OBJECTIVE: To study effective methods for reducing lung V₅, V₁₀, and mean lung dose (MLD) in the design of volumetric modulated arc therapy for central lung cancer by using different arc configurations and dose-limiting blocks designs. METHODS: Five groups of plans were designed for the enrolled patients. Group A used a full-arc field. Group B used a partial-arc field. Groups C, D, and E used full-arc fields with vertical-length, semi-ring, and triangular dose-limiting blocks added respectively. The dosimetric similarities of target areas and the dosimetric differences in lung V₅, V₁₀, V₂₀, and MLD among the groups were compared. RESULTS: Compared with group A, groups B, C, D, and E had decreased homogeneity and conformity of the target area, but significantly lower V₅ and V₁₀ of the whole lung. The MLD of groups C, D, and E was lower than that of group A. CONCLUSION Using a full-arc field combined with dose-limiting blocks can effectively reduce lung V₅, V₁₀, MLD, and monitor units (MU).
Lung Neoplasms/radiotherapy* ; Humans ; Radiotherapy, Intensity-Modulated/methods* ; Radiotherapy Planning, Computer-Assisted/methods* ; Radiotherapy Dosage ; Lung/radiation effects*

Objective:To explore the radiological damage to cells induced by the delayed particles of 9C-ions for heavy ion therapy, as well as the microdosimetric distribution and biological effects of these particles on a single model of V79 Chinese hamster lung cells. Methods:The Monte Carlo program was employed to simulate the endonuclear absorbed doses of α particles with various energies (3-10 MeV) transported in cells (cell radius RC = 10 μm, nucleus radius RN = 5 μm). Then, the result were compared with the S values ( SN←N, SN←Cy, and SN←CS) derived using the medical internal radiation dose (MIRD) method to demonstrate the feasibility of Monte Carlo simulations. Finally, the energy deposition of the delayed particles of 9C-ions generated at three sites (i.e., on the surface and in the cytoplasm and nucleus of the V79 cell model) during their transport in targets was simulated, and the result ing cell surviving fraction was analyzed. Results:Monte Carlo and MIRD method yielded differences in S values of 1.91%-4.95% for SN←N (nucleus to nucleus), 1.48%-5.11% for SN←Cy (cytoplasm to nucleus), and -1.99% to 0.80% for SN←CS(surface to nucleus), indicating highly consistent S values derived using both method(differences < 6%). When a 9C-ion decayed on the surface of the V79 cell model and the produced secondary particles entered the cell, the average endonuclear absorbed dose was 10 -2 Gy orders of magnitude, with a cell surviving fraction of about 88%. In the case where decay occurred in the cytoplasm, the cell surviving fraction was about 80%. However, when the 9C ion decayed in the nucleus, α particles had short ranges and deposited most of their energy in the cell (mean endonuclear absorbed dose: 0.1 Gy). In this case, severe cell damage was induced, with the cell surviving fraction reducing to about 53%. Conclusions:9C-ions emit secondary charged particles due to decay, among which α particles cause great damage to cells when entering the nucleus and trigger evident biological effects.

Objective:To analyze the relevant records of Taibai (SP3) in ancient literature based on data mining technology; To summarize its application law.Methods:Ancient book materials included in the Zhong Hua Yi Dian (5th edition) were retrieved. Relevant information of Taibai (SP3) such as main treatment syndrome and compatibility of acupoints was extracted, and a database was established. The frequency of the data was counted. Gephi 0.10.1 software and SPSS Statistics 21.0 statistical software were used to carry out visualization analysis and clustering analysis on data. Results:A total of 248 articles were included, involving 43 ancient books, including 65 prescriptions for single acupoint application and 183 prescriptions for compatibility application. The main treatment of Taibai (SP3) involved internal medicine, surgery, gynecology and infectious diseases. There were 35 kinds of main treatment of single acupoint, and 12 kinds of dominant diseases, including vomiting, fever and dysentery. There were 47 kinds of main diseases and 14 kinds of dominant diseases such as fever, heartache and constipation. There were 138 acupoints, most of which were specific acupoints, mainly the spleen meridian, and the high frequency acupoints were Zusanli (ST36), Dadu (SP2), Gongsun (SP4) and so on. Clustering analysis obtained 8 kinds of acupoint combinations, which were potential prescriptions for Taibai (SP3).Conclusion:Taibai (SP3) was widely used in clinical practice in ancient times, with 8 kinds of diseases such as fever, constipation and abdominal pain as the main dominant diseases, and most of them were compatible with specific acupoints such as Zusanli (ST36), Dadu (SP2), Gongsun (SP4).

Objective:To discuss dominant symptoms and compatibility rules of Dazhui(GV14) based on data mining.Methods:Literature related to Dazhui (GV14) was retrieved from CNKI, Wangfang, VIP, China Biomedical Literature Database (CBM) and Pubmed databases from January 1, 2012 to August 15, 2022, and the main symptoms of Dazhi (GV14) and the compatibility of acupoints were summarized. Gephi 0.9.5 software was used for complex network analysis to compare the treatment for dominant symptoms with single acupoint of Dazhi (GV14) and the compatibility of the acupoint. SPSS Modeler 18.0 software was used to analyze the association rules of acupoint combination based on Apriori algorithm. The clustering analysis of high frequency acupoints was carried out by SPSS Statistics 26.0 software.Results:A total of 722 articles were included, involving 732 prescriptions. The dominant symptoms of single acupoint were cervical spondylosis, acne, and cold; the treatment for dominant symptoms with compatibility included 14 types, such as cervical spondylosis, allergic rhinitis, ischemic stroke sequelae. The meridian compatibility was dominated by bladder meridian, and the frequency of yang meridians was higher than yin meridians. The compatibility of specific acupoints such as Xiahe acupoint, Beishu acupoint and Bahui acupoint were the main acupoints, and the high frequency acupoints were 33 acupoints such as Feishu (BL13), Baihui (GV20), Fengchi (GB20) and Zusanli (ST36), obtaining 4 series and 8 types of compatible combinations of Dazhui (GV14).Conclusions:Dazhui (GV14) is widely used in the treatment of internal diseases, such as respiratory diseases, nervous system diseases and vertebral artery type of cervical spondylosis. It tends to be flexibly used with multiple compatibility and clustering combination of specific acupoints.

Our recent studies for nonnucleoside reverse transcriptase inhibitors identified a highly potent compound JK-4b against WT HIV-1 (EC₅₀ = 1.0 nmol/L), but the poor metabolic stability in human liver microsomes (t _1/2 = 14.6 min) and insufficient selectivity (SI = 2059) with high cytotoxicity (CC₅₀ = 2.08 μmol/L) remained major issues associated with JK-4b. The present efforts were devoted to the introduction of fluorine into the biphenyl ring of JK-4b, leading to the discovery of a novel series of fluorine-substituted NH₂-biphenyl-diarylpyrimidines with noticeable inhibitory activity toward WT HIV-1 strain (EC₅₀ = 1.8-349 nmol/L). The best compound 5t in this collection (EC₅₀ = 1.8 nmol/L, CC₅₀ = 117 μmol/L) was 32-fold in selectivity (SI = 66,443) compared to JK-4b and showed remarkable potency toward clinically multiple mutant strains, such as L100I, K103N, E138K, and Y181C. The metabolic stability of 5t was also significantly improved (t _1/2 = 74.52 min), approximately 5-fold higher than JK-4b in human liver microsomes (t _1/2 = 14.6 min). Also, 5t possessed good stability in both human and monkey plasma. No significant in vitro inhibition effect toward CYP enzyme and hERG was observed. The single-dose acute toxicity test did not induce mice death or obvious pathological damage. These findings pave the way for further development of 5t as a drug candidate.

Objective:To investigate the safety and efficacy of individualized transperineal prostate biopsy based on the segmentation of PI-RADS v2 for mpMRI.Method:The clinical data of patients undergoing prostate biopsy in Beijing Friendship Hospital from December 2018 to November 2021 were analyzed retrospectively . A total of 228 patients with a median age of 65(49-83)years underwent biopsy. There were 102(44.7%) with tPSA <10 ng / ml, 108(47.4%) with tPSA 10-20 ng /ml, and 18(7.9%) with tPSA >20 ng /ml, with the median tPSA of 9.87(4.1-89.0)ng /ml. There were 42(18.4%) cases without MRI results, and 32(14.0%)cases with PI-RADS score of 1-2, 47(20.6%)cases of PI-RADS 3, 66(28.9%)cases of PI-RADS 4 and 41(18.1%)cases of PI-RADS 5, respectively.Transrectal ultrasound-guided transperineal prostate targeted biopsy (TB) and systematic biopsy (SB) were performed under local anesthesia or intravenous anesthesia. SB was performed for those without MRI and PI-RADS score of 1-2 (SB group), and TB and SB were performed for those with PI-RADS score of 3-5 (TB+ SB group). Prostate image under ultrasound was cognitively fused according to PI-RADS v2. One needle per area was distributed in 10 areas of each layer(the transition zone anterior and posterior sectors, the peripheral zone anterior, lateral, and medial sectors or central zone in left and right lobe). For those whose prostate length was less than 3cm, 10 needles were punctured, and two needles were added to each lateral lobe of the apex with a total of 14 needles. For those whose prostate length was from 3 to 6 cm, selected two layers with a total of 20 needles. For those with a length greater than 6cm, selected three layers with a total of 30 needles. If there was a suspicious lesion with PI-RADS score of 3-5, two needles were targeted for each lesion.The detection rate and complication rate of prostate cancer and clinically significant prostate cancer (csPCa) in the overall samples were observed, and the difference of the detection rate of prostate cancer and csPCa between the two groups was compared.Results:Of the 228 cases, there were 46 cases undergoing biopsy of one layer, 148 cases of two layers, and 34 cases of three layers, detecting 131 prostate cancer (PCa) diagnosed by pathology, with a detection rate of 57.5%, including 40 cases (17.5%)of clinically insignificant PCa and 91 cases(39.9%)of csPCa. The detection rate of PCa in TB+ SB group was 61.0%(94/154), which was higher than that in SB group, but there was no significant difference ( P=0.114). However, the detection rate of csPCa in TB + SB group was higher than that in SB group, which was 46.8%(72/154)vs. 25.6%(19/74), respectively ( P=0.002). In the combined TB and SB group (TB + SB group), the detection rate of csPCa by TB was 44.8% (69/154), which was higher than that of 33.8%(52/154)by SB( P=0.047). In the TB+ SB group, 7(4.5%) PCa were missed by SB, which was less than 18 cases (11.7%) missed by TB( P=0.022), but csPCa were missed by SB more than that missed by TB( P<0.001). There were 37 cases suffered from complications, with Clavien Dindo classification grade 1 of 29 cases (12.7%), grade 2 of 7 cases (3.1%), and grade 3 of 1 case(0.4%). Conclusions:Individualized transperineal prostate biopsy based on the segmentation of PI-RADS v2 for mpMRI is safe and reliable. Target biopsy by cognitive fusion can improve the detection rate of significant PCa. Systematic biopsy is also an important and essential supplement, which can detect prostate cancer missed by TB. Combined TB and SB are the best choice.

Objective:To explore the potential mechanism of PD-1 inhibitor P on RIMI from the perspective of immune microenvironment.Methods:To establish a mouse model of radiation-induced myocardial injury (RIMI), twenty C57BL/6 mice were randomly divided into 4 groups, 5 in each group. Group A was the healthy control group; Group B was the PD-1 inhibitor group; Group C was the simple irradiation group, with a heart irradiation of 15 Gy; Group D was the irradiation+ PD-1 inhibitor group. One month after irradiation, the mice were anesthetized and sacrificed. The morphological changes of myocardial tissues were observed by HE staining. The myocardial fibrosis was assessed by Masson staining. CD 3+ , CD 3+ CD 4+ , CD 3+ CD 8 lymphocyte subsets and cytokines (IL-4, IL-6, IL-17A, TNF-α, TGF-β 1 and INF-γ) levels were determined by flow cytometry. The apoptosis rate of myocardial cells was detected by TUNE. Results:One month after irradiation, there was no obvious myocardial fibrosis in group B, and collagen fibers were distributed in the interstitium of myocardial cells in groups C and D. Semi-quantitative analysis results showed that the myocardial collagen volume fraction (CVF) of groups A, B, C and D were (1.97±0.36)%, (2.83±1.03)%, (5.39±0.77)% and (7.72±1.43)%, respectively. The CVF between group A and group B was similar ( P=0.314), and the differences in CVF between the other groups were statistically significant (all P<0.05). Compared with group A, the absolute value and percentage of CD 3+ T lymphocytes were significantly increased in groups B, C and D (all P<0.01). The values in group D were significantly higher than those in group B and group C (all P<0.01); The absolute value and percentage of CD 3+ CD4 T lymphocytes were similar among four groups (all P>0.05); The absolute value and percentage of CD 3+ CD 8 T lymphocytes in group D were significantly higher than those in groups A, B and C (all P<0.001). The expression levels of IL-6, IL-17A, and TGF-β 1 in group D were significantly higher compared with those in groups A, B and C (all P<0.001). The apoptotic index was gradually increased in four groups, and the differences in apoptotic index among four groups were statistically significant (all P<0.001). Conclusion:PD-1 inhibitors can aggravate RIMI by promoting myocardial immune inflammatory response.

Objective:To study the effects of gantry acceleration limitations of a linear accelerator (linac) on the dosimetry of volumetric modulated arc therapy (VMAT) plans, machine efficiency, and dose verification result of VMAT plans and to explore the optimal selection of gantry motion models in the Pinnacle treatment planning system.Methods:Ten cases of nasopharyngeal carcinoma, non-small cell lung cancer, sigmoid adenocarcinoma with retroperitoneal lymph node metastasis, and invasive ductal carcinoma of the breast were each selected for this study. Then two models were set up in the Pinnacle v9.10 treatment planning system, namely the one allowing gantry acceleration and the one limiting gantry acceleration. The same field arrangement, optimized target parameters, and optimized weights of VMAT plans were adopted in the two models, in order to analyze the dosimetric variations in targets and organs at risk (OARs) and compare the differences in treatment time and gamma passing rates.Results:The treatment time of the enrolled patients under the model allowing gantry acceleration was significantly lower than that of the patients under the model limiting gantry acceleration was adopted ( t=-6.751, -0.209, -19.523, -28.999; P< 0.05) and decreased by 15.27%, 18.07%, 19.71%, and 28.75%, respectively. Meanwhile, the conformity and uniformity of target areas were affected, while there was no statistical significance in the gamma passing rates in the validation of VMAT plans ( P>0.05). For the cases of nasopharyngeal carcinoma (NPC), the maximum dose to brainstem PRV increased by 1.25%. For the cases of lung cancer, the maximum dose to the spinal cord and lung V20 increased by 1.19% and 1.21%, respectively, while lung V5 decreased by 1.21%. For the cases of sigmoid adenocarcinoma with retroperitoneal lymph node metastasis, the mean doses to bilateral kidneys, livers, small intestine, and colon all increased. For the cases of breast cancer, lung V10 on the opposite side of cancer increased by 1.66% and the mean dose to the lungs on the same side of cancer decreased by 7.45%. Conclusions:The model allowing gantry acceleration allows the treatment time to be significantly shortened and the treatment efficiency improved. Although this model had the shortcomings such as affecting the conformity and uniformity of target areas to a certain extent and increasing the doses to some OARs, clinical requirements for dosimetry were still met. Therefore, it is recommended to use the model allowing gantry acceleration in the Pinnacle planning system.

Objective:To investigate the primary tumor volume change and timing of radiotherapy for patients with stage Ⅳ non-small cell lung cancer with EGFR mutation during molecular targeted therapy.Methods:Simulated CT scanning measurement and analysis were performed to observe the volume changes of primary tumors before and after treatment with a time interval of 10 days in this prospective study. Positioning and volume measurement were terminated when the volume change was 5% or less between two time points before and after treatment or 90 days after treatment. Primary tumor radiation therapy was then performed, acute radiation-induced injury was recorded, and the implementation and simulation of related parameters of radiotherapy plans were compared.Results:Twenty-nine of 30 cases were included in the analysis (1 case dropped off). After EGFR-TKIs treatment, the volume of all primary tumors was decreased, but the shrinking rate was inconsistent with the speed. Until the last simulated CT scanning, the maximum and minimum shrinking rates were 90% and 28%, respectively. There was no case of termination within 30 days of treatment, and the average tumor volume was significantly decreased within 40 days and the average tumor volume significantly differed every 10 days ( P<0.001). After 40 days, the volume shrinking rate of primary tumors ≤5% gradually appeared, and one patient presented with a volume shrinking rate of >5% on 90 days. During this time, the average volume shrinking rate slowed down and became stable, ranging from 49.15% to 54.77%. Moreover, the average volume continued to gradually shrink after slight increase at 70 days. There was no significant difference in the average volume every 10 days ( P>0.05). After the termination of simulated CT scanning, the dose of primary tumor was (69±7) Gy for patients receiving radiotherapy. Two patients had grade 2 acute radiation-induced pneumonitis and 3 patients had grade 3 acute radiation-induced pneumonitis. In addition, 1 patient had grade 2 radiation-induced esophagitis. According to the technology and dose parameters of radiotherapy plan, simulated radiotherapy plans before and 40 days after EGFR-TKIs treatment were designed. The timing of implementation plan was significantly better than that before EGFR-TKIs treatment (all P<0.05), whereas it was similar to that at 40 days after EGFR-TKI treatment ( P>0.05). Conclusions:The primary tumor shrinking rate is gradually slowed down over time after EGFR-TKIs treatment in patients with stage Ⅳ non-small cell lung cancer. The average tumor volume is significantly decreased within 40 days and then the shrinking rate becomes slow. The tumor shrinking rate of each case is inconsistent. Radiotherapy at 40 days after treatment is probably the optimal timing to obtain high dose and control radiation-induced injury.

Objective:To explore a better indicator that can predict septic shock induced acute kidney injury (AKI) by combining renal resistive index (RRI) and central venous pressure (CVP).Methods:A prospective observational study was conducted. Patients with septic shock admitted to department of critical care medicine of Hebei General Hospital from November 2017 to October 2018 were enrolled. Baseline characteristics such as age, gender, underlying diseases, infection sites, acute physiology and chronic health evaluation Ⅱ(APACHEⅡ) in the first 24-hour, sequential organ failure assessment (SOFA) were recorded; Doppler-based RRI was obtained on the first day when hemodynamics was relatively stable, meanwhile the dose of norepinephrine and hemodynamic parameters were assessed. Urine output per hour, the total duration of mechanical ventilation, the length of intensive care unit (ICU) stay and 28-day mortality were also collected. Observational end point was death at discharge or the 28th day after ICU admission, whenever which came first. The patients were divided into AKI and non-AKI groups according to the 2012 Kidney Disease: Improving Global Organization (KDIGO) clinical practice guideline. The baseline and prognostic indicators, variables potentially associated with AKI were compared between the two groups. The variables independently associated with septic shock induced AKI were identified using multivariable Logistic regression. The predictive value of RRI and RRI combining CVP for AKI were analyzed by the receiver operating characteristic (ROC) curve.Results:A total of 107 patients were enrolled, with 59 patients in AKI group and 48 patients in non-AKI group. There was significant difference in RRI, CVP, percentage of norepinephrine dosage ≥0.5 μg·kg -1·min -1, procalcitonin (PCT), lactate (Lac), and serum creatinine (SCr) between the two groups. Logistic regression analysis showed that high CVP, RRI, Lac and PCT were independent risk factors for septic shock induced AKI [CVP: odds ratio ( OR) = 1.20, 95% confidence interval (95% CI) was 1.03-1.40, P = 0.022; RRI: OR = 3.02, 95% CI was 2.64-3.48, P = 0.006; Lac: OR = 2.43, 95% CI was 1.32-4.50, P = 0.005; PCT: OR = 1.20, 95% CI was 1.05-1.38, P = 0.009]. ROC curve analysis showed that the area under ROC curve (AUC) values of CVP≥9.5 mmHg (1 mmHg = 0.133 kPa) and RRI≥0.695 for predicting septic shock induced AKI were 0.656 and 0.662 respectively. The AUC value of the combination of RRI and CVP was greater compared with either RRI or CVP alone in predicting septic shock induced AKI, which AUC value was 0.712, 95% CI was 0.615-0.809, the sensitivity was 59% and the specificity was 75%. Conclusions:High CVP and RRI were independent risk factors for septic shock induced AKI. The combination of RRI and CVP performs poorly in predicting septic shock induced AKI. Further studies are needed to describe factors influencing Doppler-based assessment of RRI, which may help clinicians to prevent AKI early.