Objective To describe and analyze the epidemiological characteristics of scrub typhus in Huai'an, Jiangsu Province from 2006 to 2024 and explore the long-term incidence trend and distribution of high-risk areas, and to formulate targeted prevention and control strategies. Methods The scrub typhus case report data of Huai'an from 2006 to 2024 in the Chinese Disease Prevention and Control Information System were extracted for descriptive analysis. Results A total of 898 cases of scrub typhus were reported in Huai'an, with an average annual incidence rate of 0.96 per 100 000 from 2006 to 2024. There was a turning point in the incidence trend of scrub typhus in 2011. From 2006 to 2011, the annual percentage change (APC) was 47.09% (95% CI: 7.53 - 859.39), and the upward trend was statistically significant (P < 0.05). From 2012 to 2024, the APC was -2.12% (95% CI: -29.09 - 3.75), and the downward trend was not statistically significant. October and November were the high-incidence months, and the total concentration from 2006 to 2024 was 0.93, indicating that scrub typhus had strict seasonality. The circular distribution method estimated that the peak period of the epidemic was from October 11th to November 25th, and the peak day of incidence was November 3rd. Jinhu County was a high-incidence area. The ratio of male to female cases was 1.03. The age group with the highest reported incidence was 40 to < 80 years old. The occupation with the highest proportion was farmers, accounting for 78.03%. Conclusion From 2006 to 2024, scrub typhus in Huai'an shows a peak every 3 - 4 years. Middle-aged and elderly farmers are the key population at risk, and Jinhu County is a key area. In the future, targeted health education should be carried out to effectively control the prevalence of scrub typhus.

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.

Objective:To preliminarily explore the role of silent information regulator 3 (SIRT3) in ferroptosis induced by high glucose in renal tubular epithelial cells, and to provide a new theoretical basis and treatment ideas for renal tubular injury in diabetic kidney disease patients.Methods:The single-cell transcriptomic analysis from "Tabula-muris" database was used to evaluate the expression of SIRT3 gene in different cellular subtypes of kidney tissues. HK-2 cells, a human immortalized proximal tubule epithelial cell line, were cultured in vitro and divided into following groups: (1) control group, mannitol group and high glucose group; (2) control group, negative control group, SIRT3 overexpression group, high glucose group and SIRT3 overexpression + high glucose group; (3) control group, negative control group, SIRT3 knockdown group, high glucose group and SIRT3 knockdown + high glucose group; (4) control group, Erastin intervention group and SIRT3 overexpression + Erastin intervention group. Normal glucose was 5.5 mmol/L, high glucose was 30 mmol/L, mannitol was 24.5 mmol/L, Erastin was 10 μmol/L, and the intervention time was 48 h. Cell counting kit-8 proliferation and cytotoxicity assay was used to determine cell viability. Real-time quantitative PCR and Western blotting were performed to assess the expression of SIRT3, kidney injury molecule-1 (KIM-1), and ferroptosis-related proteins acyl-CoA synthetase long chain family member 4 (ACSL4) and glutathione peroxidase 4 (GPX4) at the mRNA and protein levels. The malondialdehyde, glutathione, and iron levels were measured to evaluate the degree of cellular ferroptosis. DCFH-DA was used to analyze the intracellular reactive oxygen species level, while the JC-1 staining method was employed to evaluate alterations of mitochondrial membrane potential in HK-2 cells. Results:(1) The results of single-cell transcriptomic database analysis demonstrated that SIRT3 gene was expressed at the highest level in the subtypes of proximal tubule epithelial cells of kidney tissues. (2) Compared with the control group, the expression levels of KIM-1 and ACSL4 were higher, and the expression levels of SIRT3 and GPX4 and cell viability were lower in the high glucose group (all P<0.05), while there was no statistically significant difference of the aforementioned indicators between the mannitol group and the control group (all P>0.05). (3) Compared with the high glucose group, HK-2 cell vitality, GPX4 expression and intracellular glutathione were higher, ACSL4 expression, intracellular iron, malondialdehyde and reactive oxygen species were lower, mitochondrial membrane potential partially recovered in SIRT3 overexpression + high glucose group (all P<0.05). Compared with the high glucose group, HK-2 cell vitality and GPX4 expression were lower, ACSL4 expression was higher in SIRT3 knockdown + high glucose group (all P<0.05), and there were no statistically significant differences in intracellular iron, malondialdehyde and glutathione (all P>0.05). (4) Compared with the control group, Erastin intervention group had upregulated ACSL4 expression and downregulated GPX4 expression in HK-2 cells (all P<0.05). Compared with the Erastin intervention group, SIRT3 overexpression + Erastin intervention group had upregulated GPX4 expression and downregulated ACSL4 expression (all P<0.05). Conclusions:High glucose can decrease SIRT3 expression and mitochondrial membrane potential, and increase oxidative stress and ferroptosis in HK-2 cells. Overexpression of SIRT3 may reduce oxidative stress and alleviate mitochondrial dysfunction, thereby mitigating glucose-induced ferroptosis in HK-2 cells.

Abstract OBJECTIVE To establish an efficient and simple HPLC-MS/MS method for determination of flucloxacillin in newborn plasma, and to investigate the interaction between ambroxol and flucloxacillin in newborns. METHODS The samples were analyzed by API4000 HPLC-MS/MS. Ultimate XB-C18 column(2.1 mm×100 mm, 5 μm) were carried out. The mobile phase was composed of water-0.1% formic acid(A) and acetonitrile-0.1% formic acid(B). The quantitative analysis of the ion transitions were monitored at m/z 452.6→284.2 for flucloxacillin and m/z 821.4→397.3 for rifampicin(internal standard). RESULTS The linear range of flucloxacillin under this analysis method was 0.20-80 ng·mL-1, and the lower limit of quantification was 0.20 ng·mL-1; The intra-day and inter-day precision of flucloxacillin were both less than 8.23%; The extraction recovery was in the range of 85.3%-89.2%, and the matrix effect was between 89.3%-92.3%; The stability of plasma samples was good under conditions of 12 h at room temperature, 4 h at room temperature after treatment, repeated freeze-thaw for 3 times, and -20 ℃ freezing for 30 d. The results of clinical samples indicated that the combination of ambroxol could significantly increase the blood concentration of flucloxacillin. CONCLUSION The established HPLC-MS/MS method is accurate, sensitive and can be used for the determination of flucloxacillin concentration in neonatal plasma. The results of clinical samples indicate that ambroxol can significantly increase the blood concentration of flucloxacillin. There are drug interactions between ambroxol and flucloxacillin.

OBJECTIVE：To study the effects o f CYP2C9*3 gene polymorphism on therapeutic efficacy of benzbromarone in lowering uric acid and its hepatotoxicity. METHODS ：A retrospective study was conducted to analyze the relevant clinical indicators and genotypes of 196 gout patients who received benzbromarone and CYP2C9*3 gene polymorphism test in Wuhan third hospital from Jan. 2018 to Sept. 2019. RESULTS ：Among 196 patients，179，15 and 2 patients with CYP2C9*3 genotypes * 1/*1， *1/*3 and * 3/*3 genotypes were found ，respectively，and the distribution of each genotype was in line with Hardy-Weinberg balance（P＞0.05）. Before treatment ，there were no significant differences in the levels of UA ，Scr，ALT，AST and CRP between *1/*1 genotype and * 1/*3+*3/*3 genotype（P＞0.05）. After 4 weeks of treatment ，the UA ，Scr，CRP levels of patients with * 1/*1 genotype as well as the UA and CRP levels of patients with * 1/*3+*3/*3 genotype were significantly reduced ，the UA level of patients with * 1/*1 genotype was significantly lower than that of patients with * 1/*3+*3/*3 genotype（P＜0.05 or P＜0.01）. The ALT and AST levels had no obvious changes in patients with different genotype before and after treatment ，and they were in the normal range. No serious abnormal liver function was observed during the treatment. CONCLUSIONS ：Therapeutic efficacy of benzbromarone in lowering uric acid in gout patients with CYP2C9*3 genotypes * 1/*1 genotype is better than that of * 1/*3 and * 3/*3 genotypes. However ，the gene polymorphism may be not associated with its hepatotoxicity.