Mechanism study of Qingre huashi decoction in the treatment of gastric cancer by up-regulating miRNA-155 and inhibiting Wnt/β-catenin signaling pathway / 中国药房

OBJECTIVE To study the mechanism of Qingre huashi decoction in the treatment of gastric cancer by intervening in miRNA-155 and inhibiting Wnt/β-catenin signaling pathway. METHODS Thirty nude mice were randomly divided into model group， control group （0.004 g/kg cisplatin+0.02 g/kg fluorouracil）， overexpression group， Qingre huashi prescription low-dose， medium-dose and high-dose groups （2.71， 5.43， 10.86 g/kg）， with 5 mice in each group. The overexpression group was inoculated with miRNA-155 AGS cell line， and the other groups were inoculated with AGS cells to induce tumor-bearing gastric cancer model. The control group was given relevant medicine intraperitoneally， and other groups were given relevant medicine or normal saline intragastrically， once a day， for 3 consecutive weeks. The weight of tumor tissue in nude mice was determined； the pathological morphology of tumor tissue was observed； the miRNA-155 expression， mRNA and protein expressions of Wnt7， β-catenin and T- cell factor-4（TCF-4） in tumor tissue were detected. RESULTS Compared with the model group， the tumor weights of nude mice in the control group， the overexpression group and Qingre huashi decoction high-dose group were significantly reduced （P＜0.05）； mRNA and protein expressions of Wnt7， β -catenin and TCF-4 were significantly decreased （P＜0.05）， while miRNA-155 expression was increased significantly （P＜0.05）. Tumor cells exhibited varying degrees of loose arrangement， shallow nuclear staining， and necrotic foci. CONCLUSIONS Qingre huashi decoction can inhibit the protein and mRNA expressions of Wnt7， β-catenin and TCF-4 in Wnt/β-catenin signaling pathway by up-regulating miRNA-155， thus inhibiting the tumor growth of tumor-bearing nude mice.

Efficacy and safety of image-guided hypofractionated intensity-modulated radiotherapy combined with contralateral esophageal protection in treatment of unresectable stage Ⅲ non-small cell lung cancer / 肿瘤研究与临床

Objective:To explore the efficacy and adverse reactions of image-guided hypofractionated intensity-modulated radiotherapy (Ig-HypoRT) conbined with contralateral esophageal protection in treatment of patients with unresectable stage Ⅲ non-small cell lung cancer (NSCLC).Methods:The clinical data of 45 patients with unresectable stage Ⅲ NSCLC who were admitted to Xuzhou Cancer Hospital from January 2016 to January 2019 were retrospectively analyzed. Patients received induction chemotherapy with a platinum-based dual-drug combination regimen, followed by Ig-HypoRT with a total dose of tumor of 60-63 Gy/12- 18 times at 3.5-5.0 Gy/time. Contralateral esophagus was delineated as an organ at risk during radiotherapy, limiting V 45 Gy≤1.8 cc and V 55 Gy ≤0.4 cc. Patients' efficacy, survival and the occurrence of adverse reactions were observed. Results:Among 45 patients, there were 9 cases of complete remission, 31 cases of partial remission, 4 cases of stable disease and 1 case of disease progression, and the effective rate was 88.8% (40/45). The median follow-up time was 34 months, 45 patients had a median overall survival (OS) time of 25.0 months (95% CI 21.7-28.8 months), with 1-, 2-, and 3-year OS rates of 78.9%, 56.8% and 47.7%, respectively; the median progression-free survival (PFS) time was 18.5 months (95% CI 15.0-22.0 months), with 1-, 2- and 3-year PFS rates of 59.8%, 32.6% and 18.6%, respectively. The 3-year local recurrence rate was 9% (4/45). The incidence of grade 1-2 radioactive esophagitis was 80% (36/45); the incidence of grade 1-2 chest pain was 20% (9/45). The incidence of grade 3-4 adverse reactions were 13% (6/45), including 7% (3/45) of grade 3 pulmonary atelectasis, 4% (2/45) of grade 3 radioactive pneumonia, and 2% (1/45) of grade 4 hemoptysis. Conclusions:Ig-HypoRT combined with contralateral esophageal protection for unresectable stage Ⅲ NSCLC can improve survival rate and reduce esophageal adverse reactions of patients.

Construction and validation of a prognostic model for colon cancer based on inflammatory response-related genes / 肿瘤研究与临床

Objective:To screen the differentially expressed genes (DEG) related to inflammatory response associated with the prognosis of colon cancer based on the bioinformatics approach, and to construct and validate a prognostic model for colon cancer.Methods:RNA sequencing and clinical data of 472 colon cancer patients and normal colon tissues of 41 healthy people were retrieved from the Cancer Genome Atlas (TCGA) database. Gene expression related to prognosis of colon cancer and clinical data were retrieved from the International Cancer Genome Consortium (ICGC) database. The retrieval time was all from the establishment of library to November 2022. A total of 200 genes associated with inflammatory response obtained from the Gene Set Enrichment Analysis (GSEA) database were compared with the RNA sequencing gene dataset of colon cancer and normal colon tissues obtained from the TCGA database, and then DEG associated with inflammatory response were obtained. The prognosis-related DEG in the TCGA database were analyzed by using Cox proportional risk model, and the inflammatory response-related DEG were intersected with the prognosis-related DEG to obtain the prognosis-related inflammatory response-related DEG. The prognostic model of colon cancer was constructed by using LASSO Cox regression. Risk scores were calculated, and colon cancer patients in the TCGA database were divided into two groups of low risk (< the median value) and high risk (≥the median value) according to the median value of risk scores. Principal component analysis (PCA) was performed on patients in both groups, and survival analysis was performed by using Kaplan-Meier method. The efficacy of risk score in predicting the overall survival (OS) of colon cancer patients in the TCGA database was analyzed based on the R software timeROC program package. Clinical data from the ICGC database were applied to externally validate the constructed prognostic model, and patients with colon cancer in the ICGC database were classified into high and low risk groups based on the median risk score of patients with colon cancer in the TCGA database. By using R software, single-sample gene set enrichment analysis (ssGESA), immunophenotyping difference analysis, immune microenvironment correlation analysis, and immune checkpoint gene difference analysis of immune cells and immune function were performed for prognosis-related inflammation response-related DEG in the TCGA database.Results:A total of 60 inflammatory response-related DEG and 12 prognosis-related DEG were obtained; and 6 prognosis-related inflammatory response-related DEG (CCL24, GP1BA, SLC4A4, SRI, SPHK1, TIMP1) were obtained by taking the intersection set. LASSO Cox regression analysis showed that a prognostic model for colon cancer was constructed based on 6 prognosis-related inflammatory response-related DEG, and the risk score was calculated as = -0.113×CCL24+0.568×GP1BA+ (-0.375)×SLC4A4+(-0.051)×SRI+0.287×SPHK1+0.345×TIMP1. PCA results showed that patients with colon cancer could be better classified into 2 clusters. The OS in the high-risk group was worse than that in the low-risk group in the TCGA database ( P < 0.001); the area of the curve (AUC) of the prognostic risk score for predicting the OS rates of 1-year, 3-year, 5-year was 0.701, 0.685, and 0.675, respectively. The OS of the low-risk group was better than that of the high-risk group in the ICGC database; AUC of the prognostic risk score for predicting the OS rates of 1-year, 2-year, 3-year was 0.760, 0.788, and 0.743, respectively. ssGSEA analysis showed that the level of immune cell infiltration in the high-risk group in the TCGA database was high, especially the scores of activated dendritic cells, macrophages, neutrophils, plasmacytoid dendritic cells, T helper cells, and follicular helper T cells in the high-risk group were higher than those in the low-risk group, while the score of helper T cells 2 (Th2) in the high-risk group was lower compared with that in the low-risk group (all P < 0.05); in terms of immune function, the high-risk group had higher scores of antigen-presenting cell (APC) co-inhibition, APC co-stimulation, immune checkpoint, human leukocyte antigen (HLA), promotion of inflammation, parainflammation, T-cell stimulation, type Ⅰ interferon (IFN) response, and type ⅡIFN response scores compared with those in the low-risk group (all P < 0.05). The results of immunophenotyping analysis showed that IFN-γ-dominant type (C2) had the highest inflammatory response score, and the differences were statistically significant when compared with trauma healing type (C1) and inflammatory response type (C3), respectively (all P < 0.05). Immune microenvironment stromal cells and immune cells were all positively correlated with prognostic risk scores ( r values were 0.35 and 0.21, respectively, both P < 0.01). The results of immune checkpoint difference analysis showed there was a statistically significant difference in programmed-death receptor ligand 1 (PD-L1) expression level between high-risk group and low-risk group ( P = 0.002), and PD-L1 expression level was positively correlated with prognostic risk score ( r = 0.23, P < 0.01). Conclusions:Inflammatory response-related genes may play an important role in tumor immunity of colon cancer and can be used in the prognostic analysis and immunotherapy of colon cancer patients.

Application of "ABC" three line perforator locating method for free anterolateral perforator flap of calf / 中华显微外科杂志

Objective:To explore the feasibility of an "ABC" three line perforator locating method in design and harvest of free anterolateral perforator flap of calf.Methods:Between March 2021 and November 2021, 42 patients with 62 wounds on hand and foot were treated in the Department of Hand Surgery, Suzhou Ruihua Orthopaedic Hospital. The "ABC" three line perforator locating method was applied to determine the location and source of perforating branch before operation and to guide the design and harvest of flap during operation in wound reconstruction. Among the 42 patients, 24 had the injury of single digit, 7 had the injuries with 2 digits, 4 with 3 digits, 1 with 4 digits, 1 of the first web, 1 in the wrist, 2 of the great toe, 1 of second toe and 1 in dorsal foot. The sizes of soft tissue defect were 1.5 cm×2.0 cm-3.0 cm×14.0 cm. The sizes of the flaps were 2.0 cm×2.5 cm-3.5 cm×15.0 cm. All donor sites were sutured directly. In the follow-up, sensations of flaps were evaluated following the sensory function evaluation standard of British Medical Research Council(BMRC), and the recovery of the donor and recipient sites was evaluated by the flap comprehensive evaluation scale. Regular follow-up were scheduled at outpatient clinic.Results:A total of 162 perforators were located before operation. There were 95 perforating branches being explored in the operation, of which 5 patients had 1 extra perforating branch than that located before surgery. Seventy-six perforating branches were found consistent with preoperative localisation, with a coincidence rate of 84.4%(76/90). Sixty-four perforating branches were found consistent with the preoperative source with an accuracy rate of 84.2%(64/76). All the 62 flaps survived without a vascular compromise. Follow-up lasted for 6-10(mean 7.1) months. The colour and texture of the flaps were excellent. The flaps were thin and wear-resistant. The sensory function of the flaps was evaluated at S 1-S 3 by BMRC. Comprehensive evaluation scale of flap was excellent in 38 patients and good in 4 patients. Conclusion:"ABC" three line perforator locating method in design of free anterolateral calf flap is a feasible and an ideal auxiliary method in surgical practice. It combines anatomical knowledge, clinical experience and Doppler ultrasound localisation as well as accurately guides the location and source prediction of perforator before surgery.

Aortic banding for refractory endoleaks after endovascular abdominal aortic aneurysm repair / 中华普通外科杂志

Objective:To summarize the safety and efficacy of aortic banding in the treatment of refractory endoleaks after endovascular abdominal aortic aneurysm repair (EVAR).Methods:The clinical and follow-up data of 10 patients with refractory endoleaks EVAR undergoing aortic banding at Peking University People's Hospital from Jun 2019 to Aprl 2022 were retrospectively analyzed.Results:The aortic banding was indicated for type Ⅰ endoleak in 6 patients, type Ⅱ endoleak in 3 patients and internal tension in 1 patient with persistent aneurysm enlargement or rupture. The surgical procedure was based on laparotomy. The proximal aortic neck was exposed and re-fixation with artificial strip to prevent bleeding. The surgical procedures was successful in all the 10 cases without residual endoleak or re-bleeding. The post-operative contrast-enhanced ultrasonography revealed neither new-onset endoleak nor occlusion of stent-grafts. Perioperative complications included one case of delayed wound healing and one case of incomplete ileus. No perioperative deaths occurred. Midterm follow-up was achieved in 10 patients with a mean follow-up time of 13 months. No recurrence of endoleak was found. One patient underwent endovascular repair for independent thoracic aortic aneurysm 6 months after surgery. There were no other aorta-related secondary surgeries or aortic-related deaths.Conclusion:Aortic banding for refractory endoleaks after EVAR is minimally invasive and reliable. It can effectively eliminate the refractory endoleaks, and reduce the risks of aortic-related secondary surgery or death.

Predictive value of serum neutrophil gelatinase-associated lipocalin for acute kidney injury in high-risk elderly patients / 中华老年医学杂志

Objective:To analyze the predictive value of neutrophil gelatinase-associated lipocalin(NGAL)in high-risk elderly patients with acute kidney injury(AKI).Methods:A retrospective study was conducted to collect 183 patients over 65 years old in the Department of Geriatrics, the First Affiliated Hospital of Nanjing Medical University from January 2018 to October 2019.The patients were combined with at least one risk factor.The diagnostic effect of NGAL for AKI prediction in high-risk patients was evaluated.According to the initial serum creatinine(SCr)and basic glomerular filtration rate(eGFR), the patients were divided into chronic kidney disease(CKD)group and non-CKD group.The optimal diagnostic threshold for A-on-C is determined by determining the area under the subject curve(AuROC). Univariate and independent predictors multivariate regression analysis was used to assess the risk of AKI.Results:The serum NGAL(NGAL)level in AKI group was higher than that in non-AKI group[702.5 μg/L(499.2, 813.2) vs.233.9 μg/L(147.2, 315.7), Z=8.002, P<0.001]. In CKD patients, serum NGAL in AKI group was higher than that in non-AKI group[1033 μg/L(845.5, 1447) vs.288.2 μg/L(221.4, 423.3), Z=4.867, P<0.001]. In all patients, model 3 with four variables showed better AKI prediction ability than model 0, 1 and 2( R2=0.743, P<0.001). In the CKD group, the AuROC of serum NGAL for AKI prediction was larger than that of CYS-C group, whereas in the non-CKD group, the AuROC of serum NGAL for AKI prediction was smaller than that of CYS-C group. Conclusions:Serum NGAL may serve as a useful biomarker for AKI prediction in AKI high-risk elderly patients.Especially in patients with CKD, Serum NGAL has a better predictive value for AKI than traditional indicators.

Efficacy of chemoradiotherapy versus surgery in cervical esophageal cancer: a population-based competing risk analysis / 中华放射肿瘤学杂志

Objective:To evaluate the value of chemoradiotherapy and surgery in cervical esophageal cancer (CEC).Methods:Data of 459 patients with CEC from 2004 to 2017 were collected and retrospectively analyzed from the surveillance, epidemiology, and end results (SEER) database of National Cancer Institute (US). All patients were divided into the chemoradiotherapy group ( n=379) and surgery group ( n=80) according to the treatment methods. Survival analysis was performed by Kaplan-Meier method and survival curve was drawn. Multivariate survival analysis was conducted by Cox proportional hazards regression model. The death rate of different causes between two groups was calculated by cumulative incidence function (CIF). The differences of death rate between two groups were evaluated by Fine-Gray competing risk model. By analyzing the clinical characteristics and survival of CEC patients, the overall survival (OS) was compared between the surgery and chemoradiotherapy groups. Results:The 2- and 5-year survival rates in the chemoradiotherapy group were 43.1% and 22.4%, while those of the surgical group were 46.8% and 26.0%, respectively. No significant difference was observed in the OS between the chemoradiotherapy and surgery groups ( P=0.750). Cox multivariate analysis showed that treatment (surgery group vs. chemoradiotherapy group) was not an independent prognostic factor for OS. Based on the results of competing risk analysis, the risk of esophageal cancer-specific death in the chemoradiotherapy group was higher than that in the surgery group, and the difference was statistically significant between two groups ( P<0.001). The risk of other cause-specific death in the chemoradiotherapy group was lower than that in the surgery group ( P<0.001). The proportion of patients who died of oral, oropharyngeal, hypopharyngeal and laryngeal diseases in the surgery group was significantly higher than that in the chemoradiotherapy group(all P<0.001). Conclusions:No significant difference is observed in the OS of CEC patients treated with chemoradiotherapy or surgery. In the surgery group, the risk of esophageal cancer-specific death is lower, whereas the risk of other cause-specific death is higher compared with those in the chemoradiotherapy group.

Phase II trial of hippocampal avoidance whole-brain irradiation with simultaneous integrated boost for treatment of brain metastases of lung cancer / 中华放射肿瘤学杂志

Objective:To evaluate the efficacy and safety of hippocampal avoidance whole-brain irradiation with simultaneous integrated boost in the treatment of brain metastases of lung cancer.Methods:Forty lung cancer patients with brain metastases who received whole-brain radiotherapy with simultaneous integrated boost and hippocampal avoidance in Cancer Hospital, Chinese Academy of Medical Sciences from 2014 to 2020 were enrolled in this study. Brain MRI, survival follow-up and evaluation of side effects were performed before radiotherapy and at 1, 3, 6 and 12 months after radiotherapy, respectively. Overall survival (OS), progression-free survival (PFS) and changes in cognitive function were analyzed. Continuous data were described as Mean ± SD. Categorical data were described by frequency and composition ratio or percentage. Survival analysis was conducted by Kaplan-Meier method. Influencing factors of survival were identified by univariate and multivariate Cox's regression analyses.Results:A total of 40 patients were enrolled in the study. The median follow-up time was 14.2 months and the median OS, PFS and intracranial PFS of all patients were 14.8 months, 6.7 months and 14.8 months, respectively. Multivariate analysis showed that male gender and newly diagnosed stage Ⅳ disease were associated with worse OS and PFS, respectively. The Hopkins verbal learning test-revised (HVLT-R) scores at baseline and 1, 3 and 6 months after radiotherapy were 21.94±2.99, 20.88±3.12, 20.03±3.14, and 19.78±2.98, respectively. The HVLT-R score at 6 months after radiotherapy was decreased by approximately 9.8% compared with the baseline. No grade 3 or above toxic and side effect occurred in the entire cohort.Conclusion:Hippocampal avoidance whole-brain irradiation with simultaneous integrated boost is a safe and effective treatment for brain metastases of lung cancer, which is expected to reduce the impact of radiotherapy on cognitive function.

Research progress on image standard database of artificial intelligence-assisted radiotherapy for lung cancer / 中华放射肿瘤学杂志

Lung cancer is the malignant tumor with the highest mortality rate in the world. Radiotherapy plays an important role in the comprehensive treatment of lung cancer. With the continuous advancement of radiotherapy technology and equipment, it has become one of the effective therapeutic options for lung cancer. In recent years, artificial intelligence technology has developed rapidly and has been widely applied in clinical practice, especially in the diagnosis and treatment of lung cancer imaging. The image database can be obtained by sorting and summarizing the images, which can be used in clinical work and scientific research. In this article, the application of artificial intelligence in lung cancer radiotherapy imaging and lung cancer imaging database was reviewed, aiming to provide reference for the construction of artificial intelligence radiotherapy imaging database for lung cancer.

Antibacterial copper sulfide/graphene oxide nanosheets composite film promotes angiogenic and osteogenic differentiation in vitro / 中华创伤骨科杂志

Objective:To investigate whether the antibacterial copper sulfide (CuS)/graphene oxide (GO) nanosheets composite film can promote angiogenesis and osteogenesis in vitro. Methods:GO and CuS/GO nanosheets were synthesized and mixed into polyvinyl alcohol (PVA)/carboxymethyl cellulose (CMC) hydrogel films. The study was conducted in 4 groups: PVA/CMC/GO, PVA/CMC/CuS/GO, PVA/CMC (only PVA/CMC-based film) and blank control (no material). The PVA/CMC, PVA/CMC/GO and PVA/CMC/CuS/GO films were characterized by electron scanning microscopy and energy dispersive spectrometer. The biocompatibility of different films (PVA/CMC/CuS/GO films with concentrations of CuS/GO nanotablets of 0, 50, 100, 200, 400, and 800 μ g/mL) was evaluated by CCK-8, live/dead cell staining, and hemolysis test. The angiogenesis was evaluated by cell migration and tube forming test in vitro. Alkaline phosphatase and alizarin red staining were used to evaluate osteogenesis in vitro, and the expression of osteogenic genes was measured by immunofluorescence staining and RT-qPCR. In addition, the bacterial plate counting method and bacteriostatic circle method were used to evaluate the antibacterial activity of films. Results:In the PVA/CMC/GO and PVA/CMC/CuS/GO groups, the surface of the PVA/CMC-based film was smooth and flat whereas the nanosheets composite films were irregularly flaky and convex. The biosafety experiments showed that the PVA/CMC-based film composited with GO or CuS/GO nanosheets at the concentration of 100 μg/mL had good biocompatibility. The results of angiogenesis in vitro showed that the migration ratio of HUVEC cells in the PVA/CMC/CuS/GO group was significantly better than those in the PVA/CMC/GO, PVA/CMC and control groups ( P<0.001). In the experiment of tube forming area and length, the PVA/CMC/CuS/GO group was significantly better than the PVA/CMC/GO, PVA/CMC and control groups ( P<0.001). The osteogenic differentiation in vitro displayed that the alkaline phosphatase and alizarin red staining of MC3T3-E1 cells in the PVA/CMC/CuS/GO group were significantly better than those in the PVA/CMC/GO, PVA/CMC and control groups ( P<0.001). In addition, the fluorescence intensity of immunofluorescence staining in alkaline phosphatase and type Ⅰcollagen on MC3T3-E1 cells, and the mRNA expression levels of osteogenic related genes including alkaline phosphatase, bone morphogenetic protein 2, osteocalcin and osteopontin in the PVA/CMC/CuS/GO group were significantly higher than those in the PVA/CMC/GO, PVA/CMC and control groups ( P<0.001). The antibacterial assay showed that the PVA/CMC/CuS/GO group had a significantly greater antibacterial activity and a significantly larger inhibition zone against Gram-positive bacteria and Gram-negative bacteria than the PVA/CMC/GO, PVA/CMC and control groups ( P< 0.001). Conclusions:PVA/CMC films composited with GO or CuS/GO nanosheets demonstrate ideal biocompatibility and antibacterial properties which promote angiogenesis and osteogenic differentiation in vitro. In particular, antibacterial PVA/CMC/CuS/GO composite films with the coupling function of angiogenesis and osteogenesis are expected to provide a new strategy for infectious bone defects.

Mechanism of Bielong Ruangan decoction in treatment of liver cancer based on network pharmacology and molecular docking / 中国医师杂志

Objective:To explore the key targets and mechanism of Bielong Ruangan decoction in the treatment of liver cancer based on network pharmacology and molecular docking.Methods:Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) database, PubChem database and PharmMapper database were used to search and screen the chemical components and related targets of Bielong Ruangan decoction and the targets of liver cancer diseases. The network diagram of " Bielong Ruangan decoction-traditional Chinese medicine-active ingredient-predicted target-disease" was constructed; Protein-protein interaction (PPI) network were analyzed through String database; gene ontology (GO) enrichment analysis was performed through WebGestalt database; Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis was carried out through KEGG Orthology Based Annotation System (KOBAS) database; Molecular docking of the active components and core target proteins of Bielong Ruangan decoction was carried out by using PyMOL, Auto DockVina and other software.Results:Bielong Ruangan decoction had 67 active components, 154 liver cancer targets and 244 pathways. According to the analysis of network pharmacology, Bielong Ruangan decoction may play an anti-cancer role through key targets such as epidermal growth factor receptor (EGFR), mitogen activated protein kinase 1 (MAPK1), estrogen receptor 1 (ESR1), MAPK8, serine threonine protein kinase 1 (AKT1), MAPK14, cysteine protease 3 (CASP3), cyclin-dependent kinase 2 (CDK2), bone morphogenetic protein 2 (BMP2), aldose reductase (AKR1B1) and other key targets. KEGG enrichment analysis showed that the treatment of liver cancer by Bielong Ruangan decoction involved the regulation of vascular endothelial growth factor (VEGF) signaling pathway, tumor necrosis factor (TNF) signaling pathway, thyroid hormone signaling pathway, T cell receptor signaling pathway and other pathways. The results of molecular docking showed that the binding energy of all compounds to protein was less than -5.6 kcal/mol, indicating that each compound and each protein could bind well.Conclusions:Bielong Ruangan decoction participates in the treatment of liver cancer through " multi-component, multi-target and multi-channel" ways, and plays an anti-cancer role mainly by regulating the proliferation and invasion of tumor cells and tumor inflammatory microenvironment.

Clinical features of three children with severe COVID-19 encephalopathy and literature review / 中国小儿急救医学

Objective:To analyze the clinical characteristics, diagnosis and treatment of 3 children with severe COVID-19 encephalopathy, aiming to improve the clinicians′ understanding of the disease.Methods:The clinical features, laboratory examinations, imaging data and diagnosis as well as treatment process of 3 cases of severe COVID-19 encephalopathy admitted to the Pediatric Intensive Care Unit of Shengjing Hospital of China Medical University from December 1, 2022 to December 31, 2022 were retrospectively analyzed.Results:Among the 3 patients, 2 were female, age was 2-11 years old, all of them had 2-3 days of medical history.All of them had clinical manifestations of high fever(≥40 ℃), convulsions and consciousness disorders, nucleic acid and antigen tests of SARS-CoV-2 were positive, and mycoplasma pneumonia IgM antibody was positive in 1 case.Within 24 hours after admission, the levels of white blood cells were basically normal, neutrophil fraction was dominant, and procalcitonin was significantly increased.Total T cells and NK cells in the blood of the three patients were significantly decreased, and the levels of blood ammonia, blood glucose and bilirubin were basically normal.During the early stage of the disease, the cell counts of the cerebrospinal fluid was normal in all three patients, the protein level was significantly increased, and there were new symmetrical lesions on head magnetic resonance imaging in 3 patients.After symptomatic treatment and immunotherapy including early use of hormone, human gamma globulin and plasma exchange, all patients were survived, but had different degrees of new dysfunction of the nervous system.Conclusion:Severe COVID-19 encephalopathy can occur in the acute phase of SARS-CoV-2 infection, mostly manifested as high fever, convulsions and severe disturbance of consciousness, combining with multiple organ dysfunction and irreversible nervous system damage.Early supportive treatment, brain protective treatment and immunotherapy are helpful to improve the prognosis of the patients.

Clinical features of three children with severe COVID-19 encephalopathy and literature review / 中国小儿急救医学

Objective:To analyze the clinical characteristics, diagnosis and treatment of 3 children with severe COVID-19 encephalopathy, targeted to improve the clinicians′ understanding of the disease.Methods:The clinical features, laboratory examinations, imaging data and diagnosis and treatment process of 3 cases of severe COVID-19 encephalopathy admitted to the Pediatric Intensive Care Unit of Shengjing Hospital of China Medical University from December 1, 2022 to December 31, 2022 were retrospectively analyzed.Results:Among the 3 patients, 2 were female, age was 2-11 years old, all of them had 2-3 days of medical history, all of them had clinical manifestations of high fever(≥40 ℃), convulsions and consciousness disorders, nucleic acid and antigen tests of SARS-CoV-2 were positive, and mycoplasma pneumonia IgM antibody was positive in 1 case.Within 24 hours after admission, the levels of white blood cells were basically normal, neutrophil fraction was dominant, and procalcitonin was significantly increased.Total T cells and NK cells in the blood of the three patients were significantly decreased, and the levels of blood ammonia, blood glucose and bilirubin were basically normal.In the early stage of the disease, the cell counts of the cerebrospinal fluid was normal in all the three patients, the protein level was significantly increased, there were new symmetrical lesions on head magnetic resonance imaging in 3 patients.After symptomatic treatment and immunotherapy including early use of hormone, human gamma globulin and plasma exchange, all the patients were survived, but had different degrees of new dysfunction of the nervous system.Conclusion:Severe COVID-19 encephalopathy can occur in the acute phase of SARS-CoV-2 infection, mostly manifested as high fever, convulsions and severe disturbance of consciousness, combined with multiple organ dysfunction and irreversible nervous system damage.Early supportive treatment, brain protective treatment and immunotherapy are helpful to improve the prognosis of patients.

Development and characteristics of automatic ash-removal heat-sensitive moxibustion device / 中国针灸

An automatic ash-removal heat-sensitive moxibustion device was developed, which could keep relatively constant temperature of heat-sensitive moxibustion, and realize the automatic ignition and automatic ash removal of moxa sticks during heat-sensitive moxibustion. The automatic ash-removal heat-sensitive moxibustion device comprises a bracket and a moxibustion box fixed on the top of the bracket; the bracket is composed of a base and a movable telescopic arm. This device can solve the problems of temperature instability, moxa ash blocking heat transfer and moxa ash falling during heat-sensitive moxibustion, avoiding the scalding caused by moxa ash falling, and reduce the workload of medical staff.

The expression and function of PD-L1 in CD133(+) human liver cancer stem-like cells / 中华肿瘤杂志

Objective: To investigate the expression of programmed death protein-ligand 1 (PD-L1) in liver cancer stem-like cells (LCSLC) and its effect on the characteristics of tumor stem cells and tumor biological function, to explore the upstream signaling pathway regulating PD-L1 expression in LCSLC and the downstream molecular mechanism of PD-L1 regulating stem cell characteristics, also tumor biological functions. Methods: HepG2 was cultured by sphere-formating method to obtain LCSLC. The expressions of CD133 and other stemness markers were detected by flow cytometry, western blot and real-time quantitative polymerase chain reaction (RT-qPCR) were used to detect the expressions of stemness markers and PD-L1. The biological functions of the LCSLC were tested by cell function assays, to confirm that the LCSLC has the characteristics of tumor stem cells. LCSLC was treated with cell signaling pathway inhibitors to identify relevant upstream signaling pathways mediating PD-L1 expression changes. The expression of PD-L1 in LCSLC was down regulated by small interfering RNA (siRNA), the expression of stem cell markers, tumor biological functions of LCSLC, and the changes of cell signaling pathways were detected. Results: Compared with HepG2 cells, the expression rate of CD133 in LCSLC was upregulated [(92.78±6.91)% and (1.40±1.77)%, P<0.001], the expressions of CD133, Nanog, Oct4A and Snail in LCSLC were also higher than those in HepG2 cells (P<0.05), the number of sphere-formating cells increased on day 7 [(395.30±54.05) and (124.70±19.30), P=0.001], cell migration rate increased [(35.41±6.78)% and (10.89±4.34)%, P=0.006], the number of transmembrane cells increased [(75.77±10.85) and (20.00±7.94), P=0.002], the number of cloned cells increased [(120.00±29.51) and (62.67±16.77), P=0.043]. Cell cycle experiments showed that LCSLC had significantly more cells in the G(0)/G(1) phase than those in HepG2 [(54.89±3.27) and (32.36±1.50), P<0.001]. The tumor formation experiment of mice showed that the weight of transplanted tumor in LCSLC group was (1.32±0.17)g, the volume is (1 779.0±200.2) mm(3), were higher than those of HepG2 cell [(0.31±0.06)g and (645.6±154.9)mm(3), P<0.001]. The expression level of PD-L1 protein in LCSLC was 1.88±0.52 and mRNA expression level was 2.53±0.62, both of which were higher than those of HepG2 cells (P<0.05). The expression levels of phosphorylation signal transduction and transcription activation factor 3 (p-STAT3) and p-Akt in LCSLC were higher than those in HepG2 cells (P<0.05). After the expression of p-STAT3 and p-Akt was down-regulated by inhibitor treatment, the expression of PD-L1 was also down-regulated (P<0.05). In contrast, the expression level of phosphorylated extracellular signal-regulated protein kinase 1/2 (p-ERK1/2) in LCSLC was lower than that in HepG2 cells (P<0.01), there was no significant change in PD-L1 expression after down-regulated by inhibitor treatment (P>0.05). After the expression of PD-L1 was knockdown by siRNA, the expressions of CD133, Nanog, Oct4A and Snail in LCSLC were decreased compared with those of siRNA-negative control (NC) group (P<0.05). The number of sphere-formating cells decreased [(45.33±12.01) and (282.00±29.21), P<0.001], the cell migration rate was lower than that in siRNA-NC group [(20.86±2.74)% and (46.73±15.43)%, P=0.046], the number of transmembrane cells decreased [(39.67±1.53) and (102.70±11.59), P=0.001], the number of cloned cells decreased [(57.67±14.57) and (120.70±15.04), P=0.007], the number of cells in G(0)/G(1) phase decreased [(37.68±2.51) and (57.27±0.92), P<0.001], the number of cells in S phase was more than that in siRNA-NC group [(30.78±0.52) and (15.52±0.83), P<0.001]. Tumor formation in mice showed that the tumor weight of shRNA-PD-L1 group was (0.47±0.12)g, the volume is (761.3±221.4)mm(3), were lower than those of shRNA-NC group [(1.57±0.45)g and (1 829.0±218.3)mm(3), P<0.001]. Meanwhile, the expression levels of p-STAT3 and p-Akt in siRNA-PD-L1 group were decreased (P<0.05), while the expression levels of p-ERK1/2 and β-catenin did not change significantly (P>0.05). Conclusion: Elevated PD-L1 expression in CD133(+) LCSLC is crucial to maintain stemness and promotes the tumor biological function of LCSLC.

The effect of BMI and age on the outcomes of microsurgical vasoepididymostomy: a retrospective analysis of 181 patients operated by a single surgeon / 亚洲男科学杂志(英文版)

To design a treatment plan for patients with epididymal obstruction, we explored the potential impact of factors such as body mass index (BMI) and age on the surgical outcomes of vasoepididymostomy (VE). In this retrospective study, 181 patients diagnosed with obstructive azoospermia (OA) due to epididymal obstruction between September 2014 and September 2017 were reviewed. All patients underwent single-armed microsurgical intussusception VEs with longitudinal two-suture placement performed by a single surgeon (KH) in a single hospital (Peking University Third Hospital, Beijing, China). Six factors that could possibly influence the patency rates were analyzed, including BMI, age, mode of anastomosis, site of anastomosis, and sperm motility and quantity in the intraoperative epididymal fluid. Single-factor outcome analysis was performed via Chi-square test and multivariable analysis was performed using logistic regression. A total of 159 (87.8%, 159/181) patients were followed up. The follow-up time (mean ± standard deviation [s.d.]) was 27.7 ± 9.3 months, ranging from 12 months to 48 months. The overall patency rate was 73.0% (116/159). The multivariable analysis revealed that BMI and age significantly influenced the patency rate (P = 0.008 and 0.028, respectively). Younger age (≤28 years; odds ratio [OR] = 3.531, 95% confidence interval [95% CI]: 1.397-8.924) and lower BMI score (<26.0 kg m-2; OR = 2.352, 95% CI: 1.095-5.054) appeared to be associated with a higher patency rate. BMI and age were independent factors affecting the outcomes of microsurgical VEs depending on surgical expertise and the use of advanced technology.

Prenatal diagnosis and genetic analysis of a special case with complex structural rearrangements of chromosome 8 / 中华医学遗传学杂志

OBJECTIVE@#To present on a prenatally diagnosed case with complex structural rearrangements of chromosome 8.@*METHODS@#Chromosome karyotyping, chromosomal microarray analysis (CMA) and fluorescence in situ hybridization (FISH) were carried out for a fetus with increased nuchal thickness.@*RESULTS@#The karyotype of the amniotic fluid sample showed extra materials on 8p. FISH revealed a centromeric signal at the terminal of 8p with absence of telomeric signal. CMA revealed partial deletion of 8p23.3 [(208049_2256732)×1], partial duplication of 8p23.3p23.2 [(2259519_3016818)×3], and partial duplication of 8q [8q11.1q12.2(45951900_60989083)×3].@*CONCLUSION@#The complex structural rearrangements of chromosome 8 in this case has differed from the commonly seen inv dup del(8p).

Effect of Wine Processing on Odour Formation of Polygonatum cyrtonema Rhizoma by GC-MS / 中国实验方剂学杂志

ObjectiveBy exploring the volatile components， polysaccharide composition and changes in the contents of five carbohydrate components of Polygonatum cyrtonema rhizoma before and after processing， and then the effect of yellow rice wine on the odour formation of P. cyrtonema rhizoma was investigated. MethodThe volatile components of P. cyrtonema rhizoma before and after processing were detected by headspace gas chromatography-mass spectrometry（HS-GC-MS）， and sample data were subjected to principal component analysis（PCA） and orthogonal partial least squares-discriminant analysis（OPLS-DA） using SIMCA 14.1， then the differences between these components of P. cyrtonema rhizoma before and after processing were screened according to the principle of variable importance in the projection（VIP） value>1. Crude carbohydrate components in raw and wine-processed P. cyrtonema rhizoma were subjected to oxime and silylation， the carbohydrate components were analyzed by gas chromatography-mass spectrometry（GC-MS/MS）， and the relative contents of various components were calculated by peak area normalization， then quantitative analysis of four carbohydrate components was also carried out. ResultA total of 23 volatile components were identified from the raw products and the wine-processed products， including 15 components in raw products and 20 components in wine-processed products. Among them， 2-methylbutyraldehyde and isovaleraldehyde had a sweet odor and their contents increased after processing， but the contents of hexanal and caproic acid decreased， new components such as 2-acetylfuran and 5-methylfuranal were produced after processing. PCA and OPLS-DA results showed that there were significant differences between raw products and the wine-processed products， a total of 13 differential compounds were screened out， of which 7 showed an upward trend in relative content and 6 showed a downward trend. A total of 7 carbohydrate components， including 5 monosaccharides and 2 disaccharides， were identified in raw products and the wine-processed products. The results of determination showed that the contents of fructose， glucose， mannose and sucrose in P. cyrtonema rhizoma increased after wine-processing， and their increases were 4.54， 1.51， 2.93， 3.66 times， respectively. ConclusionAfter processing， the increase of aromatic flavor of P. cyrtonema rhizoma may be related to the increase of the contents of aldehydes such as 2-methylbutyraldehyde and isovaleraldehyde， while the decrease of raw flavor may be related to the decrease of the contents of volatile components such as hexanal and hexanoic acid， the increase of sweet flavor may be related to the increase of the contents of monosaccharides and oligosaccharides such as fructose and sucrose.

Effect and mechanism of gerbeloid J from Gerbera piloselloides (L.) Cass. on cycle and apoptosis of breast cancer cells / 药学学报

Breast cancer has become the most prevalent malignant tumor among women, putting the health of women at serious risk. Screening for lead compounds in the active ingredients of plant that are effective and less toxic continues to be an important strategy for treating breast cancer. Gerbeloid J, a coumarin isolated from Gerbera piloselloides (L.) Cass., showed significant anti-cancer activity. But there is no report on the effect and mechanism of gerbeloid J on cycle and apoptosis of breast cancer. By using the CCK-8, clone formation, and PI staining assays, the effects of gerbeloid J on the proliferation of MCF-7 and MDA-MB-231 cells were assessed in this study. The effects of gerbeloid J on the apoptosis and mitochondrial function of MCF-7 and MDA-MB-231 cells were assessed using DAPI, Annexin V/TO-PRO-3, Rhod-2 AM, TMRM, DCFDA staining assays, and Western blot. The results demonstrated that gerbeloid J regulated the P21/CDC25C/CDK-1/cyclin B1 pathway and arrested the cell cycle at G2/M phase to suppressed the proliferation of MCF-7 and MDA-MB-231 cells. Additionally, gerbeloid J induced apoptosis through the stimulation of mitochondrial calcium excess, reduction of mitochondrial membrane potential, and promotion of ROS generation, and its mechanism was related to the activation of mitochondrial apoptotic pathway. In conclusion, by regulating the P21/CDC25C/CDK-1/cyclin B1 pathway and activating the mitochondrial apoptosis pathway, gerbeloid J could cause breast cancer cell cycle arrest and apoptosis, which might offer a promising candidate for the creation of new drugs against breast cancer.

A new germacrene-type sesquiterpenoid from Elephantopus tomentosus L / 药学学报

Fifteen compounds were isolated from the 95% ethanol extract of the whole plant of Elephantopus tomentosus L. by silica gel column chromatography, Sephadex LH-20 column chromatography, MCI column chromatography and semi-preparative HPLC methods. Their structures were identified on the basis of physicochemical properties, and spectral data (UV, IR, NMR, MS and CD) analysis as tomenlephanlide A (1), molephantinin (2), molephantin (3), 8-O-methacryloylelephanpane (4), apigenin (5), tricin (6), 2-phenyl acetamide (7), 3,4-dihydroxybenzoic acid methyl ester (8), caffeic acid methyl ester (9), caffeic acid ethyl ester (10), (+)-(4S)-(2E)-4-hydroxy-2-nonenoic acid (11), E-4-hydroxyhex-2-enoic acid (12), 1H-indole-3-carboxylic acid (13), 1H-indole-3-carbaldehyde (14) and isohematinic acid (15). Among them, compound 1 is a new germacrene-type sesquiterpenoid, 5-15 were obtained from E. tomentosus L. for the first time. It was the first time the absolute configuration of compound 2 was reported. Compound 1 showed weak cytotoxicity against gastric cancer cells (SGC-7901).