OBJECTIVES: To explore the effect of quercetin for mitigating HIV-1 gp120-induced astrocyte neurotoxicity and its underlying mechanism. METHODS: Primary rat astrocytes were isolated and treated with quercetin, HIV-1 gp120, or gradient concentrations of quercetin combined with HIV-1 gp120. The formation of stress granules (SGs) in the treated cells was observed with immunofluorescence assay, and the levels of oxidative stress markers and protein expressions were measured using specific assay kits and Western blotting. HIV-1 gp120 transgenic mice were treated with quercetin (50 mg/kg) by gavage for 4 weeks, and the changes in cognitive functions and oxidative stress levels were examined by behavioral assessments, oxidative stress index analysis in serum, and immunohistochemical and Western blotting of the brain tissue. RESULTS: In primary rat astrocytes, treatment with quercetin significantly reduced HIV-1 gp120-induced SG formation, increased the levels of antioxidant indexes, decreased the levels of oxidative substances, and up-regulated protein level associated with SG depolymerization. In the transgenic mouse models, quercetin obviously improved the cognitive function of the rats, reduced oxidative stress levels, and promoted the expression of proteins associate with SG depolymerization in the brain tissues. CONCLUSIONS Quercetin mitigates HIV-1 gp120-induced astrocyte neurotoxicity and cognitive function impairment by inhibiting oxidative stress, enhancing expressions of SG depolymerization-related proteins, and promoting SG disassembly, suggesting the value of quercetin as a potential therapeutic agent for neuroprotection in HIV-associated neurocognitive disorders.
Animals ; Quercetin/pharmacology* ; Astrocytes/metabolism* ; HIV Envelope Protein gp120 ; Oxidative Stress/drug effects* ; Rats ; Stress Granules/drug effects* ; Mice ; Mice, Transgenic ; Rats, Sprague-Dawley ; Cells, Cultured

Objective:To explore the optimal duration of preoperative imatinib therapy in patients with locally advanced gastrointestinal stromal tumors (GIST) in order to optimize surgical timing and long-term survival benefits.Methods:A total of 171 patients with locally advanced GIST who received preoperative imatinib therapy and subsequent surgical resection between November 2012 and October 2024 at Fujian Cancer Hospital and Union Hospital of Fujian Medical University were retrospectively analyzed. Patients were divided into three groups according to the duration of preoperative imatinib treatment: short-term (≤6 months, n=50), intermediate-term (7-12 months, n=87), and long-term (>12 months, n=34). Imaging response, pathological efficacy, recurrence-free survival (RFS), and overall survival (OS) were compared among the groups. Univariate and multivariate Cox regression analyses were used to identify the optimal treatment duration. Results:The median duration of preoperative imatinib therapy was 9 (6, 12) months. After treatment, the average maximum tumor diameter decreased from (10.37±5.74) cm to (6.99±4.34) cm, with an average shrinkage of 31.5%. The objective response rates in the short-, intermediate-, and long-term groups were 50.0% (25/50), 58.6% (51/87), and 52.9% (18/34), respectively; high-grade pathological response rates were 28.0% (14/50), 37.9% (33/87), and 29.4% (10/34), with no statistically significant differences among groups (all P>0.05). With a median follow-up of 46 months, 39 patients experienced recurrence and 20 died. The intermediate-term group had 3- and 5-year RFS rates of 87.1% and 79.6%, respectively, significantly better than those of the short-term group (75.5% and 55.5%, P=0.004). The long-term group had 3- and 5-year RFS rates of 85.3% and 75.5%, which were between the other two groups, but not significantly different (all P>0.05). For OS, the intermediate-term group had 3- and 5-year rates of 97.3% and 92.7%, superior to the short-term group (84.4% and 72.4%, P=0.007), while the long-term group (88.2% and 79.4%) showed no significant advantage (all P>0.05). Stratified analysis revealed that among non-gastric primary tumor patients with c-Kit exon 11 mutations, partial response on imaging, or postoperative imatinib ≤24 months, the intermediate-term group had significantly better RFS and OS than the short-term group (all P<0.05), but had no differences compared to the long-term group ( P>0.05). Multivariate Cox regression analysis indicated that preoperative imatinib duration was not an independent factor for RFS ( P>0.05), but treatment for 7-12 months was an independent protective factor for OS ( HR=0.275, 95% CI: 0.089-0.851, P=0.025), while prolonging therapy beyond 12 months conferred no additional OS benefit ( P>0.05). Conclusions:In patients with locally advanced GIST, preoperative imatinib therapy for 7-12 months yielded the most favorable prognosis, with significantly improved RFS and OS compared to ≤6 months of treatment. Extending preoperative therapy beyond 12 months did not provide additional survival benefit.

Objective:To explore the dosimetric characteristics of intensity modulated proton therapy (IMPT), intensity modulated radiation therapy (IMRT) and tomotherapy (TOMO) techniques applied in the irradiation of pediatric whole central nervous system tumors.Methods:Taking the target area of a 14-year-old pediatric patient clinically diagnosed with atypical teratoid/rhabdomyoid tumor, meningeal metastasis by Shandong Cancer Hospital and Institute, and undergoing craniospinal irradiation (CSI) as an example, IMPT, IMRT and TOMO plans were designed respectively based on the clinical prescription of the target area and the limit requirements of organs at risk (OARs). The conformal index (CI), homogeneity index (HI) and gradient index (GI) of each planning target volume, as well as the dose volume index of normal tissues, were evaluated to compare the dosimetric characteristics of the three types of plans.Results:The CI (0.71), HI (0.05) and GI (3.13) of the IMPT plan were comparable to those of IMRT plan (0.80, 0.08, 3.14). The HI (0.03) and GI (2.54) of the TOMO plan were excellent, which were all within the clinically acceptable range. The irradiation dose to parallel organs in the IMPT plan was lower than that in the IMRT and TOMO plan. In the IMPT plan, V 5 of lungs was 2.9%, IMRT plan was 37.6%, and TOMO plan was 43.5%. The D mean of liver in the IMPT plan was 0.01 Gy (RBE), IMRT plan was 6.12 Gy, and TOMO plan was 6.39 Gy. In the IMPT plan, none of the bladder, rectum, and femoral head received the dose, while there was low-dose radiation in both IMRT and TOMO plan. For serial organs adjacent to and within the target area, the D max of spinal cord and brainstem in IMPT plan was 39.89 and 39.88 Gy (RBE), respectively; in IMRT plan, they were 39.43 and 38.59 Gy, respectively; and in TOMO plan, they were 38.41 and 37.69 Gy, respectively. The low-dose area in the IMPT plan was significantly better than the photon radiotherapy plans. Among them, the absolute volume IMPT plan occupied by 10% of the prescribed dose area in the patient's body was reduced by 70.10% compared with IMRT plan and 76.96% compared with TOMO plan; the 30% prescribed dose volume IMPT plan was reduced by 53.49% compared with IMRT plan and 62.51% compared with TOMO plan; the 50% prescribed dose volume IMPT plan was reduced by 39.06% compared with IMRT plan and 42.23% compared with TOMO plan. Conclusions:The IMPT plan demonstrated significantly reduced low-dose exposure and lower doses to parallel OARs compared to both IMRT and TOMO plans in pediatric CSI. The CI, HI and GI of the three plans can all meet the clinical requirements. However, for serial organs adjacent to and within the target area, the D max of the IMPT plan may be higher than that of IMRT and TOMO plans.

Objective:To explore the dosimetric characteristics of proton and photon radiotherapy in the treatment of breast cancer.Methods:Four female breast cancer patients who needed radiotherapy at Shandong Cancer Hospital and Institute from January 2024 to May 2024 were selected as the research subjects. The target area ranges of 4 patients were left-sided breast cancer with lymph node involvement, left-sided breast cancer with lymph node involvement and internal mammary node, right-sided breast cancer with lymph node involvement and internal mammary node and synchronous bilateral breast cancer. Intensity modulated proton therapy (IMPT) and intensity modulated radiation therapy (IMRT) plans were designed respectively based on the prescribed dose in the target area and the limits of organs at risk (tomotherapy plan for bilateral breasts). The conformity index (CI), homogeneity index (HI), gradient index (GI) and organs at risk doses were evaluated. The dosimetric characteristics of IMPT and photon radiotherapy were compared.Results:Both IMPT and photon radiotherapy plans of the 4 breast cancer cases met the clinical dose requirements. The HI value of IMPT plans (0.10-0.14) was comparable to that of photon radiotherapy plans (0.10-0.12), and the average CI of the photon radiotherapy plans was 0.10 higher than that of the IMPT plans, and the average GI was 0.55 lower than that of the IMPT plans. The D mean of ipsilateral lung and heart of IMPT was lower, especially in the low-dose area (V 0-3), which was significantly lower than the photon radiotherapy plans, D mean of ipsilateral lung was reduced by 12.2%, 6.1%, 16.1% and 34.8%, respectively, D mean of heart was reduced by 47.2%, 57.0%, 72.4% and 83.0%, respectively. The ipsilateral lung V 20 of IMPT was not lower than photon radiotherapy plans (unilateral breast: IMPT was 30.0%-34.0%, IMRT was 29.0%-35.9%) . Conclusions:IMPT significantly reduces the D mean to the ipsilateral lung and heart while ensuring dose coverage of the target in breast cancer, preventing more volume of surrounding normal tissues from being irradiated. However, IMPT does not show much more advantage than photon radiotherapy plans in the ipsilateral lung V 20.

Objective:To explore the dosimetric characteristics of intensity modulated proton therapy (IMPT) and intensity modulated radiation therapy (IMRT) for typical abdominal and pelvic tumors.Methods:Three patients with abdominal and pelvic tumors (one case each of liver cancer, cervical cancer, and prostate cancer) admitted to Shandong Cancer Hospital and Institute from January to June 2024 were selected as the research subjects. IMPT and IMRT plans were designed for each case based on clinical target volume (CTV) and organs at risk (OARs) constraints. Dosimetric parameters, including conformity index (CI), homogeneity index (HI), and gradient index (GI) for target coverage, as well as OARs dose metrics, were evaluated. The volume of additional dose deposition in the body was compared by assessing regions receiving 10%, 30%, and 50% of the prescription dose.Results:For all three cases, IMRT plan demonstrated higher CI values (0.82, 0.81, and 0.86) compared to IMPT plan (0.61, 0.62, and 0.43). IMPT plan yielded lower HI values (0.053, 0.075, and 0.020) than IMRT plan (0.060, 0.120, and 0.080) and lower GI values (3.45, 2.63, and 3.80 vs. 7.28, 4.76, and 4.66 for IMRT plan). In liver cancer, IMPT plan reduced the D mean of normal liver tissues and right kidney by 37.8% and 78.5%, respectively, and decreased the D max of spinal cord by 13.2%. For cervical cancer, IMPT plan reduced the V 30 of the small bowel by 22.0%, D mean of the bladder, rectum and bone marrow by 15.7%, 14.3% and 12.6%, and spinal cord D max by 4.8%. In prostate cancer, IMPT plan lowered bladder and rectal D mean by 14.9% and 36.5%, respectively, but resulted in an increase of 35.3% and 6.1% in the D mean and V 40 of the left femoral head, respectively, and an increase of 23.6% and 10.8% in the D mean and V 40 of the right femoral head, respectively. IMPT plan reduced the volumes receiving 10%, 30%, and 50% of the prescription dose by 48.9%-64.8%, 22.0%-47.0%, and 22.0%-57.7%, respectively, compared to IMRT plan. Conclusions:Comparison between IMPT and IMRT plans for abdominopelvic tumors: IMPT plan offers advantages in reducing doses to normal organs such as the liver, kidneys, spinal cord, small intestine, rectum, and bladder. However, its advantage is less pronounced regarding the dose to the femoral heads. IMPT plan notably minimizes additional dose deposition within the body.

Objective:To investigate the dosimetric characteristics of intensity modulated proton therapy (IMPT) and photon volumetric modulated arc therapy (VMAT) in typical head and neck malignant tumors.Methods:Three types of typical head and neck tumors (nasopharyngeal carcinoma, parotid gland carcinoma, laryngeal carcinoma) treated at Shandong Cancer Hospital and Institute from December 2023 to December 2024 were taken as research subjects. IMPT and VMAT radiotherapy plans were created according to clinical prescription requirements of target and organs at risk limits respectively. The conformity index (CI), homogeneity index (HI) and gradient index (GI) for target coverage of two radiotherapy plans were evaluated for 3 patients, as well as the dosimetric indicators of organs at risk.Results:The CI of IMPT for nasopharyngeal carcinoma, parotid gland carcinoma and laryngeal carcinoma were 0.70, 0.72 and 0.67, respectively. The HI were 0.11, 0.08 and 0.08, respectively. The GI were 3.08, 2.49 and 3.75, respectively. The CI of VMAT plans were 0.77, 0.82 and 0.91, respectively. The HI were 0.12, 0.10 and 0.04, respectively. The GI were 3.67, 2.63 and 3.45, respectively. The results showed that CI of IMPT plan was slightly lower than that of VMAT plan, and HI of IMPT plan was comparable to that of VMAT plan, the GI of the IMPT plan for patients with nasopharyngeal carcinoma and parotid gland carcinoma was lower than that of the VMAT plan, and the GI of the IMPT plan for patient with laryngeal carcinoma was higher than that of the VMAT plan, and all were within the clinically acceptable range. The IMPT plan has demonstrated significant dose advantages in the treatment of nasopharyngeal carcinoma, parotid gland carcinoma and laryngeal carcinoma. For patient with nasopharyngeal carcinoma, the IMPT plan reduced the D max of the left and right crystals by 54.1% and 50.4%, respectively, compared to VMAT plan, and reduced the D mean of the oral and laryngeal tissues by 40.5% and 49.6%, respectively. For patient with parotid gland carcinoma, IMPT plan reduced the D max of the brainstem and spinal cord by 66.2% and 40.5%, respectively, compared to VMAT plan. For patient with laryngeal carcinoma, IMPT reduced spinal cord D max by 77.0%, while thyroid cartilage D mean increased by 8.0% compared to VMAT plan. For the additional dose in the patients' body, taking the absolute volumes occupied by the prescribed dose areas of 10%, 30%, and 50% in the patients' body as examples, IMPT plan of nasopharyngeal carcinoma patient decreased by 29.7%, 29.6%, and 34.9% compared to VMAT plan, respectively. IMPT plan of parotid gland carcinoma patient decreased by 61.0%, 39.7%, and 17.4% compared to VMAT plan, respectively. IMPT plan of laryngeal carcinoma patient decreased by 63.9%, 31.7%, and 4.1% compared to VMAT plan, respectively. Conclusions:Compared with VMAT plan, IMPT plan can effectively reduce the irradiation dose of most organs at risk near the target of head and neck tumors, but the dose of string organs close to the target area may be higher, which needs attention.

Objective:To investigate the dosimetric characteristics of intensity modulated proton therapy (IMPT) and intensity modulated radiation therapy (IMRT) for lung cancers.Methods:Three lung cancer patients (central-lower, central, and peripheral types) admitted to Shandong Cancer Hospital and Institute from January 2024 to May 2024 were selected as the research subjects. IMPT and IMRT plans were designed for each case based on the anatomical location of the clinical target volume and the dose constraints for organs at risk (OARs). Dosimetric parameters, including conformity index (CI), homogeneity index (HI), and gradient index (GI) for target coverage, as well as OARs dosimetric parameters were evaluated. The volume of additional dose deposition in the body was compared by assessing regions receiving 10%, 30%, and 50% of the prescription dose.Results:For all three cases, IMRT plans demonstrated higher CI values (0.80, 0.60, and 0.79) compared to IMPT plans (0.61, 0.57, and 0.34). IMPT plans yielded lower HI values (0.07, 0.06, and 0.06) than IMRT plans (0.09, 0.15, and 0.09) and lower GI values (2.84, 2.47, and 4.56 vs. 4.91, 3.09, and 4.99 for IMRT plans). Compared with the IMRT plans, the low-dose region in the ipsilateral lung was significantly reduced in IMPT plans (V 5 of the IMPT plans were 20.59%, 46.29%, 10.94%, respectively; V 5 of the IMRT plans were 48.91%, 60.63%, 19.92%, respectively), but there was no significant advantage in the high-dose region compared to IMRT plans (V 20 of the IMPT plans were 12.88%, 34.75%, 5.21%, respectively; V 20 of the IMRT plans were 21.70%, 36.50%, 5.31%, respectively). The dose to the contralateral lung and heart was significantly reduced in IMPT plans [the D mean of the contralateral lung in the IMPT plans were 0.08, 0.04, and 0.00 Gy (RBE), respectively, and those in the IMRT plans were 3.25, 1.18, and 0.55 Gy, respectively; the heart D mean in the IMPT plans were 6.23, 7.04, and 0.00 Gy (RBE), respectively, while those of the IMRT plans were 18.33, 10.27, and 0.08 Gy, respectively). IMPT plans significantly reduced the volumes receiving 10% of the prescription dose by 65.94%, 25.57% and 72.47%, respectively, compared to IMRT plans. The volumes IMPT plans occupied by 30% of the prescription dose area in the body were reduced by 54.97%, 26.47% and 39.04%, respectively, compared to the IMRT plans. The volumes IMPT plans occupied by 50% of the prescription dose area in the body were reduced by 54.49%, 30.43% and 28.89%, respectively, compared to the IMRT plans. Conclusions:IMPT plan significantly reduces the V 5 of the ipsilateral lung, the D mean of the contralateral lung and the heart, while maintaining target coverage compared with IMRT plan for lung cancers. However, IMPT plan does not show much more advantage than IMRT plan in the ipsilateral lung V 20. IMPT can reduce the additional exposure volume within the body.

Objective:To explore the dosimetric characteristics of proton radiotherapy plan and photon radiotherapy plan for esophageal cancer.Methods:Four patients who were admitted to Shandong Cancer Hospital and Institute from January 2024 to April 2024 with esophageal cancer (cervical, middle thoracic and total esophageal tube, as well as the lymphatic drainage areas involved) and required radiotherapy were selected as the research subjects. Intensity modulated proton therapy (IMPT) and intensity modulated radiation therapy (IMRT) plans were designed respectively based on the clinical target volume and the dose constraints for organs at risk (OARs). Dosimetric parameters, including conformity index (CI), homogeneity index (HI), gradient index (GI) for target coverage, as well as OARs dosimetric parameters were evaluated. The volume of additional dose deposition in the body was compared by assessing regions receiving 10%, 30%, and 50% of the prescription dose.Results:For all four cases, IMPT plans yielded lower HI values (0.12, 0.10, 0.06, and 0.08) than IMRT plans (0.15, 0.13, 0.10, and 0.11), and the GI values of IMPT plans (3.11, 3.21, 2.43, and 2.72) was lower than IMRT plans (4.52, 5.14, 3.09, and 3.92). Moreover, the CI of the IMPT plans (0.59, 0.60, 0.77, and 0.72) was inferior to IMRT plans (0.81, 0.77, 0.91, and 0.85). Compared with the IMRT plans, in the whole lung dose indicators of the IMPT plans for the 4 patients, V 5 decreased by 34.1%, 55.0%, 79.7% and 60.3%, respectively; V 20 decreased by 48.3%, 43.9%, 65.8% and 40.8%, respectively, and D mean decreased by 43.4%, 57.2%, 76.2% and 45.4%, respectively. V 30 of the heart decreased by 36.2%, 45.3%, 40.1% and 52.4%, respectively, and D mean of heart decreased by 96.6%, 57.9%, 58.5% and 55.3%, respectively. For the middle and lower thoracic target area, the liver was significantly protected in the IMPT plan (D mean decreased by 76.0% compared with the IMRT plan). In terms of the additional dose deposition in the patient's body, IMPT plans reduced the volumes receiving 10%, 30% and 50% of the prescription dose by 45.0%-61.4%, 41.2%- 61.8% and 34.8%-61.6%, respectively, compared with the IMRT plans. Conclusions:By comparing the dosimetric parameters of IMPT and IMRT plans for 4 cases of esophageal cancer, the IMPT plans have advantages in reducing the doses to lung tissue, heart, and liver, and can also reduce additional dose deposition in the patient's body.

Malakoplakia is a rare granulomatous inflammatory disease，Almost 75% of cases of malakoplakia mainly affect the genitourinary tracts，and a small proportion affect the intestines. Its occurrence in the adrenal gland is extremely rare. We report a case of adrenal malakoplakia. Who was presented to the hospital for chronic left upper abdominal pain and fever. The patient was admitted to our hospital due to the discovery of a huge mass in the left adrenal gland by CT. Pathological features of Michaelis Gutmann bodies（M-G bodies）were observed through adrenal biopsy，which revealed adrenal Malakoplakia. E. coli was cultured from both blood and the pus in the left renal parenchymal aera. After regular antibiotics treatment，the patient's fever symptoms improved compared to before. CT imaging showed that the adrenal mass had decreased in size，indicating effective treatment. Adrenal malakoplakia is easily misdiagnosed as malignant disease because of its radiological occupying performance. And its gold standard is pathology. For patients with symptoms of infection，we recommend urine，blood，pus in the pararenal area culture tests，and treatment with sensitive antibiotics according to the results of drug sensitivity testing.

Objective To explore the value of inflammatory load index(IBI)in the diagnosis and prognosis of gastric cancer patients.Methods Clinical data of patients who underwent gastric cancer surgery in the Department of General Surgery of the Second Hospital of Lanzhou University from January 2016 to December 2018 were retrospectively analyzed,and the patients were divided into the high IBI group and the low IBI group based on the optimal cut-off value of IBI.ROC curve was used to determine the optimal cut-off value of IBI,and the survival curve was constructed using the Kaplan-Meier method,and the differences between groups were examined using the Log-rank test.Cox regression analysis was performed to study the prognostic factors of gastric cancer patients.Results The best cut-off value for IBI diagnosis was 8.796,and the best cut-off value for prognosis was 28.75.IBI was related to the clinical case characteristics of gastric cancer patients,such as surgical access,the degree of differentiation,CK7,CK20,LMP-1,and Ki-67(P＜0.05).The results of univariate analysis showed that intraoperative bleeding,preoperative CEA,preoperative CA125,preoperative CA199,IBI,tumor diameter size,margins of incision,vascular invasion,nerve invasion,pT stage and pN stagewere the influencing factors on the prognosis of gastric cancer patients(P＜0.05).The results of multifactorial regression analysis showed that intraoperative bleeding,preoperative CEA,preoperative CA199,IBI,tumor diameter size,pT stage and pN stagewere independent risk factors affecting the prognosis of gastric cancer patients(P＜0.05).The median OS of patients in the high IBI group and low IBI group were 32.9 months and 74.8 months,respectively,with statistically significant differences(P＜0.001).Conclusion IBI is an independent risk factor for poor prognosis of patients with gastric cancer,and it has a good predictive value in diagnosis and prognosis.