Objective:To explore the effects of deep hyperthermia on chemotherapy-related adverse effects and immune-inflammatory indicators in the patients undergoing postoperative adjuvant chemotherapy for colorectal cancer.Methods:This retrospective study included 52 patients who underwent surgery for colorectal cancer at the Affiliated Zhongshan Hospital of Dalian University from September 2021 to December 2023. The patients were divided into two groups based on treatment method: the combination group ( n=29) received postoperative adjuvant chemotherapy combined with deep hyperthermia, while the chemotherapy group ( n=23) received postoperative adjuvant chemotherapy alone. Both groups were treated with the XELOX regimen (oxaliplatin + capecitabine). The degree of bone marrow suppression during treatment was assessed by analyzing peripheral blood parameters, including hemoglobin, leukocyte count, neutrophil count, and platelet count. Immune-inflammatory indicators, including complement, procalcitonin (PCT), interleukin-6 (IL-6), systemic immune-inflammation index (SII), neutrophil-to-lymphocyte ratio (NLR), and platelet-to-lymphocyte ratio (PLR), were compared before and after treatment in both groups to evaluate the effects of deep hyperthermia on the immune-inflammatory response. Chi-square test or Fisher's exact test (two-tailed) was used to compare bone marrow suppression rates, and the immune-inflammatory indicators between the two groups were compared using t-tests or non-parametric tests, depending on whether the data conformed to a normal distribution. Results:In terms of myelosuppression, the incidence rates of moderate to severe decreases in leukocytes, neutrophils, platelets, and hemoglobin in the combination group were 31%, 31%, 21%, and 14%, respectively, compared to 52%, 61%, 48%, and 9% in the chemotherapy group. The change in PCT levels before and after treatment was significantly greater in the combination group than in the chemotherapy group ( P = 0.010). Both the combination group and the chemotherapy group showed significant reductions in SII, NLR and PLR after treatment, and the differences were statistically significant (all P < 0.05). The change in NLR before and after treatment was significantly greater in the combination group than in the chemotherapy group ( P = 0.031). Conclusions:Deep hyperthermia can alleviate chemotherapy-induced adverse effects such as thrombocytopenia and neutropenia in patients undergoing postoperative adjuvant chemotherapy for colorectal cancer. It also appears to improve the inflammatory response in these patients.

Objective To analyze the current status of medical services in secondary and tertiary hospitals in Shandong Province based on DRG,and to provide effective support for the implementation strategies of bidirectional referral.Methods The DRG group was used to analyze 42.348 3 million cases from 75 secondary hospitals and 69 tertiary hospitals in Shandong Province from 2019 to 2023.Experts were organized to establish standards for bidirectional referral of diseases.Results(1)35 high-frequency DRG disease groups with diagnosis,treatment ability and medical resources in secondary hospitals were selected,(2)The medical expenses and medical quality in the high-frequency DRG disease groups within secondary hospitals were lower than those in tertiary hospitals,(3)To develop standardized referral standards and programs with esophageal cancer as an example.Conclusion It is urgent to triage patients gradually and accurately through disease classification management,and formulate disease diagnosis and treatment plans and bidirectional referral standards to improve the medical quality of secondary hospitals.

Objective To analyze the current status of medical services in secondary and tertiary hospitals in Shandong Province based on DRG,and to provide effective support for the implementation strategies of bidirectional referral.Methods The DRG group was used to analyze 42.348 3 million cases from 75 secondary hospitals and 69 tertiary hospitals in Shandong Province from 2019 to 2023.Experts were organized to establish standards for bidirectional referral of diseases.Results(1)35 high-frequency DRG disease groups with diagnosis,treatment ability and medical resources in secondary hospitals were selected,(2)The medical expenses and medical quality in the high-frequency DRG disease groups within secondary hospitals were lower than those in tertiary hospitals,(3)To develop standardized referral standards and programs with esophageal cancer as an example.Conclusion It is urgent to triage patients gradually and accurately through disease classification management,and formulate disease diagnosis and treatment plans and bidirectional referral standards to improve the medical quality of secondary hospitals.

Objective:To explore the effects of deep hyperthermia on chemotherapy-related adverse effects and immune-inflammatory indicators in the patients undergoing postoperative adjuvant chemotherapy for colorectal cancer.Methods:This retrospective study included 52 patients who underwent surgery for colorectal cancer at the Affiliated Zhongshan Hospital of Dalian University from September 2021 to December 2023. The patients were divided into two groups based on treatment method: the combination group ( n=29) received postoperative adjuvant chemotherapy combined with deep hyperthermia, while the chemotherapy group ( n=23) received postoperative adjuvant chemotherapy alone. Both groups were treated with the XELOX regimen (oxaliplatin + capecitabine). The degree of bone marrow suppression during treatment was assessed by analyzing peripheral blood parameters, including hemoglobin, leukocyte count, neutrophil count, and platelet count. Immune-inflammatory indicators, including complement, procalcitonin (PCT), interleukin-6 (IL-6), systemic immune-inflammation index (SII), neutrophil-to-lymphocyte ratio (NLR), and platelet-to-lymphocyte ratio (PLR), were compared before and after treatment in both groups to evaluate the effects of deep hyperthermia on the immune-inflammatory response. Chi-square test or Fisher's exact test (two-tailed) was used to compare bone marrow suppression rates, and the immune-inflammatory indicators between the two groups were compared using t-tests or non-parametric tests, depending on whether the data conformed to a normal distribution. Results:In terms of myelosuppression, the incidence rates of moderate to severe decreases in leukocytes, neutrophils, platelets, and hemoglobin in the combination group were 31%, 31%, 21%, and 14%, respectively, compared to 52%, 61%, 48%, and 9% in the chemotherapy group. The change in PCT levels before and after treatment was significantly greater in the combination group than in the chemotherapy group ( P = 0.010). Both the combination group and the chemotherapy group showed significant reductions in SII, NLR and PLR after treatment, and the differences were statistically significant (all P < 0.05). The change in NLR before and after treatment was significantly greater in the combination group than in the chemotherapy group ( P = 0.031). Conclusions:Deep hyperthermia can alleviate chemotherapy-induced adverse effects such as thrombocytopenia and neutropenia in patients undergoing postoperative adjuvant chemotherapy for colorectal cancer. It also appears to improve the inflammatory response in these patients.

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.

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.