practice, but the underlying mechanisms are unclear. In this study, we investigated the mechanisms of action of JXCG in the treatment of IS by combining metabolomics with network pharmacology. The chemical composition of JXCG was analyzed using ultra-high performance liquid chromatography-high resolution mass spectrometry (UHPLC-HRMS). Ultra-high performance liquid chromatography-tandem time-of-flight mass spectrometry (UHPLC-Q-TOF MS) untargeted metabolomics were used to identify differential metabolites within metabolic pathways. Network pharmacology was applied to mine potential targets of JXCG in the treatment of IS. The identified key targets were validated by constructing an integrated network of metabolomics and network pharmacology and by molecular docking using Cytoscape. The effect of JXCG on IS was evaluated in vivo, and the predicted targets and pathways of JXCG in IS therapy were assessed using immunoblotting. Combining metabolomics and network pharmacology, we identified the therapeutic targets of JXCG for IS. Notably, JXCG lessened neuronal damage and reduced cerebral infarct size in rats with IS. Western blot analysis showed that JXCG upregulated PRKCH and downregulated PRKCE and PRKCQ proteins. Our combined network pharmacology and metabolomics findings showed that JXCG may have therapeutic potential in the treatment of IS by targeting multiple factors and pathways.

Endothelial cell ferroptosis influences IDH wild-type glioblastoma growth in recurrent glioblastoma multiforme patients

Glioblastomas are known for their poor clinical prognosis, with recurrent tumors often exhibiting greater invasiveness and faster growth rates compared to primary tumors. To understand the intratumoral changes driving this phenomenon, we employed single-cell sequencing to analyze the differences between two pairs of primary and recurrent glioblastomas. Our findings revealed an upregulation of ferroptosis in endothelial cells within recurrent tumors, identified by the significant overexpression of the NOX4 gene. Further analysis indicated that knocking down NOX4 in endothelial cells reduced the activity of the ferroptosis pathway. Utilizing conditioned media from endothelial cells with lower ferroptosis activity, we observed a decrease in the growth rate of glioblastoma cells. These results highlighted the complex role of ferroptosis within tumors and suggested that targeting ferroptosis in the treatment of glioblastomas requires careful consideration of its effects on endothelial cells, as it may otherwise produce counterproductive outcomes.

Ag85B with c-di-AMP as mucosal adjuvant showed immunotherapeutic effects on persistent Mycobacterium tuberculosis infection in mice

Tuberculosis (TB), caused by Mycobacterium tuberculosis, remains the leading cause of mortality by a single infectious agent in the world. M. tuberculosis infection could also result in clinical chronic infection, known as latent TB infection (LTBI). Compared to the current limited treatment, several subunit vaccines showed immunotherapeutic effects and were included in clinical trials. In this study, a subunit vaccine of Ag85B with a novel mucosal adjuvant c-di-AMP (Ag85B:c-di-AMP) was delivered intranasally to a persistent M. tuberculosis H37Ra infection mouse model, which also presented the asymptomatic characteristics of LTBI. Compared with Ag85B immunization, Ag85B:c-di-AMP vaccination induced stronger humoral immune responses, significantly higher CD4+ T cells recruitment, enhanced Th1/Th2/Th17 profile response in the lung, decreased pathological lesions of the lung, and reduced M. tuberculosis load in mice. Taken together, Ag85B:c-di-AMP mucosal route immunization provided an immunotherapeutic effect on persistent M. tuberculosis H37Ra infection, and c-di-AMP, as a promising potential mucosal adjuvant, could be further used in therapeutic or prophylactic vaccine strategies for persistent M. tuberculosis infection as well as LTBI.

Regulatory Effect of Modified Banxia Shumi Decoction on Orexin and Its Receptor in Hypothalamus of Insomnia Model Rats / 广州中医药大学学报

Objective To observe the therapeutic effect and mechanism of Modified Banxia Shumi Decoction on p-chlorophenylalanine(PCPA)-induced insomnia model rats.Methods Forty-eight male SD rats were randomly divided into six groups,i.e.,the normal group,the model group,the low-,medium-and high-dose groups of Chinese medicine and the Diazepam group,with 8 rats in each group.For 7 consecutive days before modeling,rats in the Chinese medicine low-,medium-and high-dose groups were treated with Modified Banxia Shumi Decoction for prophylactic treatment.Except for the normal group,PCPA-induced insomnia rat model was established in all groups.After modeling on day 1,each group continued to be administered the corresponding drug for 7 days.Body mass was monitored,open-field behavioral tests were performed,serum levels of orexin A(OXA)and orexin B(OXB)were detected by enzyme-linked immunosorbent assay(ELISA),the expression of hypothalamic orexin receptor 1(OX1R)was determined by immunohistochemistry,and hematoxylin-eosin(HE)staining was used to observe the pathologic changes in the hypothalamus of rats.Results(1)Before modeling,the growth trend of body mass of rats in each group was smooth,with no significant difference between groups;after modeling,except for the normal group,the growth rate of body mass of rats in each group slowed down or even declined;after 14 days of administration of Modified Banxia Shumi Decoction,the body mass of the Chinese medicine medium-dose group was significantly increased compared with that of the model group(P＜0.01).(2)Compared with the normal group,the model group showed an increase in the total distance of activity in the open field,the distance of activity in the central region and the number of times of entering the central region(P＜0.01),a significant increase in serum OXA and OXB contents(P＜0.01),a significant increase in the expression of hypothalamic OX1R(P＜0.01),and HE staining showed mild hyperplasia of the hypothalamic glial cells;compared with the model group,the total distance of activity in the open field,the distance of activity in the central region and the number of times entering the central region were reduced in the rats in the Chinese medicine medium-dose group and the Diazepam group(P＜0.01),the levels of serum OXA and OXB were significantly reduced(P＜0.01),the expression of hypothalamic OX1R was significantly reduced(P＜0.01),and the HE staining showed that a large number of neurons with perineurial interspace enlarged and the local glial cell hyperplasia.Conclusion Modified Banxia Shumi Decoction can improve insomnia and reduce anxiety in rats by down-regulating the levels of OXA and OXB in serum and the expression of OX1R in the hypothalamus.

Study on the Acupoint Selection and Medication Rules of Acupoint Application as An Advantageous Therapy in the Treatment of Stroke / 广州中医药大学学报

Objective To study the acupoint selection and medication rules of acupoint application as an advantageous therapy in treating stroke.Methods The clinical literature from CNKI,Wanfang,CBMdisc,and other databases were searched,and Excel 2013 was used to count the frequency of disease,acupoint selection,and medication,and to analyze the acupoint selection rules using SPSS 25.0 and SPSS Modeler.Results Finally,523 articles were included in the literature,among which,the literature on the treatment of post-stroke constipation with acupoint patch was the most,and the related literature was further screened to analyze the acupoint selection and medication rules,and it was concluded that the most frequently applied acupoints of acupoint application for the treatment of post-stroke constipation were Shenque(RN8),Tianshu(ST25),Zhongwan(RN12),Zusanli(ST36),and the acupoints were mainly taken from conception vessel,stomach meridian and gallbladder meridian,and the core prescriptions were Shenque,Tianshu,Zhongwan,Qihai(RN6),Guanyuan(RN4),Zusanli.For the treatment of post-stroke constipation,acupoint application is often used with Rhei Radix et Rhizoma,Aurantii Fructus Immaturus,Cortex Magnoliae Officinalis,Natrii Sulfas Exsiccatus and Borneolum Syntheticum,among which,warm and cold nature drugs are mainly used,and bitter drugs are most frequently used among five flavors,and most frequently enter to the spleen meridian;and the core prescription is Rhei Radix et Rhizoma,Aurantii Fructus Immaturus,Cortex Magnoliae Officinalis,Natrii Sulfas Exsiccatus and Borneolum Syntheticum.Conclusion Acupoint application is an advantageous treatment for treating post-stroke constipation.The selection of acupoints was based on the conception vessel and stomach meridian,and the medication used were mainly focusing on those with functions of unblocking the bowels and directing qi downward,supplemented by strengthening the spleen and benefiting qi,warming the meridians and nourishing the blood.

Application of multiplanar reconstruction and 3D printing in anterior cruciate ligament revision / 中南大学学报(医学版)

Objective:Anterior cruciate ligament injury is the most common type of knee joint ligament injury.Anterior cruciate ligament reconstruction has a high failure rate,with bone tunnel abnormalities as the most significant factor in these failures.Digital orthopedic technology can effectively develop implementation plans for the revision,thus increasing the success rate.This study aims to develop a surgical plan for anterior cruciate ligament revision by employing multiplanar reconstruction(MPR)for measuring bone tunnel position and diameter,and simulating bone tunnel creation via 3D printing preoperatively. Methods:A total of 12 patients who underwent anterior cruciate ligament revision at the Third Xiangya Hospital of Central South University between 2014 and 2021 were retrospectively studied.The data included patient demographics,preoperative formulated knee joint 3D printing models,and preoperative knee CT scans.The study measured the bone tunnel's diameter and position to guide the establishment of revision bone tunnels during surgery,reassessed the postoperative bone tunnels,and evaluated knee joint functional scores[including International Knee Documentation Committee Knee Evaluation Form(IKDC)score,Lysholm score,and Tegner exercise level score]. Results:Preoperative measurements revealed suboptimal femoral tunnels positions in 4 patients and tibial tunnels positions in 2 patients.MPR and 3D printing technology were used to guide the establishment of a new bone canal during surgery,and postoperative measurements were satisfactory for all patients.Preoperative measurements demonstrated the interclass correlation coefficient for femoral tunnels and tibial tunnels diameters were 0.843(P<0.05)and 0.889(P<0.001),respectively.Meanwhile,the intraclass correlation coefficient were 0.811(P<0.05)and 0.784(P<0.05),respectively.The intraoperative diameter of femoral and tibial tunnels showed excellent correlation with postoperative CT measurements,with intraclass correlation coefficient values of 0.995(P<0.001)and 0.987(P<0.001),respectively.All bone tunnel positions were within the normal range.At the final follow-up,knee joint function scores in all 12 patients improved significantly compared to pre-surgery(P<0.001),and the reoperation rate was zero. Conclusion:MPR and 3D printing technology can accurately measure the parameters of reconstructed anterior cruciate ligament bone tunnels.Personalized revision plans for patients with reconstruction failure enhances the success rate of revision surgery and improves patient prognosis.

Correlation between PIK3CA mutation and clinicopathological features and prognosis of breast cancer / 基础医学与临床

Objective To find the correlation between phosphatidylinositol kinase-3 catalytic subunit A gene(PIK3CA)mutation and pathological features as well as clinical prognosis of breast cancer.Methods The patho-logical data of 181 patients diagnosed with invasive breast cancer from January 2018 to January 2020 were collected.The estrogen receptor(ER),progestogen receptor(PR),human epidermal growth factor receptor-2(HER2),Ki67 were examined by immuno-histochemistry(IHC).Mutation of exon 9 and exon 20 of PIK3CA were examined by quantitative real-time PCR(qPCR).Results Among 181 cases of invasive breast cancer,70 cases had PIK3CA mutation with 31 cases(44.28%)showed exon 9 mutations and 39 cases(55.71%)showed exon 20 mutations.The difference between PIK3CA mutation and their distribution in molecular typing of breast cancer was statistically significant(P＜0.05).The expression of PIK3CA mutation in breast cancer with different Ki67 expression was sig-nificantly different(P＜0.05).There were 34 cases(48.57%)showed PIK3CA mutations in the HR+/HER2 group and 36 cases(51.43%)of non HR+/HER2 group mutations.There was a statistically significant difference in the distribution of PIK3CA mutations between 2 groups(P＜0.05).The death rate of PIK3CA mutation cases was higher than that of PIK3CA wild type cases(P＜0.05).Conclusions PIK3CA mutation is associated with molecular typ-ing,Ki67 increment index and prognosis of breast cancer.Detection of PIK3CA mutation provides potential support to the development of precise treatment of breast cancer patients.

Anlotinib inhibits proliferation and promotes apoptosis of human non-small cell lung cancer cell lines through miR-16-5p/PD-1 axis / 基础医学与临床

Objective To investigate the effect of Anlotinib on proliferation and apoptosis in non-small cell lung cancer(NSCLC)cells and its molecular mechanism.Methods Non-small cell lung cancer cell lines A549 and H1299 were incubated with Anlotinib,miR-16-5p agonist and/or PD-1 overexpression vector respectively.CCK-8 assay and EDU assay were applied to detect the proliferation.Flow cytometry was performed to detect the cell apop-tosis.The relative expression of miR-16-5 p in A549 and H1299 was detected by real-time quantitative polymerase chain reaction(RT-qPCR).The relative protein expression of PD-1 in A549 and H1299 was detected by Western blot assay.The interaction between miR-16-5p and PD-1 was determined by dual luciferase reporter assay.Finally,A549 cell xenograft model was established to assess the effect of Anlotinib on tumor growth in vivo.Results Anlotinib significantly increased miR-16-5p expression and decreased PD-1 expression in A549 cells and H1299 cells,inhibited cell proliferation and promoted apoptosis in a dose-dependent manner(P＜0.05).The highly-expressed miR-16-5p inhibited proliferation and promoted cell apoptosis(P＜0.05).Also,miR-16-5p targeted at PD-1 and negatively regulated PD-1 expression.Knockdown of PD-1 inhibited proliferation and pro-moted cell apoptosis(P＜0.05).PD-1 over-expression reversed the Anlotinib-mediated pro-proliferation and anti-apoptosis of miR-16-5p in A549 cells and H1299 cells(P＜0.05).Anlotinib significantly reduced tumor growth in vivo(P＜0.05).Conclusions Anlotinib may inhibit cell proliferation,anti-apoptosis,and reduce tumor growth for NSCLC,which is involved in miR-16-5p/PD-1 axis.

Effects of chidamide combined with PD-1 inhibitor on anti-tumor function of CD8+ T cells in mouse model of colorectal cancer / 解放军医学杂志

Objective To investigate the efficacy of histone deacetylase(HDAC)inhibitor chidamide combined with the PD-1 inhibitor on CD8+ T cells anti-cancer function in OVA-expressing MC38(MC38-OVA)colorectal-bearing mice.Methods Animal experiments:C57BL/6 tumor models were constructed by subcutaneously injecting MC38-OVA colorectal cancer cells into the back of mice.We randomized mice into control group,chidamide group,anti-PD-1 group and chidamide+anti-PD-1 group(20 each group).We monitored the tumor growth and animal survival rate of each group;we employed a flow-based method to detect the number and ratio of tumor-infiltrating CD8+ T cells,CD8+IFN-γ+ T cells,OVA antigen-specific CD8+ T cells,and the expression changes of regulatory T cells(Treg),myeloid-derived suppressor cells(MDSC),and tumor-associated macrophages(TAM).Cell experiments:We used a flow-based method to detect the apoptosis of CD8+ T cells and MC38-OVA tumor cells after 0,10,25,50,100,or 200 nmol/L chidamide treatment.The proliferation of CD8+ T cells and MC38-OVA tumor cells treated with 0 and 100 nmol/L chidamide was detected by Ki-67 antibody labeling and cell counting.To evaluate CD8+ T cell killing ability,we treated CD8+ T cells with various conditions(control group,chidamide group,anti-PD-1 group and chidamide+anti-PD-1 group)followed by co-culture with MC38-OVA tumor cells,using the flow-based method.In the condition that CD8+ T cells treated with 0 and 100 nmol/L chidamide co-cultured with the same number of MC38-OVA tumor cells,the expression of CD107a was detected by flow cytometry.Results Compared with control group,the tumor growth was inhibited(P<0.05)while the survival rate was improved(P<0.01)in chidamide+anti-PD-1 group.The number of tumor-infiltrating CD8+ T cells was significantly higher in chidamide group,anti-PD-1 group and chidamide+anti-PD-1 group than that in control group(P<0.05).Nonetheless,the ratio and levels of CD8+IFN-γ+ and OVA antigen-specific CD8+ T cells were significantly higher in chidamide+anti-PD-1 group than those in other groups(P<0.05).The in vitro experiment results showed that chidamide could enhance the killing ability of CD8+ T cells and the expression of CD107a.Conclusion Chidamide combined with PD-1 inhibitor significantly enhanced the number and function of tumor-infiltrating CD8+ T cells and increased antigen-specific CD8+ T cells,which will provide a theoretical and experimental basis for the combination of chidamide in clinical solid tumor immunotherapy.

Research progress on the mechanism of metachronous gastric cancer after endoscopic submucosal dissection and Helicobacter pylori eradication in early gastric cancer / 解放军医学杂志

Helicobacter pylori(HP)infection is a Class Ⅰ carcinogen in gastric cancer,closely related to the occurrence of gastric cancer.Many studies have shown that HP eradication has a preventive effect on gastric cancer.However,2.7%-6.1%of patients with early gastric cancer who have been eradicated after endoscopic submucosal dissection(ESD)can still develop metachronous gastric cancer(MGC),and the mechanism of its occurrence is still unclear.In this review,the atrophy of gastric mucosa and intestinal metaplasia cannot be completely reversed after HP eradication,the excessive proliferation of gastric mucosa epithelial cells,the accumulation of genetic abnormalities,the homeostasis imbalance of the epigenetic group,changes in immune microenvironment,the abnormality of stem cells in gastric mucosa,chromatin accessibility,and changes in chromosome remodeling were discussed in the mechanism of carcinogenesis caused by the above molecular changes after ESD and HP eradication in early gastric cancer.

Construction and validation of a scoring model for pathogen characteristics and short-term prognosis risk prediction of candidemia / 解放军医学杂志

Objective To analyze the pathogenic characteristics and drug sensitivity of candidaemia,and construct a short-term mortality risk prediction scoring model.Methods The clinical data of patients with candidaemia admitted to the 909 Hospital of Joint Logistics Support Force from January 2011 to December 2020 were retrospectively analyzed,and the composition of pathogen composition,drug sensitivity test results and incidence of hospitalized patients were analyzed.324 cases of candidaemia were randomly divided into modeling group(190 cases)and validation group(134 cases),and the risk factors were screened by binary logistic regression.According to the odds ratio(OR)score,the 30 day mortality risk prediction scoring model was constructed,and the predictive performance of the model was verified both in modeling and validation groups.Results 356 strains of Candida including 126 strains of C.albicans(35.39%),79 strains of C.tropicalis(22.19%),74 strains of C.parapsilosis(20.79%),48 strains of C.glabrata(13.48%),14 strains of C.guilliermondii(3.93%),8 strains of C.krusei(2.25%),and 7 strains of other Candida(1.97%)were detected in 336 patients with candidemia.The incidence of candidaemia among hospitalized patients increased from 0.20 ‰ in 2011 to 0.48 ‰ in 2020.The resistance rate of candida to amphotericin B was significantly lower than that of fluconazole,voriconazole and itraconazole(P＜0.05).Among the 324 cases included in the model,95 patients died in 30 days after diagnosis,and the mortality rate was 29.32%.The proportion of males,fever,and parenteral nutrition in modeling group was significantly higher than that in validation group(P＜0.05),while the proportion of chronic lung disease and surgical history within one month were lower than those in validation group(P＜0.05).Logistic regression analysis showed that chronic renal failure,mechanical ventilation,severe neutropenia,failure to receive anti-fungal treatment within 72 hours,and APACHE Ⅱ≥20 were risk factors for short-term death of candidaemia,the OR values were 3.179,1.970,2.979,2.080,and 2.399,and the risk scores were 6,4,6,4,and 5,respectively.The area under the curve(AUC)of the risk scoring model for modeling group was 0.792(95%CI 0.721-0.862),and the result of Hosmer-Lemeshow(H-L)test was P=0.305;The AUC of validation group was 0.796(95%CI 0.735-0.898),and the H-L test result was P=0.329.A risk score≤8 indicated a low risk group for short-term mortality,a score of 9-15 indicated a medium risk group,and a score≥16 indicated a high risk group.Conclusions The incidence of candidemia in hospitalized patients is increasing and the mortality is high.The risk prediction score model can effectively predict the short-term prognosis and facilitate the early identification of the prognosis.

Research progress on the effect of α7 nicotinic acetylcholine receptor on perioperative neurocognitive function / 解放军医学杂志

α7 nicotinic acetylcholine receptor(α7nAChR)is widely expressed in the central nervous system and immune system,and plays a neuro-immunoregulatory role.On the one hand,α7nAChR is involved in the transmission of neurotransmitters,the conduction of excitatory signals and the maintenance of synaptic plasticity,which is of great significance for maintaining the normal and stable neurocognitive function.On the other hand,as an important part of the cholinergic anti-inflammatory pathway,α7nAChR is involved in the regulation of physiological and pathological processes such as inflammatory response,oxidative stress,apoptosis and autophagy in the central system,and plays an immunomodulatory and neuroprotective role,thus being potential target for improving perioperative neurocognitive function.This article reviews the biological characteristics of α7nAChR and its effect on perioperative neurocognitive function,in order to provide ideas and methods for clinical improvement of perioperative neurocognitive function in surgical patients.

Association between index-ring finger length ratio and polymorphisms of 6 phalange-bone development related genes / 解剖学报

Objective To investigate the association of 13 single nucleotide polymorphism(SNP)sites in 6 phalange-bone development related genes[fibroblast growth factor receptor 2(FGFR2),indian hedgehog signaling molecule(IHH),Msh homeobox 1(MSX1),Runx family transcription factor 2(RUNX2),SRY-box transcription factor 9(SOX9),Wnt family member 5A(WNT5A)]with human index-ring finger length ratio(2D∶4D).Methods Digital cameras were used to take frontal photographs of the hands of 731 college students(358 males and 373 females)in Ningxia,and image analysis software was used to mark anatomical points and measure finger lengths of index(2th)and ring(4th);genotyping of 13 SNP sites(rs1047057,rs755793,rs41258305,rs3731881,rs3100776,rs12532,rs3821949,rs45585135,rs3749863,rs1042667,rs12601701,rs1829556,rs3732750)for 6 genes by multiplex PCR;One-Way ANOVA or independent sample t-test indirectly assessed the association between 2D∶4D and 13 SNP sites.Results Both left and right hand 2D∶4D were significantly higher in females than males in Ningxia college students(all P<0.01);no statistically significant differences in genotype and allele frequencies of the 13 SNP sites among different sexes(all P>0.05);among different sexes,male left hand 2D∶4D was significantly associated with the genotype of SOX9 gene rs12601701 site(P<0.05)and right hand 2D∶4D was significantly associated with the genotype of WNT5A gene rs1829556 site(P<0.05);the female right hand 2D∶4D was significantly associated with the MSX1 gene rs12532(P<0.01)and rs3821949(P<0.05)sites genotypes.Conclusion SOX9(rs12601701),WNT5A(rs1829556)and MSX1(rs12532 and rs3821949)gene polymorphisms may be associated with the formation of 2D∶4D in Ningxia population.