Objective: This study aimed to compare outcomes and adverse events of patients with locally advanced cervical cancer (LACC) undergoing concurrent chemoradiotherapy (CCRT) with cisplatin single-agent chemotherapy vs. CCRT with cisplatin combined with paclitaxel dualagent therapy. The primary outcomes are overall survival (OS), progression-free survival (PFS), local recurrence (LR), distant metastasis (DM) and the occurrence of adverse events. Methods: This retrospective cohort study included patients with FIGO 2009 stage IB1-IVA cervical squamous cell carcinoma undergoing radical CCRT. Patients were divided into groups A and B, treatment outcomes were compared between the two groups after 1:1 proportional propensity score matching. Results: Medical records of 1,203 patients were reviewed and 572 patients were finally included for propensity score matching. After propensity score matching, 121 pairs of patients were selected for analysis. The OS, PFS, LR and DM rates were 78.5% and 83.5% (p=0.417), 73.3% and 78.5% (p=0.312), 6.6% and 2.5% (p=0.123), 19% and 15.7% (p=0.497) for groups A and B, respectively. Further subgroup analysis according to stage and lymph node metastatic status showed no difference in survival between the two groups. The incidence of grade 3–4 acute haematological toxicities was different between the two groups (p<0.05). Conclusion Cisplatin combined with paclitaxel CCRT couldn’t improve the survival rates of patients with LACC. However, the hematological toxicity of combination chemotherapy is more severe but controllable. Cisplatin single-agent therapy remains the first choice for CCRT. Further prospective studies are indicated to provide evidence for the efficacy of cisplatin plus paclitaxel in dual-agent concurrent therapy.

OBJECTIVE To investigate the effects and potential mechanism of paeoniflorin on oxidative stress of ulcerative colitis （UC） mice based on adenosine monophosphate-activated protein kinase （AMPK）/nuclear factor-erythroid 2-related factor 2 （Nrf2） pathway. METHODS Male BALB/c mice were randomly divided into control group， model group， inhibitor group （AMPK inhibitor Compound C 20 mg/kg）， paeoniflorin low-， medium- and high-dose groups （paeoniflorin 12.5， 25， 50 mg/kg）， high- dose of paeoniflorin+inhibitor group （paeoniflorin 50 mg/kg+Compound C 20 mg/kg）， with 8 mice in each group. Except for the control group， mice in all other groups were given 4% dextran sulfate sodium solution for 5 days to establish the UC model. Subsequently， mice in each drug group were given the corresponding drug solution intragastrically or intraperitoneally， once a day， for 7 consecutive days. The changes in body weight of mice were recorded during the experiment. Twenty-four hours after the last administration， colon length， malondialdehyde （MDA） content， and activities of superoxide dismutase （SOD） and glutathione peroxidase （GSH-Px） in colon tissues were measured； histopathological morphology of colon tissues， tight junctions between intestinal epithelial cells， and histopathological scoring were all observed and evaluated； the mRNA expressions of AMPK and Nrf2， as well as the protein expressions of heme oxygenase-1（HO-1）， occludin and claudin-1， were all determined in colon tissue. RESULTS Compared with model group， paeoniflorin groups exhibited recovery from pathological changes such as inflammatory cell infiltration and crypt damage in the colon tissue， as well as improved tight junction damage between intestinal epithelial cells. Additionally， significant increases or upregulations were observed in body weight， colon length， activities of SOD and GSH-Px， phosphorylation level of AMPK， and protein expression of Nrf2， HO-1， occludin， claudin-1， and mRNA expressions of AMPK and Nrf2； concurrently， MDA content and histopathological scores were significantly reduced （P＜ 0.05 or P＜0.01）. In contrast， the inhibitor group showed comparable （P＞0.05） or worse （P＜0.05 or P＜0.01） indicators compared to the model group. Conversely， the addition of AMPK inhibitor could significantly reverse the improvement of high- dose paconiflorin （P＜0.01）. CONCLUSIONS Paeoniflorin can repair intestinal epithelial cell damage in mice， improve tight junctions between epithelial cells， upregulate the expression of related proteins， and promote the expression and secretion of antioxidant-promoting molecules， thereby ameliorating UC； its mechanism may be associated with activating AMPK/Nrf2 antioxidant pathway.

Objective: This study aimed to compare outcomes and adverse events of patients with locally advanced cervical cancer (LACC) undergoing concurrent chemoradiotherapy (CCRT) with cisplatin single-agent chemotherapy vs. CCRT with cisplatin combined with paclitaxel dualagent therapy. The primary outcomes are overall survival (OS), progression-free survival (PFS), local recurrence (LR), distant metastasis (DM) and the occurrence of adverse events. Methods: This retrospective cohort study included patients with FIGO 2009 stage IB1-IVA cervical squamous cell carcinoma undergoing radical CCRT. Patients were divided into groups A and B, treatment outcomes were compared between the two groups after 1:1 proportional propensity score matching. Results: Medical records of 1,203 patients were reviewed and 572 patients were finally included for propensity score matching. After propensity score matching, 121 pairs of patients were selected for analysis. The OS, PFS, LR and DM rates were 78.5% and 83.5% (p=0.417), 73.3% and 78.5% (p=0.312), 6.6% and 2.5% (p=0.123), 19% and 15.7% (p=0.497) for groups A and B, respectively. Further subgroup analysis according to stage and lymph node metastatic status showed no difference in survival between the two groups. The incidence of grade 3–4 acute haematological toxicities was different between the two groups (p<0.05). Conclusion Cisplatin combined with paclitaxel CCRT couldn’t improve the survival rates of patients with LACC. However, the hematological toxicity of combination chemotherapy is more severe but controllable. Cisplatin single-agent therapy remains the first choice for CCRT. Further prospective studies are indicated to provide evidence for the efficacy of cisplatin plus paclitaxel in dual-agent concurrent therapy.

Objective: This study aimed to compare outcomes and adverse events of patients with locally advanced cervical cancer (LACC) undergoing concurrent chemoradiotherapy (CCRT) with cisplatin single-agent chemotherapy vs. CCRT with cisplatin combined with paclitaxel dualagent therapy. The primary outcomes are overall survival (OS), progression-free survival (PFS), local recurrence (LR), distant metastasis (DM) and the occurrence of adverse events. Methods: This retrospective cohort study included patients with FIGO 2009 stage IB1-IVA cervical squamous cell carcinoma undergoing radical CCRT. Patients were divided into groups A and B, treatment outcomes were compared between the two groups after 1:1 proportional propensity score matching. Results: Medical records of 1,203 patients were reviewed and 572 patients were finally included for propensity score matching. After propensity score matching, 121 pairs of patients were selected for analysis. The OS, PFS, LR and DM rates were 78.5% and 83.5% (p=0.417), 73.3% and 78.5% (p=0.312), 6.6% and 2.5% (p=0.123), 19% and 15.7% (p=0.497) for groups A and B, respectively. Further subgroup analysis according to stage and lymph node metastatic status showed no difference in survival between the two groups. The incidence of grade 3–4 acute haematological toxicities was different between the two groups (p<0.05). Conclusion Cisplatin combined with paclitaxel CCRT couldn’t improve the survival rates of patients with LACC. However, the hematological toxicity of combination chemotherapy is more severe but controllable. Cisplatin single-agent therapy remains the first choice for CCRT. Further prospective studies are indicated to provide evidence for the efficacy of cisplatin plus paclitaxel in dual-agent concurrent therapy.

Aim To investigate the impact of Cinobu-facini on the proliferation,invasion,and apoptosis of HepG2 cells and the underlying mechanism.Methods The proliferation of HepG2 cells was assessed using the CCK-8 method following treatment with Cinobufaci-ni.The invasion capability of HepG2 cells was evalua-ted through Transwell assay after exposure to Cinobufa-cini.The apoptosis rates of HepG2 cells post Cinobufa-cini intervention were measured using flow cytometry,and the expression levels of VEGF in the culture medi-um of HepG2 cells were determined using enzyme-linked immunoassay.Furthermore,qRT-PCR and Western blot analyses were conducted to assess the im-pact of Cinobufacini on mRNA and protein expression levels related to the CXCL5/FOXD1/VEGF pathway.The interaction between CXCL5 and FOXD1 was inves-tigated via co-immunoprecipitation.Results Cinobufa-cini treatment led to a gradual decrease in HepG2 cell viability in a dose-dependent manner compared to the control group(P＜0.05).Moreover,Cinobufacini sig-nificantly suppressed HepG2 cell invasion(P＜0.05)while enhancing cell apoptosis(P＜0.05).Notably,Cinobufacini exhibited inhibitory effects on the CX-CL5/FOXD1/VEGF pathway,as evidenced by re-duced expression of related mRNA and proteins(P＜0.05).FOXD1 was identified as the binding site of CXCL5.Overexpression of CXCL5 resulted in in-creased proliferation and VEGF secretion by HepG2 cells(P＜0.05),and increased expression of FOXD1 and VEGF(P＜0.05).However,Cinobufacini inter-vention effectively inhibited liver cancer cell prolifera-tion and invasion(P＜0.05),promoted apoptosis(P＜0.05),reduced VEGF secretion by HepG2 cells(P＜0.05),and downregulated the expression of CXCL5 and FOXD1 in HepG2 cells(P＜0.05);but com-pared with the unexpressed group of Cinobufacini,its ability to inhibit cell activity was weakened(P＜0.05),and its ability to inhibit the expression of CX-CL5,FOXD1,and VEGF was weakened(P＜0.05).Conclusion Cinobufacini may inhibit HepG2 cell pro-liferation and invasion and promote HepG2 cell apopto-sis by regulating the CXCL5/FOXD1/VEGF pathway.

Objective:To explore the impact of the hospital health literacy environment on patients′ postoperative pain self-management behaviors, aiming to provide insights for hospitals to implement the Comprehensive Pain Management Pilot Work Program in hospitals and to promote self-health management among patients with other diseases or symptoms. Methods:From November to December 2023, a convenience sampling method was used to select postoperative patients from three grade A tertiary general hospitals in Zhejiang Province for an on-site questionnaire survey. The Chinese version of brief health literacy screen (BHLS), short-form health literacy environment scale (SF-HLES) and postoperative pain self-management behavior questionnaire (PPSMB) were used as survey tools to investigate the health literacy level of patients, the health literacy environment of the hospital, and the postoperative pain management behaviors of patients. Two-way ANOVA was used to compare the impact of different dimensions of the hospital health literacy environment on postoperative pain management behaviors among patients with different levels of health literacy. Multiple linear regression analysis was used to explore the relationship between the hospital health literacy environment, individual health literacy, and patients′ postoperative pain self-management behaviors, and to discuss the impact of individual health literacy on patients′ postoperative pain self-management behaviors under different hospital health literacy environments.Results:341 valid questionnaires were collected. The average score of the hospitals′ SF-HLES was (73.62±19.54) points. The average score of the patients′ BHLS was (9.65±2.88) points. The average score of the patients′ PPSMB was (25.99±6.35) points. Two-way ANOVA results showed that the interaction between individual health literacy and the clinical dimension ( F=5.463, P=0.020) and structural dimension ( F=6.470, P=0.011) of the hospital health literacy environment had a statistically significant impact on patients′ postoperative pain self-management behaviors, while the interaction with the interpersonal dimension ( F=0, P=0.984) had no statistically significant impact on pain self-management behaviors. Simple effect analysis indicated that only in the high health literacy environment of the clinical and structural dimensions did the difference in pain self-management behaviors between patients with good health literacy and those with limited health literacy had statistical significance ( P<0.001). Multiple linear regression analysis results showed that for each 1-point increase in the patients′ BHLS score, their PPSMB score increased by 3.74 points ( β1=0.832, P<0.001); for each 1-point increase in the hospital′s SF-HLES score, the patients′ PPSMB score could increase by 0.198 points ( β2=0.610, P<0.001). In a low health literacy environment, individual health literacy did not affect pain self-management behaviors ( P>0.05); however, in a high health literacy environment, for each 1-point increase in the patients′ BHLS score, their PPSMB score correspondingly increased by 4.037 points ( β4=0.317, P<0.001). Conclusions:The positive impact of individual health literacy on pain self-management is contingent upon a high-quality hospital health literacy environment. This suggests that optimizing the hospital health literacy environment is a necessary precondition for implementing the relevant content of the Comprehensive Pain Management Pilot Work Program and can provide a reference for promote self-health management among patients with pain and other diseases or symptoms.

Objective:To explore the produced-radiation brain damage in simulated solar particle events and to provide evidence for health risk assessment of radiation from manned deep space exploration.Methods:According to the main characteristics of solar particle events, mice were treated with total body irradiation (TBI) with 90 MeV protons in a dose range from 0.1 to 2 Gy, with irradiation dose of 0, 0.1, 0.3, 0.5, 1, 2 Gy, respectively. At 3 and 7 d after irradiation, the behavior of mice was examined using balance beam tests, rotarod tests, and new object recognition tests. Then, the density of dendritic spines and the number of Nissl bodies in the hippocampus were measured using Golgi and Nissl staining. The superoxide dismutase (SOD) activity, malondialdehyde (MDA) content, and neurotransmitter content in brain tissue were detected using the WST-8 method, TBA method, and high pressure liquid chromatography (HPLC), respectively. Besides, cell apoptosis was determined using the TUNEL method, and the dose-response relationship, a function of dose change with damage index, was analyzed using linear and linear square fitting method. Finally, the minimum radiation dose causing a significant change in all indicators of brain damage was determined as the brain damage threshold.Results:Compared to the control group, 1 Gy proton irradiation result ed in a significant decrease in the density of filopod dendritic spines ( t = 1.82, 2.30, P < 0.05) and a significant increase in abnormal Nissl bodies in the CA1 region ( t = 2.44, 3.77, P < 0.05). At 3 and 7 d after irradiation, as well as a significant increase in the DA ( t = 2.52, P<0.05) and Glu contents ( t = 4.04, P < 0.05) on day 7. In contrast, 2 Gy proton irradiation result ed in a decrease in SOD activity on day 3 ( t = 3.44, P < 0.05), and an increase in the MDA content ( t = 1.90, 2.14, P < 0.05), hippocampal cell apoptosis (t = 3.91, 3.54, P < 0.05), and 5-HT levels ( t = 2.81, 2.69, P < 0.05), together with a decrease in climbing time in the rotarod tests ( t = 2.85, 2.64, P<0.05) and propensity to recognize new objects ( t = 2.87, 2.84, P < 0.05) on days 3 and 7. Furthermore, a dose-response relationship was observed in the dose range from 0.1 to 2 Gy ( R2=0.74-0.99). Conclusions:The dose threshold of 90 MeV protons inducing brain damage in mice is inferred to be 1 Gy, and 14 dose-response models are developed, providing a biological basis for organ dose capping and risk assessment of crew experiencing short-term deep space flights.

Objective:To compare the difference of prognosis in ⅢCr stage cervical cancer patients with different T stage and lymph node status who received radical radiotherapy.Methods:Clinical data of 279 patients with ⅢCr stage cervical cancer treated with radical radiotherapy at Zhejiang Cancer Hospital from September 2013 to December 2016 were retrospectively analyzed. According to the latest American Joint Committee on Cancer (AJCC) TNM stage, all patients were divided into T 2a, T 2b, T 3a and T 3b stage groups, and N 1 and N 2 stage groups based on lymph node status. They were also divided into <1.85 cm and ≥1.85 cm groups according to the maximum short diameter of lymph node. In addition, they were assigned into ≤3 and>3 groups according to the number of lymph node metastasis. The differences of progression-free survival (PFS) and overall survival (OS) between patients with different T stage and lymph node status were compared by Kaplan-Meier test and log-rank test. Multivariate survival analysis was performed by Cox regression analysis. Results:Among 279 patients with ⅢCr stage cervical cancer receiving radical radiotherapy, 6 (2.2%) patients were diagnosed with stage T 2a stage, 109 (39.1%) patients with T 2b stage, 13 (4.7%) patients with T 3a stage, and 151 (54.1%) patients with T 3b stage. And 246 (88.2%) patients were diagnosed with N 1 stage and 33 (11.8%) patients with N 2 stage. According to the maximum short diameter of lymph nodes, there were 229 (82.1%) patients in the<1.85 cm group and 50 (17.9%) in the ≥1.85 cm group. According to the number of lymph node metastasis, there were 269 (96.4%) patients in the ≤3 group and 10 (3.6%) in the>3 group. There was no significant difference in the 5-year PFS ( P=0.136) and OS rates ( P=0.050) among patients with different T stages, and patients with T 3a stage had the worst prognosis (5-year OS rate was 38.5%). The 5-year PFS (48.0% vs. 64.2%, P=0.016) and OS rates (52.0% vs. 73.8%, P=0.001) in the ≥1.85 cm group were significantly lower than those in the<1.85 cm group. There was no significant difference in the 5-year PFS (61.0% vs. 63.6%, P=0.796) and OS rates (67.5% vs. 69.7%, P=0.770) between patients with N 1 and N 2 stages. There was no significant difference in the 5-year PFS (61.0% vs. 70.0%, P=0.653) and OS rates (67.3% vs. 80.0%, P=0.447) between patients in the number of metastatic lymph nodes ≤3 and>3 groups. The prognosis of patients with T 2b stage and the maximum short diameter ≥1.85 cm was the worst (5-year OS rate was 31.3%), while patients with T 2b stage and the maximum short diameter <1.85 cm obtained the best prognosis (5-year OS rate was 76.3%). Multivariate analysis showed that the maximum short diameter and radiation dose of lymph nodes were the independent relevant factors for the OS of ⅢCr stage cervical cancer patients (both P<0.05). Conclusions:Among ⅢCr stage cervical cancer patients receiving radical radiotherapy, clinical efficacy and prognosis significantly differ according to different T stage and lymph node status. Current staging system should be optimized to provide effective diagnostic and therapeutic regimens.

BACKGROUND:Laser therapy is a non-invasive and painless treatment that is considered to be an effective method suitable for the treatment of osteoarthritis due to its simplicity and non-invasive nature.Currently,the mechanism of action of laser therapy is unclear and the results of studies on its clinical application are controversial. OBJECTIVE:To review and summarize the latest research progress of laser therapy on chondrocytes,animal experiments and clinical efficacy,and to explore the possible mechanism of laser-mediated multi-pathway biological effects,so as to provide a theoretical basis for further research on the laser treatment of osteoarthritis of the knee joint. METHODS:A literature search was performed in CNKI,WanFang Data,VIP and PubMed databases for relevant literature published from 2018 to 2023,with"laser therapy,low level laser therapy,high level laser therapy,photobiomodulation,knee osteoarthritis,chondrocytes"as the search terms in Chinese and English,respectively.Together with 14 articles searched manually,70 articles were finally included for review. RESULTS AND CONCLUSION:Laser therapy in the treatment of knee osteoarthritis is mainly categorized into two types:low-level laser therapy and high-level laser therapy.Differences in laser parameters and treatment protocols have a direct impact on laser efficacy.When appropriate parameters are used,low-level lasers show positive effects in cellular experiments,animal models,and clinical efficacy.High-level lasers have been less studied in the treatment of knee osteoarthritis,but some preliminary clinical studies have shown positive results.Cell experiments have shown that low-level laser promotes chondrocyte proliferation and cartilage matrix synthesis,thereby reducing inflammatory response.Animal experiments have shown that low-level laser can reduce the release of pro-inflammatory factors,promote cartilage matrix synthesis,inhibit matrix degradation,and effectively improve the repair process of cartilage tissue.Low-level laser is also able to reduce oxidative stress damage and relieve pain in knee osteoarthritis.In clinical trials,both low-and high-level laser can reduce patients'pain and improve functional activities.The combination of laser therapy and exercise therapy modalities may improve the therapeutic effect.Lasers may affect intracellular signaling and cellular functions through photobiological or thermodynamic effects.This provides direct evidence that laser promotes articular cartilage regeneration.

ObjectiveTo explore the protective mechanism of paeoniflorin on mice with ulcerative colitis （UC） through the adenosine monophosphate-activated protein kinase （AMPK）/mammalian target of rapamycin （mTOR） autophagy pathway. MethodUC mouse model was established by allowing mice freely drink 4% DSS， and 56 BALB/c male mice were randomly divided into model group， AMPK inhibitor group （20 mg·kg^-1）， paeoniflorin （50 mg·kg^-1） + inhibitor （20 mg·kg^-1） group， and high dose （50 mg·kg^-1）， medium dose （25 mg·kg^-1）， and low dose （12.5 mg·kg^-1） paeoniflorin groups. After seven days of drug intervention， the protective effect of paeoniflorin on mice with UC was determined by comparing the body weight， disease activity index （DAI） changes， and Hematoxylin-eosin （HE） staining results. Enzyme linked immunosorbent assay （ELISA） was used to detect the levels of tumor necrosis factor-α （TNF-α） and interleukin-6 （IL-6） in the serum of mice in each group， and immunofluorescence was utilized to detect microtubule-associated protein 1 light chain 3 （LC3） content in the colon， AMPK， mTOR proteins， and their phosphorylated proteins including p-AMPK and p-mTOR in the colon tissue were detected by Western blot， and the mRNA expression levels of AMPK， mTOR， Beclin1， LC3， and p62 were detected by Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR）. ResultCompared with the blank group， the model group showed a decrease in body mass， an increase in DAI score， and severe pathological damage to the colon. The levels of inflammatory factors including TNF-α and IL-6 increased in serum （P<0.01）， while the protein levels of LC3 and p-AMPK/AMPK were down-regulated in colon tissue， and those of p-mTOR/mTOR were up-regulated （P<0.01）. The mRNA expression levels of AMPK and LC3 were down-regulated， while the mRNA expression levels of mTOR and p62 were up-regulated （P<0.01）. Compared with the model group and the paeoniflorin + inhibitor group， the mice treated with paeoniflorin showed an increase in body mass， a decrease in DAI score， a reduction in pathological damage to colon tissue， and a reduction in the levels of inflammatory factors of TNF-α and IL-6 in serum （P<0.05）. The protein levels of LC3 and p-AMPK/AMPK in colon tissue were up-regulated， while the protein levels of p-mTOR/mTOR were down-regulated （P<0.01）. The mRNA expression levels of AMPK， Beclin1， and LC3 were up-regulated， while the mRNA expression of mTOR and p62 were down-regulated （P<0.01）. The colon tissue of the inhibitor group was severely damaged， and the trend of various indicators was completely opposite to that of the high dose paeoniflorin group. ConclusionPaeoniflorin can enhance autophagy and reduce inflammatory damage in mice with UC by activating the AMPK/mTOR signaling pathway and thus play a protective role.