Objective To investigate the mechanism of Yiqi Huoxue Huazhuo Jiedu Prescription in regulating the endoplasmic reticulum stress PERK/ATF4 signaling pathway to improve cerebral ischemia reperfusion injury in rats.Methods A total of 48 male SD rats were randomly divided into sham-operation group,model group,TCM group and edaravone group,with 12 rats in each group.Cerebral ischemia reperfusion injury rat model was prepared using middle cerebral artery occlusion method,and administration 24 hours after modeling.The edaravone group was given intraperitoneal injection of 1.4 mg/mL edaravone injection,TCM group was given 55 g/(kg·d)of Yiqi Huoxue Huazhuo Jiedu Prescription for gavage,while the sham-operation group and model group were given equal volumes of normal saline for gavage,twice a day for 3 consecutive days.The neurological deficit scores of the rats in each group were observed,TTC staining was used to detect the volume of cerebral infarction,HE staining was used to observe the morphology of brain tissue in the ischemia-reperfusion area,immunohistochemistry staining was used to detect the positive expressions of glucose regulated protein 78(GRP78),protein kinase R-like endoplasmic reticulum kinase(PERK)and transcription activator factor(ATF)4 in the ischemia-reperfusion area brain tissue,RT-PCR was used to detect the mRNA expressions of GRP78,PERK and ATF4 in the ischemia-reperfusion area brain tissue,Western blot was used to detect the protein expressions of GRP78,PERK and ATF4 in the ischemia-reperfusion area brain tissue.Results Compared with the sham-operation group,the neurological deficit score of the model group rats increased,the volume of cerebral infarction increased,the number of neurons in the ischemia-reperfusion area decreased,the arrangement was loose,and the nuclei were condensed,the mRNA and protein expressions of GRP78,PERK and ATF4 increased,with statistical significance(P<0.05).Compared with the model group,the neurological deficit score of TCM group and edaravone group decreased,the cerebral infarction volume decreased,the number and arrangement of neurons of the brain tissue in the ischemia reperfusion area increased,and nuclear condensation decreased in rats,the mRNA and protein expressions of GRP78,PERK and ATF4 were all reduced,with statistical significance(P<0.05).There was no statistical significance in various indicators between TCM group and the edaravone group(P>0.05).Conclusion Yiqi Huoxue Huazhuo Jiedu Prescription can improve cerebral ischemia reperfusion injury,and its mechanism may be related to down-regulating the expression of PERK/ATF4 signaling pathway and alleviating endoplasmic reticulum stress.

Objective To investigate the mechanism of Yiqi Huoxue Huazhuo Jiedu Prescription in regulating the endoplasmic reticulum stress PERK/ATF4 signaling pathway to improve cerebral ischemia reperfusion injury in rats.Methods A total of 48 male SD rats were randomly divided into sham-operation group,model group,TCM group and edaravone group,with 12 rats in each group.Cerebral ischemia reperfusion injury rat model was prepared using middle cerebral artery occlusion method,and administration 24 hours after modeling.The edaravone group was given intraperitoneal injection of 1.4 mg/mL edaravone injection,TCM group was given 55 g/(kg·d)of Yiqi Huoxue Huazhuo Jiedu Prescription for gavage,while the sham-operation group and model group were given equal volumes of normal saline for gavage,twice a day for 3 consecutive days.The neurological deficit scores of the rats in each group were observed,TTC staining was used to detect the volume of cerebral infarction,HE staining was used to observe the morphology of brain tissue in the ischemia-reperfusion area,immunohistochemistry staining was used to detect the positive expressions of glucose regulated protein 78(GRP78),protein kinase R-like endoplasmic reticulum kinase(PERK)and transcription activator factor(ATF)4 in the ischemia-reperfusion area brain tissue,RT-PCR was used to detect the mRNA expressions of GRP78,PERK and ATF4 in the ischemia-reperfusion area brain tissue,Western blot was used to detect the protein expressions of GRP78,PERK and ATF4 in the ischemia-reperfusion area brain tissue.Results Compared with the sham-operation group,the neurological deficit score of the model group rats increased,the volume of cerebral infarction increased,the number of neurons in the ischemia-reperfusion area decreased,the arrangement was loose,and the nuclei were condensed,the mRNA and protein expressions of GRP78,PERK and ATF4 increased,with statistical significance(P<0.05).Compared with the model group,the neurological deficit score of TCM group and edaravone group decreased,the cerebral infarction volume decreased,the number and arrangement of neurons of the brain tissue in the ischemia reperfusion area increased,and nuclear condensation decreased in rats,the mRNA and protein expressions of GRP78,PERK and ATF4 were all reduced,with statistical significance(P<0.05).There was no statistical significance in various indicators between TCM group and the edaravone group(P>0.05).Conclusion Yiqi Huoxue Huazhuo Jiedu Prescription can improve cerebral ischemia reperfusion injury,and its mechanism may be related to down-regulating the expression of PERK/ATF4 signaling pathway and alleviating endoplasmic reticulum stress.

Background::Although some well-established oncogenes are involved in cancer initiation and progression such as prostate cancer (PCa), the long tail of cancer genes remains to be defined. Goosecoid ( GSC) has been implicated in cancer development. However, the comprehensive biological role of GSC in pan-cancer, specifically in PCa, remains unexplored. The aim of this study was to investigate the role of GSC in PCa development. Methods::We performed a systematic bioinformatics exploration of GSC using datasets from The Cancer Genome Atlas, Genotype-Tissue Expression, Gene Expression Omnibus, German Cancer Research Center, and our in-house cohorts. First, we evaluated the expression of GSC and its association with patient prognosis, and identified GSC-relevant genetic alterations in cancers. Further, we focused on the clinical characterization and prognostic analysis of GSC in PCa. To understand the transcriptional regulation of GSC by E2F transcription factor 1 ( E2F1), we performed chromatin immunoprecipitation quantitative polymerase chain reaction (qPCR). Functional experiments were conducted to validate the effect of GSC on the tumor cellular phenotype and sensitivity to trametinib. Results::GSC expression was elevated in various tumors and significantly correlated with patient prognosis. The alterations of GSC contribute to the progression of various tumors especially in PCa. Patients with PCa and high GSC expression exhibited worse progression-free survival and biochemical recurrence outcomes. Further, GSC upregulation in patients with PCa was mostly accompanied with higher Gleason score, advanced tumor stage, lymph node metastasis, and elevated prostate-specific antigen (PSA) levels. Mechanistically, the transcription factor, E2F1, stimulates GSC by binding to its promoter region. Detailed experiments further demonstrated that GSC acted as an oncogene and influenced the response of PCa cells to trametinib treatment. Conclusions::GSC was highly overexpressed and strongly correlated with patient prognosis in PCa. We found that GSC, regulated by E2F1, acted as an oncogene and impeded the therapeutic efficacy of trametinib in PCa.

Data analysis models may assist the transmission of traditional Chinese medicine （TCM） experience and clinical diagnosis and treatment， and the possibility of constructing a “data-knowledge” dual-drive model was explored by taking gastric precancerous state as an example. Data-driven is to make clinical decisions around data analysis， and its syndrome-differentiation decision-making research relies on hidden structural models and partially observable Markov decision-making processes to identify the etiology of diseases， syndrome elements， evolution of pathogenesis， and syndrome differentiation protocols； knowledge-driven is to make use of data and information to promote decision-making and action processes， and its syndrome-differentiation decision-making research relies on convolutional neural networks to improve the accuracy of local disease identification and syndrome differentiation. The “data-knowledge” dual-driven model can make up for the shortcomings of single-drive numerical simulation accuracy， and achieve a balance between local disease identification and macroscopic syndrome differentiation. On the basis of previous research， we explored the construction method of diagnostic assisted decision-making platform for gastric precancerous state， and believed that the diagnostic and decision-making ability of doctors can be extended through the assistance of machines and algorithms. Meanwhile， the related research methods were integrated and the core features of gastric precancerous state based on TCM syndrome differentiation and endoscopic pathology diagnosis and prediction were obtained， and the elements of endoscopic pathology recognition based on TCM syndrome differentiation were explored， so as to provide ideas for the in-depth research and innovative application of cutting-edge data analysis technology in the field of intelligent TCM syndrome differentiation.

Objective:To investigate the clinical characteristics, diagnosis and treatment of dermatomyositis with kidney neoplasm.Methods:The data of two patients with dermatomyositis complicated with kidney neoplasm in Tongji Hospital from January to February 2022 were retrospectively analyzed. The first case was a 55-year-old female, who was admitted with the chief complaints of recurrent erythema of upper extremities for 2 months and facial erythema for 1 month. Physical examination: erythema can be seen on upper limbs and face, no tenderness or percussion pain in kidney area. Myositis enzyme profile test showed that anti-Mi-2 antibody and anti-SSA /Ro-52 antibody were positive. Contrast CT showed nodular uneven enhancement in the right kidney with a size of 50 mm×41 mm. The second case was a 58-year-old female, who was admitted with the chief complaints of kidney occupying for a month. Physical examination: flaky erythema on face, no tenderness or percussion pain in kidney area. Myositis enzyme profile test showed that anti-Ro-52 antibody and anti-MDA5 antibody were positive. Contrast CT showed a significantly uneven enhanced mass with a size of about 50 mm×41 mm on left kidney. Both patients were diagnosed with kidney neoplasm before surgery and underwent laparoscopic partial nephrectomy in Tongji Hospital.Results:Both patients received regular oral prednisone after surgery. The pathological presentation of case 1 was papillary renal cell carcinoma, the facial erythema subsided 1 month after surgery, and there was no tumor recurrence for 13 months. The pathological presentation of case 2 was clear cell renal cell carcinoma, facial erythema subsided 2 weeks after surgery, and there was no tumor recurrence for 12 months.Conclusions:The diagnosis of dermatomyositis should be combined with clinical manifestations and laboratory examination, and the possibility of malignant tumor should be excluded due to the high likelihood of concomitant malignancy. For patients with dermatomyositis with kidney neoplasm, the main treatment is still surgery, and supplemented with glucocorticoid therapy.

The 2023 American Society of Clinical Oncology Genitourinary Cancers Symposium unveiled numerous research advances which provide meaningful insights into the selection of treatment regimens of prostate cancer. Precision multi-treatment based on patients’ characteristics has become the predominant approach, including the use of a three-drug combination therapy for metastatic hormone-sensitive prostate cancer, and poly adenosine diphosphate ribose polymerase inhibitor therapy for metastatic castration-resistant prostate cancer. Nuclear medicine therapy and radiotherapy are also receiving significant attention. Integrated nuclear medicine diagnosis and therapy show immense potential for non-metastatic castration-resistant prostate cancer. Additionally, for localized prostate cancer, stereotactic body radiotherapy is a preferred alternative to surgery. This article sheds light on several key studies presented at the conference, focuses on prostate cancer treatment at different stages, and intends to enhance the therapeutic outcome for prostate cancer patients.

The typical hallmark of tumor evolution is metabolic dysregulation. In addition to secreting immunoregulatory metabolites, tumor cells and various immune cells display different metabolic pathways and plasticity. Harnessing the metabolic differences to reduce the tumor and immunosuppressive cells while enhancing the activity of positive immunoregulatory cells is a promising strategy. We develop a nanoplatform (CLCeMOF) based on cerium metal-organic framework (CeMOF) by lactate oxidase (LOX) modification and glutaminase inhibitor (CB839) loading. The cascade catalytic reactions induced by CLCeMOF generate reactive oxygen species "storm" to elicit immune responses. Meanwhile, LOX-mediated metabolite lactate exhaustion relieves the immunosuppressive tumor microenvironment, preparing the ground for intracellular regulation. Most noticeably, the immunometabolic checkpoint blockade therapy, as a result of glutamine antagonism, is exploited for overall cell mobilization. It is found that CLCeMOF inhibited glutamine metabolism-dependent cells (tumor cells, immunosuppressive cells, etc.), increased infiltration of dendritic cells, and especially reprogrammed CD8⁺ T lymphocytes with considerable metabolic flexibility toward a highly activated, long-lived, and memory-like phenotype. Such an idea intervenes both metabolite (lactate) and cellular metabolic pathway, which essentially alters overall cell fates toward the desired situation. Collectively, the metabolic intervention strategy is bound to break the evolutionary adaptability of tumors for reinforced immunotherapy.

Objective Taking 41 kinds of Chinese herbal medicines commonly used in Meizhou Hakka as the research object,their inhibitory activities against α-glucosidase and α-amylase were screened and the enzyme inhibition types of the species with the strongest activities were explored.Methods The inhibitory activities of 41 commonly used Hakka herbs in Meizhou against α-glucosidase and α-amylase were evaluated by the p-Nitrophenyl a-D-mannopyranoside(pNPG)method and the 3,5-Dinitrosalicylic acid(DNS)method,using the inhibitory rate of half(IC50)as an index.The inhibitory activity of 95%ethanol extracts of 41 Chinese herbal medicines commonly used in Meizhou Hakka on α-glucosidase and α-amylase were analysed.The enzymatic kinetics method and Lineweaver-Burk curve were used to analyze the inhibitory type of the most active species.Results The results showed that 40 Chinese herbal medicines commonly used in Meizhou Hakka had α-glucosidase inhibitory activity,and 23 medicines had α-amylase inhibitory activity,among which Psychotria asiatica Wall.showed the strongest inhibitory activity with the IC50 values aganist α-glucosidase and α-amylase of 0.17±0.001 mg·mL-1 and 0.09±0.001 mg·mL-1,respectively.The inhibition types were reversible competitive inhibition and reversible non-competitive inhibition,respectively.Conclusion The Psychotria asiatica Wall.Chinese herbal medicines commonly used in Meizhou Hakka has significant inhibitory effect on the activity of glucose metabolism enzymes,which has potential value for further research and development on the prevention and treatment of diabetes mellitus.

Objective To summarize the magnetic resonance imaging (MRI) features of the persistcnt perineal sinus (PPS).Methods The retrospective and descriptive study was conducted.The clinical data of 7 patients with PPS who were admitted to the Nanjing University of Traditional Chinese Medicine between July 2010 and January 2017 were collected.Patients received horizontal,anteroposterior axes and coronal scanning of MRI after abdominoperineal resection (APR) of rectal cancer.Two physicians read collectively films and then achieved consistent results if there was a disputed result.Observation indicators:(1) MRI features;(2) treatment and follow-up situations.Patients underwent resection of PPS according to results of MRI examination,and then regular pathological examination.Follow-up using telephone interview was performed to detect sinus recurrence and reoperation up to April 2017.Results (1) MRI features:① Lesion location:lesions of PPS in 7 patients were located at the presacral areas,top side was up to the third sacral plane,and lower side extended down to the pubic area.② Morphology and signal:sinus tract of 7 patients showed irregular flaky and tubular abnormal signals;fibrotic sinus tract wall showed low signals in T1 weighted imaging (T1WI) and T2WI;contents of sinus tract in 7 patients showed low signal in T1WI and high signals in T2WI and T2WI-fat suppression (T2WI-FS).Of 7 patients,uniform signal and mixed signal were respectively detected in 2 and 5 patients.③ Branches and cystic spaces:1 patient had a branch at the tip of the coccyx,extending to the rear of the sacral vertebra.The top of sinus tract in 4 patients enlarged to form a cavity.④ Signs of infection:signs of infection in 3 patients included blurred and exuded fat gaps around the sinus tract,unclear and partially adhesion with pelvic organ;the pelvic floor muscles in 1 patient were thickened and swollen,with a high signal in T2WI-FS;flaky fluid shadows in 2 patients were seen in the posterior sinus,with a high signal in T2WI-FS,showing a tissue edema of anterior sacrum.⑤ Enhancement features:result of MRI examination of 1 patient showed mild and heterogeneous enhancement of sinus.(2) Treatment and follow-up situations:among 7 patients undergoing sinus resection,2 received curettage of superior sinus due to high location,and 5 received successfully operation.All patients underwent postoperatively regular antibiotic therapy.The healing time was 14-78 days,with an average time of 42 days.The postoperative pathological examination showed different degrees of inflammatory cell infiltration.Seven patients were followed up for 2-74 months,with an average time of 40 months.Of 7 patients,sinus in 6 patients was healed,1 had recurrence of sinus and didn't receive therapy.Seven patients didn't undergo debridement or transposition of skin flap again.Conclusion The MRI imaging features of PPS includes flaky and tubular abnormal signal in the the anterior sacrum,low signal in T1WI,high signals in T2WI and T2WI-FS,and the enhanced scanning of sinus duet shows mild and heterogeneous enhancement.

BACKGROUND:As a noticeable tissue engineering material of polyhy droxyalka noates family, poly (3-hydroxybutyrate-co-4-hydroxybutyrate)(P3HB4HB) exhibitsgood biocompatibility, adhesion and mechanicalproperties, presenting aextensive application future in tissue-engineered research.
OBJECTIVE:To investigate the biocompat ibilityin vitroand ectopic osteogenic differentiationin vivoof P3HB4HB and human bone marrow mesenchymal stem cels.
METHODS:Passage 5human bone marrow mesenchymal stem cels transplanted ontothe three-dimensional P3HB4HB scaffoldwereincubated with osteogenic induction medium (test group)or with no osteogenic induction(control group), respectively. After 5-day incubation, thecelgrowth was assessed by acridine orange staining and scanning electron microscopy; after14-day incubation, both kinds of cel-scaffold composites were subcutaneously implanted into the nude mice. At 16 weeks after implantation, the cel-scaffold composites were removed to observeectopic osteogenic differentiationin vivousing hematoxylin-eosin staining, von Kossa staining and colagen type I immunohistochemical staining.
RESULTS AND CONCLUSION:Acridine orange staining showed that cels adhered wel on the surface of the scaffold;under thescanning electron microscope, induced celsgrew wel on the P3HB4HB scaffold and produced abundant extracelular matrixes. In addition, at 16 weeks after implantation, there were osteoidtissues in the test group, positive for von Kossa staining as wel as colagen type I immunohistochemical staining;furthermore, hematoxylin-eosin staining showednumerous osteoblasts and bone lacunas. In contrast, no bone tissues appeared in the control group. To conclude, P3HB4HB is a suitable material for bone tissue engineering.