Objective:To investigate the effects of Shenghui Yizhi Decoction on learning and memory ability of SAMP8 mice; To explore its mechanism.Methods:Totally 24 male SAMP8 mice were randomly divided into model group, donepezil hydrochloride group (1 mg/kg) and Shenghui Yizhi Decoction group (15.6 g/kg), with 8 mice in each group, and eight anti rapid aging mice (SAMR1) of the same age and strain were set as the control group. The mice in each group were given corresponding medication or the same volume of distilled water for 90 days. After administration, Morris water maze was used to detect the learning and memory ability and space exploration ability of mice. Immunohistochemistry was used to detect expression of β Amyloid protein 1-42 (Aβ 1-42) in hippocampal. ELISA was used to detect the levels of interleukin-1β (IL-1β), interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α). Real time PCR was used to detect expressions of NOD-like receptor thermal protein domain associated protein 3 (NLRP3), cysteine protease-1 (Caspase-1), and IL-1β mRNA. Western Blot was used to detect expression of NLRP3, Caspase-1and IL-1β protein. Results:Compared with model group, the spatial exploration ability and memory ability of mice in Shenghui Yizhi Decoction group and donepezil hydrochloride group were improved ( P<0.05, P<0.01), the expression of Aβ 1-42 in hippocampus decreased ( P<0.05, P<0.01), the contents of IL-1β, IL-6 and TNF-α decreased ( P<0.05, P<0.01), and the mRNA and protein expressions of NLRP3, Caspase-1 and IL-1β decreased ( P<0.05, P<0.01). Conclusion:Shenghui Yizhi Decoction can effectively improve the learning and memory ability of SAMP8 mice, and its mechanism may be related to inhibiting the activation of inflammasome and neuroinflammatory response by regulating the NLRP3/ Caspase-1/ IL-1β signaling pathway.

Concurrent chemoradiotherapy (CCRT) refers to the simultaneous treatment of chemotherapy and radiotherapy, and the effect of radiotherapy is enhanced with low-dose chemotherapy, which can reduce tumor recurrence and metastasis and improve clinical prognosis of patients. At present, the main factors for the increase of radiosensitivity of concurrent chemotherapy is that concurrent chemotherapy prevents the repair of tumor cells, and chemotherapy and radiotherapy act on different cell cycles and have synergistic effects. However, even for patients with locally advanced cervical cancer (LACC) who have undergone CCRT, the 5-year survival rate is only 60%, which is still not ideal. In order to improve the efficacy, researchers have conducted a series of exploratory studies, which consist of the combination of targeted drugs and immunodrugs, and neoadjuvant regimens before CCRT, etc. Although targeted or immunologic drugs are effective treatment of LACC, in view of the lack of large-scale evidence-based medical evidence, multi-center prospective and randomized phase III clinical trials and high-level articles are needed to improve the level of evidence-based medicine. This consensus summarizes several key evidence-based medical studies published recently, especially the clinical research progress in targeted and immunological therapies, providing reference for domestic peers.

Mulberry (Morus alba L.) leaf is a well-established traditional Chinese botanical and culinary resource. It has found widespread application in the management of diabetes. The bioactive constituents of mulberry leaf, specifically mulberry leaf flavonoids (MLFs), exhibit pronounced potential in the amelioration of type 2 diabetes (T2D). This potential is attributed to their ability to safeguard pancreatic β cells, enhance insulin resistance, and inhibit α-glucosidase activity. Our antecedent research findings underscore the substantial therapeutic efficacy of MLFs in treating T2D. However, the precise mechanistic underpinnings of MLF's anti-T2D effects remain the subject of inquiry. Activation of brown/beige adipocytes is a novel and promising strategy for T2D treatment. In the present study, our primary objective was to elucidate the impact of MLFs on adipose tissue browning in db/db mice and 3T3-L1 cells and elucidate its underlying mechanism. The results manifested that MLFs reduced body weight and food intake, alleviated hepatic steatosis, improved insulin sensitivity, and increased lipolysis and thermogenesis in db/db mice. Moreover, MLFs activated brown adipose tissue (BAT) and induced the browning of inguinal white adipose tissue (IWAT) and 3T3-L1 adipocytes by increasing the expressions of brown adipocyte marker genes and proteins such as uncoupling protein 1 (UCP1) and beige adipocyte marker genes such as transmembrane protein 26 (Tmem26), thereby promoting mitochondrial biogenesis. Mechanistically, MLFs facilitated the activation of BAT and the induction of WAT browning to ameliorate T2D primarily through the activation of AMP-activated protein kinase (AMPK)/sirtuin 1 (SIRT1)/peroxisome proliferator-activated receptor-gamma coactivator 1α (PGC-1α) signaling pathway. These findings highlight the unique capacity of MLF to counteract T2D by enhancing BAT activation and inducing browning of IWAT, thereby ameliorating glucose and lipid metabolism disorders. As such, MLFs emerge as a prospective and innovative browning agent for the treatment of T2D.
Mice ; Animals ; Adipose Tissue, Brown ; Sirtuin 1/pharmacology* ; Diabetes Mellitus, Type 2/metabolism* ; AMP-Activated Protein Kinases/metabolism* ; Morus/metabolism* ; Flavonoids/metabolism* ; Prospective Studies ; Signal Transduction ; Adipose Tissue, White ; Plant Leaves ; Uncoupling Protein 1/metabolism* ; Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha/metabolism*

Objective:To compare the dosimetry and efficacy of intracavitary brachytherapy (ICBT) and intracavitary/interstitial brachytherapy (IC+ ISBT) based on CT image guidance in the treatment of stage Ⅲ B cervical cancer. Methods:Clinical data of 93 patients with stage Ⅲ B cervical cancer treated in Department of Radiotherapy of Jilin Cancer Hospital from June 2014 to February 2017 were analyzed retrospectively. According to the results of Gynecological examination and pelvic MRI before brachytherapy, confirming the size of residual tumor and the degree of parauterine infiltration, all patients were divided into the ICBT and IC+ ISBT groups. The D 90%, D 100%, V 100% and D 2cm 3 of bladder and rectum were compared, and the short-term and long-term efficacy was observed between two groups. Results:The median follow-up time was 60 months. The 5-year local control rate, distant metastasis-free survival rate and overall survival rate of all patients were 83%, 71% and 68%, respectively. Compared with the ICBT group, HR-CTV D 90% in the IC+ ISBT group was all more than 85 Gy, while there was no significant difference between two groups ( P=0.188). The D 2cm 3 of bladder and rectum in the IC+ ISBT group was significantly decreased by 7 Gy and 8 Gy (both P<0.01), and the distant metastasis-free survival rate was significantly improved ( P=0.009). The 5-year local control rate in the HR-CTV volume>60 cm 3 in the IC+ ISBT group was significantly higher than that in the IC group ( P=0.029). Conclusion:For patients with Ⅲ B cervical cancer, IC+ ISBT can not only ensure target coverage, but also significantly reduce the incidence of distant metastasis and the dose of organs at risk, and significantly improve the local control rate of large tumors.

Objective:To investigate the changes of non-specific and HBV core antigen (HBcAg)-specific Th9 cells, and intereleukin-9 (IL-9) in HBV-infected patients, and to assess the influence of Th9 cells on CD8 + T cell function. Methods:Twelve patients with acute hepatitis B (AHB) and 58 with chronic hepatitis B (CHB), who were hospitalized in the First Affiliated Hospital of Xinxiang Medical University between January 2018 and January 2019, were enrolled in this study. Twenty healthy subjects negative for HBsAg were selected as controls. Peripheral blood mononuclear cells (PBMCs) and plasma samples were isolated. Non-specific Th9 cells (CD3 + CD4 + IL-9 + ) and HBcAg-specific Th9 cells were analyzed by flow cytometry. Plasma IL-9 level was measured by enzyme linked immunosorbent assay. CHB patients received tenofovir disoproxil fumarate (TDF) antiviral therapy. The changes of non-specific Th9 cells, HBcAg-specific Th9 cells and plasma IL-9 level were assessed 48 weeks after TDF therapy. CD4 + CCR4 -CCR6 -CXCR3 -(Th9) cells and CD8 + T cells were isolated from 12 HLA-A2 restricted CHB patients and co-cultured with HepG2.2.15 cells with the presence of anti-IL-9 neutralizing antibody. The percentage of dead HepG2.2.15 cells and the levels of IFN-γ and TNF-α were detected. Student′s t test, one-way analysis of variance or SNK- q test was used for statistical comparison between groups. Results:There were no significant differences in non-specific Th9 cells or plasma IL-9 level among AHB patients, CHB patients and healthy controls ( P>0.05). HBcAg-specific Th9 cells was down-regulated in CHB patients when compared with AHB patients [(2.49±0.61)% vs (3.19±0.62)%, P<0.001]. The percentage of HBcAg-specific Th9 cells was negatively correlated with HBV DNA ( r=-0.385, P=0.003), but not correlated with ALT ( P>0.05) in CHB patients. TDF therapy for 48 weeks remarkably elevated the HBcAg-specific Th9 cells [(2.94±0.48)%, P<0.001], however, did not affect non-specific Th9 cells or plasma IL-9 level ( P>0.05) in CHB patients. The cytotoxicity of HBcAg-specific Th9 cells was low in CHB patients. However, HBcAg-specific Th9 cells could induce enhanced cytotoxicity of CD8 + T cells to HepG2.2.15 cells, which manifested as increased percentage of dead HepG2.2.15 cells and higher levels of IFN-γ and TNF-α. Anti-IL-9 neutralizing antibody reduced the enhancement of CD8 + T cell cytotoxicity by HBcAg-specific Th9 cells ( P<0.001). Conclusions:Chronic HBV infection might suppress the level and function of HBcAg-specific Th9 cells, resulting in persistent infection.

The main treatment options for cervical cancer include surgery and/or radiotherapy combined with chemotherapy. Radiotherapy consists of external beam radiotherapy and brachytherapy (BT). BT contains high-dose-rate (HDR-BT) and low-dose-rate brachytherapy (LDR-BT). The prognosis of cervical cancer is relatively good. However, some patients experience substantial treatment failures, such as intra-pelvic and/or extra-pelvic recurrences. Recurrent cervical cancer (RCC) has poor prognosis due to lack of effective and safe approach. In 2002, Professor Wang Junjie introduced CT-guidance into the field of LDR-BT, and fully applied 3D printing technology in BT in 2015, which met the requirement of preoperative LDR-BT planning, and significantly improving the precision, quality and efficiency of BT. In 2018, Professor Wang Junjie proposed the concept of stereotactic ablation brachytherapy (SABT). Chinese experts have attempted to treat RCC with BT for nearly two decades and accumulated certain clinical experience. Based on the 3D-printing template (3D-PT) assisted CT-guidance, the standard and consensus of BT for RCC were established, including the indications, dosimetric requirements, technological procedures and radiation protection, etc. At present, there is still a lack of phage Ⅲ clinical and evidence-based medicine for the treatment of RCC with 3D-PT guidance, which requires prospective multi-center, randomized studies to improve the evidence-based level of BT.

Objective:To investigate the efficacy and adverse effects of pegylated recombinant human granulocyte colony-stimulating factor (PEG-rhG-CSF) in preventing neutropenia in patients undergoing sequential adjuvant radiotherapy after postoperative chemotherapy for breast cancer.Methods:A total of 43 female patients with breast cancer from January 2017 to January 2019 in Shandong Cancer Hospital and Institute were analyzed prospectively. Twenty-one patients in the experimental group were given 6 mg of PEG-rhG-CSF subcutaneously 1-3 days before radiotherapy. In the control group, 22 patients were enrolled without PEG-rhG-CSF utilization. The lowest absolute neutrophil count (ANC), the number of days of radiotherapy interruption due to neutropenia, the number of recombinant human granulocyte colony-stimulating factor (rhG-CSF) used during radiotherapy and the occurrence of drug-induced skeletal muscle pain in the two groups were statistically analyzed.Results:No neutropenia fever was observed in the two groups during radiotherapy. In the experimental group, there was no case of grade Ⅲ neutropenia; while in the control group, there were 3 cases of grade Ⅲ neutropenia. The median value of the lowest ANC in the experimental group was 1.56×10 9/L, higher than that in the control group (1.37×10 9/L), with a statistically significant difference ( Z=-2.261, P=0.023). The median number of rhG-CSF used in the experimental group was 1, which was smaller than 2 in the control group, and the difference was statistically significant ( Z=-2.498, P=0.012). The median numbers of days of radiotherapy interruption due to neutropenia were 0 and 3 in the experimental group and the control group, with a statistically significant difference ( Z=-3.117, P=0.001). One case (4.8%) of drug-induced skeletal muscle pain was found in the experimental group and 5 cases (22.7%) in the control group, with no statistically significant difference ( χ2=1.586, P=0.208). Conclusion:PEG-rhG-CSF can effectively prevent neutropenia caused by radiotherapy after postoperative chemotherapy for patients with breast cancer, and can reduce the interruption of radiotherapy and the use of rhG-CSF during radiotherapy, which is helpful to the smooth process of radiotherapy.

Objective:To discuss the feasibility of using online and offline combined multidisciplinary team (MDT) diagnosis-treatment mode in cancers diagnosis and treatment by comparing the comprehensive diagnosis and treatment plans formulated by online and offline MDT diagnosis-treatment mode.Methods:A total of 168 esophageal cancer patients collected from March 17, 2020 to May 17, 2020 were took as the research objects in Shandong Cancer Hospital and Institute, through whom the consistency of the comprehensive diagnosis and treatment plans formulated by online and offline MDT diagnosis-treatment mode was evaluated. The clinical characteristics of patients with changed comprehensive diagnosis and treatment plans, such as age, Karnofsky performance status (KPS) score, whether combined with basic diseases, whether received anti-tumor treatment before and tumor location were analyzed, so as to explore the mechanism to improve the efficiency on the basis of quality assurance.Results:The results showed that 86.3% (145/168) of the comprehensive diagnosis and treatment plans obtained by offline MDT diagnosis-treatment mode were consistent with online diagnosis-treatment MDT mode. Cases with inconsistent comprehensive diagnosis and treatment plans were characterized by elderly (> 69 years) ( χ2=4.250, P=0.039), KPS score≥80 ( χ2=15.520, P<0.001) and combined with underlying disease ( χ2=7.135, P=0.008). Through further analysis, the changed cases were also characterized as with inadequate auxiliary examination or complex in imaging. Conclusion:The online and offline combined MDT diagnosis-treatment mode is feasible. For the patients characterized of elderly (> 69 years old), KPS score ≥80, combined with underlying diseases, with incomplete auxiliary examination or complex in imaging, the offline MDT diagnosis-treatment mode should be adopted or supplemented.

Objective To observe the long-term effect,adverse reaction and cosmetic outcome of early-stage breast cancer with hypofractionated whole-breast irradiation (HF-WBI) after breast-conserving surgery.Methods A total of 206 patients with stage 0-Ⅱ breast cancer after breast-conserving surgery were included in Shandong Cancer Hospital Affiliated to Shandong University from May 2014 to August 2017.According to radiotherapy fraction,patients were divided into HF-WBI group and conventional whole-breast irradiation (CF-WBI) group.In HF-WBI group,116 patients received whole-breast radiation to 42.56 Gy in 16 fractions followed by tumor bed boost of 9 Gy in 3 fractions or 10 Gy in 5 fractions.In CF-WBI group,90 patients received whole breast radiation to 50 Gy in 25 fractions followed by tumor bed boost of 10 Gy in 5 fractions.The 2-year local recurrence rate,2-year mortality rate,acute adverse reaction,late adverse reaction and cosmetic outcome of the two groups were analyzed.Results The 2-year local recurrence rates of HF-WBI group and CF-WBI group were 0.86％ (1/116) and 2.22％ (2/90) respectively,and there was no significant difference between the two groups (x2 =0.049,P =0.824).The 2-year mortality rates of the two groups were 0.86％ (1/116) and 0 (0/90) respectively,and there was no significant difference (P ＞ 0.999).There were 108 cases (93.1％) in HF-WBI group and 84 cases (93.3％) in CF-WBI group with grade 0-1 acute dermatitis,and 8 cases (6.9％) and 6 cases (6.7％) with grade 2-3 respectively,with no statistically significant difference (x2 =0.004,P =0.948).There were 97 cases (83.6％) in HF-WBI group and 79 cases (87.8％) in CF-WBI group with grade 0-1 bone marrow suppression,and 19 cases (16.4％)and 11 cases (12.2％) with grade 2-4 respectively,with no statistically significant difference (x2 =0.704,P =0.401).In the two groups,there were 1 case (0.9％) and 3 cases (3.3％) with grade 1-2 radiation pneumonitis,and 115 cases (99.1％) and 87 cases (96.7％) with no radiation pneumonitis respectively,and the difference was not statistically significant (x2 =1.626,P =0.202).There was 1 case (0.9％,1.1％) with grade 1 breast edema in each group,and 115 cases (99.1％) and 89 cases (98.9％) did not occur breast edema,with no statistically significant difference (x2 =0.033,P =0.857).In the late adverse reactions,there were 5 cases (4.3％) and 3 cases (3.3％) with skin pigmentation in HF-WBI group and CF-WBI group respectively.There were 2 cases (1.7％,2.2％) with grade 1 subcutaneous tissue fibrosis in each group,and there were 1 case (0.8％) and 2 cases (2.2％) with grade 1 pulmonary fibrosis respectively.The differences between the two groups were not statistically significant (x2 =0.000,P ＞ 0.999;x2 =0.000,P ＞ 0.999;x2 =0.049,P =0.824).The 6-month,1-year and 2-year cosmetic outcome good rates in HF-WBI and CF-WBI group were 96.5％ (111/115) and 93.3％ (84/90),92.1％ (105/114) and 90.0％ (81/90),91.4％ (53/58) and 87.2％ (41/47) respectively.The differences between the two groups were not statistically significant (x2 =0.526,P =0.468;x2 =0.277,P =0.599;x2 =0.476,P =0.490).The whole course of radiotherapy time in HF-WBI group was 25 days or 29 days,which was significantly shorter than the 40 days of CF-WBI group.Conclusion HF-WBI after breast-conserving surgery has the similar long-term effect,acute and late adverse reaction and cosmetic outcome compared with CF-WBI,and the treatment time is significantly shorter.It can be further promoted as the optimal adjuvant radiotherapy for early-stage breast cancer after breast-conserving surgery.

Objective: To investigate the curative effect and prognostic factors of radical radiotherapy for cervical cancer. Methods: A total of 211 patients with stage Ⅰ_A-Ⅲ_B cervical cancer who underwent therapy in department of radiotherapy, Tumor Hospital of Jilin province between June 2014 and February 2017, were analyzed retrospectively. All patients received radical radiotherapy with or without concurrent chemotherapy. Short-term and long-term efficacy and related prognostic factors were observed. Kaplan-Meier method was used for survival analysis, Log-rank test was used for univariate analysis, and Cox proportional hazards regression model was used for multivariate analysis. Results: The 2-year overall survival (OS) and disease free survival (DFS) were 83.4% and 72.5%, respectively. During the follow-up periods, 46 patients (21.8%) died, including two from non-tumor-related diseases, and one from second primary colon cancer. Totally 57 patients (27%) had recurrence and metastasis, including 16 (28.1%) with local recurrence, 27 (47.4%) with distant metastasis, and 14 with local recurrence and distant metastasis(24.6%). Univariate analysis showed that 2-year OS and DFS were significantly correlated with pathological type, pre-treatment squamous cell carcinoma antigen (SCC) value and FIGO stage (OS: χ²=7.123, 6.014, 8.398, P<0.05; DFS: χ²=11.832, 8.003, 7.731, P<0.05). In addition to the above factors, 2-year DFS was also associated with pelvic lymph node metastasis (χ²=9.286, P<0.05). Multivariate analysis showed that pathological type, pre-treatment SCC value and FIGO stage were independent prognostic factors of OS(HR=2.963, 2.473, 2.574, P<0.05). The independent prognosis factors affecting DFS included pathological type, pre-treatment SCC value and pelvic lymph node metastasis (HR =3.014, 1.988, 1.914, P<0.05). Conclusions By means of radical radiotherapy, cervical cancer patients with adenocarcinoma, pre-treatment SCC levels ≥30 ng/ml and advanced stage have poor prognosis, so more active treatment strategy should be adopted.