Objective:To investigate the relationship between serum apolipoprotein A1 (ApoA1), cytotoxic T lymphocyte-associated antigen-4 (CTLA-4), proinflammatory protein S100A9 (S100A9) and prognosis in patients with myelodysplastic syndrome (MDS).Methods:122 MDS patients visited Qinhuangdao First Hospital from January 2020 to January 2021 were selected as the research objects. After three years of follow up, patients were divided into survival group and death group based on survival status. The differences in ApoA1, CTLA-4, and S100A9 between the death group and the survival group were compared. Measurement data with normal distribution was expressed as " xˉ±s", independent sample t-test was used on comparison between groups. Counting data was expressed as rate or composition ratio, χ2 test was used on comparison between groups. Univariate and multivariate Logistic regression analysis were used to analyze factors related to death. Results:There was no lost to follow up patients after three years of follow up. Among those 122 patients, 92 survived and 30 died. The ratio of bone marrow primitive cells>5%, IPSS-R score, serum CTLA-4, and S100A9 levels in the survival group were (2.89±2.15), (3.13±1.95) points, (5.12±1.59) μg/L, (1643.98±429.65)ng/L, respectively, lower than (5.67±3.76), (5.12±2.36) points, (28.67±6.98) μg/L, (2895.64±553.62) ng/L in the death group ( t=5.03, 4.60, 30.27, 12.87, respectively, all P<0.01). The relative high-risk ratio of IPSS-R stratification in the survival group was 63.04%,(58/92) which was lower than the 86.67%(26/30) in the death group ( χ2=5.89, P=0.015). The absolute values of hemoglobin, lymphocytes and neutrophils, and values of platelets and ApoA1 in the survival group were(86.74±12.69)g/L, (1.41±0.23)×10 9/L, (1.42±0.55)×10 9/L, (59.98±21.37)×10 9/L, (1.09±0.40) g/L respectively, which were higher than (65.58±10.89)g/L, (0.68±0.17)×10 9/L, (0.96±0.31)×10 9/L, (42.85±20.95)×10 9/L, (0.91±0.36)g/L in the death group ( t=8.20, 16.00, 4.35, 7.90, 2.19; respectively, P<0.001, <0.001, <0.001, <0.001, =0.030). Multivariate Logistic regression model analysis showed that, bone marrow blasts cells>5% ( OR=1.732, 95% CI: 1.188~2.523, P=0.004), relatively high IPSS-R stratification ( OR=1.815, 95% CI: 1.332~2.474, P<0.001), high IPSS-R score ( OR=1.785, 95% CI: 1.259~2.529, P=0.001), high CTLA-4 level ( OR=2.156, 95% CI: 1.482~3.134, P<0.001) and high S100A9 level ( OR=1.787, 95% CI: 1.218~2.625, P=0.003) were risk factors for poor prognosis in MDS patients, while high ApoA1 level ( OR=0.785, 95% CI: 0.658~0.937, P=0.007) was a protective factor ( P<0.05). Conclusion:The decrease in ApoA1 levels and the increase in CTLA-4 and S100A9 levels in MDS patients are associated with poor prognosis.

Objective:In carbon ion treatment planning of water phantom, establish a conversion factor calculation system and conversion factor curves for organs at risk (OAR) for microdosimetric kinetic models (MKM) and local effect models (LEM), and validate them in clinical patient planning.Methods:Using a uniform spherical water phantom as the research object, relative biological effectiveness-weighted doses (RWD) for the LEM were re-calculated based on the physical dose of RayStation-MKM. The median dose within the planning target volume (PTV) of LEM and MKM was regarded as the conversion factor. The impacts of single-fraction target prescription dose, spread-out Bragg peak (SOBP) width and depth, shape, and irradiation mode on the conversion factor were assessed, and a conversion factor calculation system was established. Additionally, the accuracy of the conversion factor calculation system was validated using both water phantoms and clinical patient cases. The conversion factor curves for OAR were computed based on clinical patient treatment plans.Results:The primary influencing factors for the conversion factors were the single-fraction prescription dose, target SOBP width and depth. The conversion factors were increased with the increase of SOBP width and target depth, whereas decreased with the increase of the single-fraction prescription dose. Under single-field irradiation, a conversion factor calculation system was established based on above 3 parameters. For the plans of 9 patients, the average difference between the calculated results and the conversion factor calculation system was 0.340% ± 0.203%, and the average difference in the conversion curves for OAR was 2.650% ± 2.399%.Conclusion:A dose conversion factor calculation system and conversion factor curves for OAR for carbon ion radiotherapy are established for MKM and LEM, and their accuracy meets the requirements for use in clinical patient treatment plans.

Objective:To investigate the relationship between serum apolipoprotein A1 (ApoA1), cytotoxic T lymphocyte-associated antigen-4 (CTLA-4), proinflammatory protein S100A9 (S100A9) and prognosis in patients with myelodysplastic syndrome (MDS).Methods:122 MDS patients visited Qinhuangdao First Hospital from January 2020 to January 2021 were selected as the research objects. After three years of follow up, patients were divided into survival group and death group based on survival status. The differences in ApoA1, CTLA-4, and S100A9 between the death group and the survival group were compared. Measurement data with normal distribution was expressed as " xˉ±s", independent sample t-test was used on comparison between groups. Counting data was expressed as rate or composition ratio, χ2 test was used on comparison between groups. Univariate and multivariate Logistic regression analysis were used to analyze factors related to death. Results:There was no lost to follow up patients after three years of follow up. Among those 122 patients, 92 survived and 30 died. The ratio of bone marrow primitive cells>5%, IPSS-R score, serum CTLA-4, and S100A9 levels in the survival group were (2.89±2.15), (3.13±1.95) points, (5.12±1.59) μg/L, (1643.98±429.65)ng/L, respectively, lower than (5.67±3.76), (5.12±2.36) points, (28.67±6.98) μg/L, (2895.64±553.62) ng/L in the death group ( t=5.03, 4.60, 30.27, 12.87, respectively, all P<0.01). The relative high-risk ratio of IPSS-R stratification in the survival group was 63.04%,(58/92) which was lower than the 86.67%(26/30) in the death group ( χ2=5.89, P=0.015). The absolute values of hemoglobin, lymphocytes and neutrophils, and values of platelets and ApoA1 in the survival group were(86.74±12.69)g/L, (1.41±0.23)×10 9/L, (1.42±0.55)×10 9/L, (59.98±21.37)×10 9/L, (1.09±0.40) g/L respectively, which were higher than (65.58±10.89)g/L, (0.68±0.17)×10 9/L, (0.96±0.31)×10 9/L, (42.85±20.95)×10 9/L, (0.91±0.36)g/L in the death group ( t=8.20, 16.00, 4.35, 7.90, 2.19; respectively, P<0.001, <0.001, <0.001, <0.001, =0.030). Multivariate Logistic regression model analysis showed that, bone marrow blasts cells>5% ( OR=1.732, 95% CI: 1.188~2.523, P=0.004), relatively high IPSS-R stratification ( OR=1.815, 95% CI: 1.332~2.474, P<0.001), high IPSS-R score ( OR=1.785, 95% CI: 1.259~2.529, P=0.001), high CTLA-4 level ( OR=2.156, 95% CI: 1.482~3.134, P<0.001) and high S100A9 level ( OR=1.787, 95% CI: 1.218~2.625, P=0.003) were risk factors for poor prognosis in MDS patients, while high ApoA1 level ( OR=0.785, 95% CI: 0.658~0.937, P=0.007) was a protective factor ( P<0.05). Conclusion:The decrease in ApoA1 levels and the increase in CTLA-4 and S100A9 levels in MDS patients are associated with poor prognosis.

Objective:In carbon ion treatment planning of water phantom, establish a conversion factor calculation system and conversion factor curves for organs at risk (OAR) for microdosimetric kinetic models (MKM) and local effect models (LEM), and validate them in clinical patient planning.Methods:Using a uniform spherical water phantom as the research object, relative biological effectiveness-weighted doses (RWD) for the LEM were re-calculated based on the physical dose of RayStation-MKM. The median dose within the planning target volume (PTV) of LEM and MKM was regarded as the conversion factor. The impacts of single-fraction target prescription dose, spread-out Bragg peak (SOBP) width and depth, shape, and irradiation mode on the conversion factor were assessed, and a conversion factor calculation system was established. Additionally, the accuracy of the conversion factor calculation system was validated using both water phantoms and clinical patient cases. The conversion factor curves for OAR were computed based on clinical patient treatment plans.Results:The primary influencing factors for the conversion factors were the single-fraction prescription dose, target SOBP width and depth. The conversion factors were increased with the increase of SOBP width and target depth, whereas decreased with the increase of the single-fraction prescription dose. Under single-field irradiation, a conversion factor calculation system was established based on above 3 parameters. For the plans of 9 patients, the average difference between the calculated results and the conversion factor calculation system was 0.340% ± 0.203%, and the average difference in the conversion curves for OAR was 2.650% ± 2.399%.Conclusion:A dose conversion factor calculation system and conversion factor curves for OAR for carbon ion radiotherapy are established for MKM and LEM, and their accuracy meets the requirements for use in clinical patient treatment plans.

Objective:To perform FLASH irradiation experiments on cells and animals with carbon ion beams by updating the beam conditions and testing the performance of a clinical carbon ion therapy system.Methods:By using the vertical beam of the carbon ion therapy system and shortening the synchrotron beam extraction time to increase the current intensity, ultra-high dose rate beam could be achieved. Spreading the high current beam in the depth direction using a ridge filter and expanding it horizontally using point scanning technology could form the required field for cellular and animal experiments. The field flatness, penumbra, absorbed dose, average dose rate and other parameters were measured to verify whether the beam performance met the requirements.Results:The spread-out Bragg peak in the depth direction was consistent with the design, and the parameters such as field flatness and penumbra obtained by the measured lateral dose curve met the experimental requirements. After expansion, within a target volume of 20 mm×20 mm×10 mm, the absorbed dose in the field reaches 8 Gy, with the equivalent field dose rate of over 60 Gy/s and the maximum could reach 100 Gy/s. Within a target volume of 30 mm×30 mm×10 mm, the absorbed dose in the field is 4 Gy, and the equivalent filed dose rate of some energy in the field is greater than 40 Gy/s. In the experiment, the energy with a suitable dose rate can be selected for irradiation.Conclusion:After beam optimization, the carbon ion FLASH irradiation conditions for cytology and animal experiments can be realized on synchrotrons, and the beam performance parameters can meet the experimental requirements.

Idiopathic oligoasthenospermia （IO） has been increasingly emphasized in the diagnosis and treatment of male infertility. Oxidative stress damage directly affects sperm quality and spermatogenesis， constituting a major causative factor of IO. Firstly， due to its high content of polyunsaturated fatty acids， the sperm plasma membrane is highly sensitive to reactive oxygen species （ROS）， leading to lipid peroxidation accumulation and even inducing ferroptosis. Secondly， deficient downstream key proteins in the base excision repair pathway render sperm unable to repair extensive DNA oxidative damage under oxidative stress. Simultaneously， under oxidative stress， the apoptotic pathway of sperm is cascade-activated， causing rapid loss of motility. ROS further disrupts the hypothalamic-pituitary-gonadal axis， inhibiting testosterone production and ultimately affecting spermatogenesis. Wuzi Yanzongwan，in line with traditional Chinese medicine theory of treating IO through "nourishing kidney essence and harmonizing Yin and Yang"， clinically demonstrates its ability to improve sperm morphology， count， and motility， thereby enhancing male fertility. The research on the pharmacological constituents of Wuzi Yanzongwan primarily involves establishing a characteristic spectrum of Chinese medicine to achieve quality control and exploring the pharmacology of effective components. Studies have found that its main active ingredients consist of flavonoids and phenylpropanoids. Specifically， compounds such as hyperin， acteoside， kaempferol， and schisandrin A are identified as the primary active substances and quality control components. These compounds exhibit strong antioxidant activity and have been partly applied in research related to reproductive endocrine disorders. Tripterygium glycoside is primarily used for modeling of oxidative stress-induced IO. It leads to the accumulation of various lipid peroxides in testicular tissues and concurrently compromises the body's antioxidant capacity. Mechanistic studies have found that Wuzi Yanzongwan can inhibit elevated ROS levels in IO models and enhance the body's antioxidant capacity， thereby ameliorating inflammation， suppressing cell apoptosis， promoting testosterone production， and ultimately alleviating the decline in sperm quality and spermatogenesis caused by oxidative stress.

Objective:To examine follow-up data of different subgroups in order to further evaluate the performance and practical value of community colorectal cancer screening by detection of stool methylation syndecan-2 gene (m SDC2) among residents of Shipai Town, Dongguan City. Methods:This was an observational study. From May 2021 to February 2022, the Shipai Town government of Dongguan City completed screening for colorectal cancer by detection of stool m SDC2 in 10,708 residents from 18 villages who had met the initial screening criteria and been selected using whole population sampling. From May 2022 to February 2023, the research group conducted follow-up of participants about one year after the initial screening. Residents in the gray zone according to the initial screening were followed up by colonoscopy. Additionally, 1,000 residents with negative results on the initial screening were randomly sampled to undergo colonoscopy. Stool m SDC2 detection was performed again on residents who had had positive results on the initial screening, and colonoscopy was performed on those who again tested positive. Compliance with colonoscopy and detection of gastrointestinal lesions during follow-up were assessed in different subgroups. Results:Of the 438 residents in the gray zone on the initial screening, 155 underwent colonoscopy follow-up (colonoscopy compliance rate 35.4% [155/438]). These colonoscopies revealed that 27 (17.4%) of the participants had gastrointestinal lesions, including advanced adenomas in 22 cases (14.2%) and non-adenomatous polyps in two cases (3.2%). No colorectal carcinomas was identified. Of the 1, 000 randomly sampled residents with negative results on initial screening, 286 underwent colonoscopy follow-up (colonoscopy compliance rate 28.6% [286/1000]), These colonoscopies revealed that 11 (3.8%)of these individuals had gastrointestinal lesions, including three advanced adenomas (1.0%), five non-advanced adenomas (1.7%), one serrated adenoma or polyp (0.3%), and two non-adenomatous polyps (0.7%), but no colorectal carcinomas. Of the 821 residents who tested positive in the initial screening, 511 again underwent stool mSDC2 detection one year later (follow-up rate 62.2% [511/821]). Of these participants, 66 tested positive again (rate of 12.9% [66/511]), 39 (7.6%) of them in the gray zone, whereas 406(79.5%) tested negative. Forty-seven of the residents with positive results underwent colonoscopy (colonoscopy compliance rate 71.2% [47/66]), which revealed 36 (76.6%) gastrointestinal lesions, including 10 advanced adenomas (21.3%), nine non-advanced adenomas (19.1%) and 17 non-adenomatous polyps (36.2%).Conclusion:Stool m SDC2 detection performs well as a screening tool. In our study, colorectal cancer or precancerous lesions were extremely rare in participants who tested negative on the initial screening. However, some of the participants who tested in the gray zone on initial screening had precancerous colorectal lesions, particularly advanced adenomas, which would have been missed without follow-up colonoscopy. Of note, stool m SDC2 detection has good follow-up value in individuals who test positive on initial screening.

Objective:To examine follow-up data of different subgroups in order to further evaluate the performance and practical value of community colorectal cancer screening by detection of stool methylation syndecan-2 gene (m SDC2) among residents of Shipai Town, Dongguan City. Methods:This was an observational study. From May 2021 to February 2022, the Shipai Town government of Dongguan City completed screening for colorectal cancer by detection of stool m SDC2 in 10,708 residents from 18 villages who had met the initial screening criteria and been selected using whole population sampling. From May 2022 to February 2023, the research group conducted follow-up of participants about one year after the initial screening. Residents in the gray zone according to the initial screening were followed up by colonoscopy. Additionally, 1,000 residents with negative results on the initial screening were randomly sampled to undergo colonoscopy. Stool m SDC2 detection was performed again on residents who had had positive results on the initial screening, and colonoscopy was performed on those who again tested positive. Compliance with colonoscopy and detection of gastrointestinal lesions during follow-up were assessed in different subgroups. Results:Of the 438 residents in the gray zone on the initial screening, 155 underwent colonoscopy follow-up (colonoscopy compliance rate 35.4% [155/438]). These colonoscopies revealed that 27 (17.4%) of the participants had gastrointestinal lesions, including advanced adenomas in 22 cases (14.2%) and non-adenomatous polyps in two cases (3.2%). No colorectal carcinomas was identified. Of the 1, 000 randomly sampled residents with negative results on initial screening, 286 underwent colonoscopy follow-up (colonoscopy compliance rate 28.6% [286/1000]), These colonoscopies revealed that 11 (3.8%)of these individuals had gastrointestinal lesions, including three advanced adenomas (1.0%), five non-advanced adenomas (1.7%), one serrated adenoma or polyp (0.3%), and two non-adenomatous polyps (0.7%), but no colorectal carcinomas. Of the 821 residents who tested positive in the initial screening, 511 again underwent stool mSDC2 detection one year later (follow-up rate 62.2% [511/821]). Of these participants, 66 tested positive again (rate of 12.9% [66/511]), 39 (7.6%) of them in the gray zone, whereas 406(79.5%) tested negative. Forty-seven of the residents with positive results underwent colonoscopy (colonoscopy compliance rate 71.2% [47/66]), which revealed 36 (76.6%) gastrointestinal lesions, including 10 advanced adenomas (21.3%), nine non-advanced adenomas (19.1%) and 17 non-adenomatous polyps (36.2%).Conclusion:Stool m SDC2 detection performs well as a screening tool. In our study, colorectal cancer or precancerous lesions were extremely rare in participants who tested negative on the initial screening. However, some of the participants who tested in the gray zone on initial screening had precancerous colorectal lesions, particularly advanced adenomas, which would have been missed without follow-up colonoscopy. Of note, stool m SDC2 detection has good follow-up value in individuals who test positive on initial screening.

Ionizing radiation can induce the death of lymphatic endothelial cells, leading to structural damage, dysfunction, and reduction of lymphatic vessels, which poses a negative impact on radiotherapy. However, it can also induce tumor cells and tumor-infiltrated immune cells to secrete various cytokines and promote tumor-associated lymphangiogenesis, which favors anti-tumor therapy and improve anti-tumor immunity. Studying the changes in lymphatic vessels after ionizing radiation may be a way to explore the synergistic anti-tumor effects of radiotherapy and immunotherapy. This review summarized the morphological changes in lymphatics after ionizing radiation, the molecular mechanisms for the effects of ionizing radiation on lymphatic vessels, and the clinical value of lymphatic changes after ionizing radiation, aiming to provide ideas for the study of the effects of ionizing radiation on lymphatic vessels.

In recent years, heavy ion beams have received great attention in the field of malignant tumor radiotherapy due to their radiation physics and biological characteristics. The high rate of local tumor control is one of its advantages, but the control rate of metastatic lesions is still crucial in the treatment of most malignant tumors. Clinical studies on the combined conventional radiotherapy and immunotherapy suggest that the combination of the two can not only control the primary lesions, but may also reduce or completely eliminate distant metastatic lesions. High linear energy transfer radiation, especially heavy ion beams, may have stronger potential in combined immunotherapy. Therefore, this article focuses on the basic research progress of heavy ion beams regulating anti-tumor immune effects and their combined application with immunotherapy.