Background and purpose:The ripple filter(RiFi)is a passive energy modulator used in particle beam therapy to broaden the Bragg peak.The 1D-RiFi features a wavy structure that can broaden a monoenergetic carbon ion beam to 3 mm,while the 2D-RiFi employs a two-dimensional groove structure to achieve a 6 mm beam broadening.This study aimed to evaluate the potential advantages of the 2D-RiFi over the 1D-RiFi in terms of dose distribution optimization,treatment efficiency,and organ at risk(OAR)dose control by comparing water phantom and clinical patient plans.Methods:Carbon ion treatment plans were designed for water phantoms and 20 patients using both 1D-RiFi and 2D-RiFi.The water phantom plans targeted a cubic region of interest(80 mm×80 mm×80 mm)at ranges of 95,105,190 and 290 mm.From patients who underwent carbon ion therapy at Shanghai Proton and Heavy Ion Center,20 cases were selected via simple random sampling with computer-generated random numbers,stratified by the proportion of different tumor sites(6 head and neck tumors,4 prostate tumors,4 lung tumors,2 pancreatic tumors,2 liver tumors and 2 shoulder tumors).Key dosimetric metrics,including homogeneity index(HI),conformity index(CI)and clinical target volume(CTV)coverage by 95%prescription dose(V95),were analyzed along with OAR doses.Energy layers,beam time,and irradiation time were compared between the two RiFi types.Statistical analysis was performed using the Wilcoxon rank-sum test,with a significance level of P＜0.05.This study was approved by the ethics committee of Shanghai Proton and Heavy Ion Center(approval number:240311EXP-01).Results:For water phantom plans,the 1D-RiFi plans achieved HI of 0.04±0.01,CI of 1.10±0.03,V95 of 99.92%±0.06%and flatness of 6.52%±0.61%,while the 2D-RiFi plans achieved HI of 0.04±0.01,CI of 1.11±0.04,V95 of 99.92%±0.06%,and flatness of 7.52%±0.81%.The mean doses to the distal and lateral block in 1D-RiFi plans were(1.34 Gy±0.43)Gy[relative biological effectiveness(RBE)]and(0.98±0.05)Gy(RBE),respectively,compared to(1.47±0.33)Gy(RBE)and(0.94±0.03)Gy(RBE)for 2D-RiFi plans.The use of 2D-RiFi reduced the average beam-on time by 43%and the number of energy layers by 48%.For clinical plans,the 1D-RiFi plans had HI of 0.07±0.04,CI of 1.94±0.67,and V95 of 98.81%±1.61%,compared to HI of 0.07±0.05,CI of 1.95±0.70,and V95 of 98.79%±1.69%for the 2D-RiFi plans,with no statistically significant differences(P=0.77,0.65 and 0.66,respectively).OAR mean doses increased slightly with the 2D-RiFi plans(average increase of 0.8%,P=0.62)but remained within clinically acceptable limits.The 2D-RiFi plans reduced energy layers by 45%-50%(average 48%),beam time by 32%-49%(average 44%),and irradiation time by 28%-41%(average 36%).Conclusion:Treatment plans using the 2D-RiFi achieved comparable target coverage to those using the 1D-RiFi,with a slight but clinically acceptable increase in OAR doses.The application of the 2D-RiFi significantly reduced the number of energy layers,beam time and irradiation time in carbon ion therapy,enhancing treatment efficiency.

Background and purpose:The ripple filter(RiFi)is a passive energy modulator used in particle beam therapy to broaden the Bragg peak.The 1D-RiFi features a wavy structure that can broaden a monoenergetic carbon ion beam to 3 mm,while the 2D-RiFi employs a two-dimensional groove structure to achieve a 6 mm beam broadening.This study aimed to evaluate the potential advantages of the 2D-RiFi over the 1D-RiFi in terms of dose distribution optimization,treatment efficiency,and organ at risk(OAR)dose control by comparing water phantom and clinical patient plans.Methods:Carbon ion treatment plans were designed for water phantoms and 20 patients using both 1D-RiFi and 2D-RiFi.The water phantom plans targeted a cubic region of interest(80 mm×80 mm×80 mm)at ranges of 95,105,190 and 290 mm.From patients who underwent carbon ion therapy at Shanghai Proton and Heavy Ion Center,20 cases were selected via simple random sampling with computer-generated random numbers,stratified by the proportion of different tumor sites(6 head and neck tumors,4 prostate tumors,4 lung tumors,2 pancreatic tumors,2 liver tumors and 2 shoulder tumors).Key dosimetric metrics,including homogeneity index(HI),conformity index(CI)and clinical target volume(CTV)coverage by 95%prescription dose(V95),were analyzed along with OAR doses.Energy layers,beam time,and irradiation time were compared between the two RiFi types.Statistical analysis was performed using the Wilcoxon rank-sum test,with a significance level of P＜0.05.This study was approved by the ethics committee of Shanghai Proton and Heavy Ion Center(approval number:240311EXP-01).Results:For water phantom plans,the 1D-RiFi plans achieved HI of 0.04±0.01,CI of 1.10±0.03,V95 of 99.92%±0.06%and flatness of 6.52%±0.61%,while the 2D-RiFi plans achieved HI of 0.04±0.01,CI of 1.11±0.04,V95 of 99.92%±0.06%,and flatness of 7.52%±0.81%.The mean doses to the distal and lateral block in 1D-RiFi plans were(1.34 Gy±0.43)Gy[relative biological effectiveness(RBE)]and(0.98±0.05)Gy(RBE),respectively,compared to(1.47±0.33)Gy(RBE)and(0.94±0.03)Gy(RBE)for 2D-RiFi plans.The use of 2D-RiFi reduced the average beam-on time by 43%and the number of energy layers by 48%.For clinical plans,the 1D-RiFi plans had HI of 0.07±0.04,CI of 1.94±0.67,and V95 of 98.81%±1.61%,compared to HI of 0.07±0.05,CI of 1.95±0.70,and V95 of 98.79%±1.69%for the 2D-RiFi plans,with no statistically significant differences(P=0.77,0.65 and 0.66,respectively).OAR mean doses increased slightly with the 2D-RiFi plans(average increase of 0.8%,P=0.62)but remained within clinically acceptable limits.The 2D-RiFi plans reduced energy layers by 45%-50%(average 48%),beam time by 32%-49%(average 44%),and irradiation time by 28%-41%(average 36%).Conclusion:Treatment plans using the 2D-RiFi achieved comparable target coverage to those using the 1D-RiFi,with a slight but clinically acceptable increase in OAR doses.The application of the 2D-RiFi significantly reduced the number of energy layers,beam time and irradiation time in carbon ion therapy,enhancing treatment efficiency.

Objective: To investigate a SARS-CoV-2 epidemic reported in Rongcheng City, Weihai, Shandong Province. Methods: The SARS-CoV-2 nucleic acid positive patients and their close contacts were investigated, and the whole genome sequencing and genetic evolution analysis of 9 variant viruses were carried out. An infection source investigation and analysis were carried out from two sources of home and abroad, and three aspects of human, material and environment. Results: A total of 15 asymptomatic infections were reported in this epidemic, including 13 cases as employees of workshop of aquatic products processing company, with an infection rate of 21.67% (13/60). Two cases were infected people's neighbors in the same village (conjugal relation). The first six positive persons were processing workers engaged in the first process of removing squid viscera in the workshop of the company. The nucleic acid Ct value of the first time were concentrated between 15 and 29, suggesting that the virus load was high, which was suspected to be caused by one-time homologous exposure. The whole genome sequence of 9 SARS-CoV-2 strains was highly homologous, belonging to VOC/Gamma (Lineage P.1.15). No highly homologous sequences were found from previous native and imported cases in China. It was highly homologous with the six virus sequences sampled from May 5 to 26, 2021 uploaded by Chile. The infection source investigation showed that the company had used the squid raw materials captured in the ocean near Chile and Argentina from May to June 2021 over the last 14 days. Many samples of raw materials, products and their outer packages in the inventory were tested positive for nucleic acid. Conclusion: This epidemic is the first local epidemic caused by the VOC/Gamma of SARS-CoV-2 in China. It is speculated that the VOC/Gamma, which was prevalent in South America from May to June 2021, could be imported into China through frozen squid.
Humans ; SARS-CoV-2 ; COVID-19 ; Epidemics ; China/epidemiology*

Macrolide antibiotics are a class of broad-spectrum antibiotics with the macrolide as core nucleus. Recently, antibiotic pollution has become an important environmental problem due to the irregular production and abuse of macrolide antibiotics. Microbial degradation is one of the most effective methods to deal with antibiotic pollution. This review summarizes the current status of environmental pollution caused by macrolide antibiotics, the degradation strains, the degradation enzymes, the degradation pathways and the microbial processes for degrading macrolide antibiotics. Moreover, the critical challenges on the biodegradation of macrolide antibiotics were also discussed.
Anti-Bacterial Agents ; Biodegradation, Environmental ; Macrolides

Objective:To assess the optimal cut-off value between early recurrence and late recurrence of patients with hepatocellular carcinoma (HCC) after radiofrequency ablation (RFA), and to construct a nomogram to predict early recurrence.Methods:A total of 119 patients with HCC who recurred after RFA in Cancer Hospital, Chinese Academy of Medical Sciences from January 2012 to December 2017 were identified. The optimal cut-off value to distinguish early and late recurrence was determined based on differences in post recurrence survival (PRS) by minimum P-value approach. The clinical and radiographic risk factors for early recurrence were identified by univariate and multivariate Logistic regression analysis. The predictive nomogram was constructed by these factors and internally validated. Results:The optimal cut-off value to distinguish early recurrence and late recurrence was 12 months after RFA ( P=0.005). The patients were divided into early recurrence group (47 cases) and late recurrence group (72 cases). The lower quartile PRS (Q1-PRS) and lower quartile overall survival (Q1-OS) were 11.1 and 19.1 months in the early recurrence group, which were shorter than 31.6 and 81.0 months in the late recurrence group ( P=0.005 and P<0.001, respectively). The independent risk factors of early recurrence were alpha fetoprotein (AFP) ( OR=8.459, 95% CI: 2.231-32.073), albumin(ALB) ( OR=0.251, 95% CI: 0.047-1.339), number of lesions ( OR=3.842, 95% CI: 1.424-10.365) and peritumoral enhancement ( OR=8.05, 95% CI: 1.23-52.80), which were further incorporated into constructing the predictive nomogram of early recurrence of HCC after RFA. Internal validation results showed the area under the curve, sensitivity, specificity of the receiver operating characteristic (ROC) curve were 0.839, 68.1% and 93.1%, respectively. The calibration curve showed the predicted curve of nomogram was close to the ideal curve. Hosmer-Lemeshow test showed there was no significant difference between the predicted results of nomogram and the actual results ( P=0.424). Conclusions:An interval of 12 months after RFA is the optimal cut-off value for defining early recurrence and late recurrence. The nomogram is integrated by clinical and radiographic features, which can potentially predict early recurrence of HCC after RFA and may offer useful guidance for individual treatment or follow up.

Objective:To assess the optimal cut-off value between early recurrence and late recurrence of patients with hepatocellular carcinoma (HCC) after radiofrequency ablation (RFA), and to construct a nomogram to predict early recurrence.Methods:A total of 119 patients with HCC who recurred after RFA in Cancer Hospital, Chinese Academy of Medical Sciences from January 2012 to December 2017 were identified. The optimal cut-off value to distinguish early and late recurrence was determined based on differences in post recurrence survival (PRS) by minimum P-value approach. The clinical and radiographic risk factors for early recurrence were identified by univariate and multivariate Logistic regression analysis. The predictive nomogram was constructed by these factors and internally validated. Results:The optimal cut-off value to distinguish early recurrence and late recurrence was 12 months after RFA ( P=0.005). The patients were divided into early recurrence group (47 cases) and late recurrence group (72 cases). The lower quartile PRS (Q1-PRS) and lower quartile overall survival (Q1-OS) were 11.1 and 19.1 months in the early recurrence group, which were shorter than 31.6 and 81.0 months in the late recurrence group ( P=0.005 and P<0.001, respectively). The independent risk factors of early recurrence were alpha fetoprotein (AFP) ( OR=8.459, 95% CI: 2.231-32.073), albumin(ALB) ( OR=0.251, 95% CI: 0.047-1.339), number of lesions ( OR=3.842, 95% CI: 1.424-10.365) and peritumoral enhancement ( OR=8.05, 95% CI: 1.23-52.80), which were further incorporated into constructing the predictive nomogram of early recurrence of HCC after RFA. Internal validation results showed the area under the curve, sensitivity, specificity of the receiver operating characteristic (ROC) curve were 0.839, 68.1% and 93.1%, respectively. The calibration curve showed the predicted curve of nomogram was close to the ideal curve. Hosmer-Lemeshow test showed there was no significant difference between the predicted results of nomogram and the actual results ( P=0.424). Conclusions:An interval of 12 months after RFA is the optimal cut-off value for defining early recurrence and late recurrence. The nomogram is integrated by clinical and radiographic features, which can potentially predict early recurrence of HCC after RFA and may offer useful guidance for individual treatment or follow up.

Objective To analyze the type-specific prevalence of human papillomavirus(HPV) among women aged 18-45 years from the general population in Liuzhou,Guangxi Zhuang Autonomous Region.Methods Totally,2 300 women aged 18-45 years old were enrolled in Liuzhou,from March to July,2013.Cervical exfoliated cells were collected for liquid based cytological and HPV DNA tests.Women were referred to colposcopy exam,based on the clinical practice guideline.Results Overall,the prevalence rates of any HPV or oncogenic HPV appeared as 22.7％ (95％CI:21.0％-24.4％) and 17.3％ (95％CI:16.0％-19.1％),respectively in this population under study.The high-risk HPV prevalence peaked at the age groups of 18-25 and 41-45,increasing along with the severity through cytological and histological tests.Statistically significant differences between the prevalence of CIN2 + (Cervical intraepithelial neoplasia 2 +) in women older than 26 years (1.7％,95％CI:1.0％-2.4％) and 18-25 years (1.2％,95％CI:0.5％-1.9％) of age,were not observed.Among samples diagnosed as CIN2+,positivity of HPV bivalent (16/18) and nine-valent (6/ 11/16/18/31/33/45/52/58) vaccine,related high risks on the types of HPV types appeared as 44.1％ and 97.1％.Conclusions The age-specific HPV prevalence rates in the general women aged 18-45 in Liuzhou presented as having bimodal distribution,suggesting that the disease burden of cervical diseases in women aged 26-45 years should not be ignored.Nine-valent HPV vaccine might provide more effective prevention outcomes on cervical cancer in China.

Objective: Heart failure (HF) patients are usually associated with liver function impairment, Child-Turcotte-Pugh (CTP) scores can evaluate liver function, but its effect in HF patients has been unclear. We want to study the application of CTP scores in predicting the risk of death for in-hospital HF patients. Methods: A total of 1180 consecutive in-hospital HF patients were enrolled. According to CTP scores evaluated liver function at admission, the patients were divided into 3 groups: CTP grade A group, n=951, CTP grade B group, n=206 and CTP grade C group, n=23. The endpoint of this study was all-cause death. Results: There were 180 patients died at 1 year follow-up period, the in-hospital and 1 year mortalities were increased with the elevated CTP grades accordingly: for in-hospital mortalities in CTP grade A, B and C groups were (0.8%, 11.7% and 56.5%) respectively, P< 0.001; for 1 year mortalities were (9.6%, 34.5% and 78.3%) respectively, P< 0.001. Multivariable Cox regression analyses indicated that the higher CTP grades, the higher risk of in-hospital and 1 year mortalities in HF patients. The area under curve for CTP scores in predicting the in-hospital and 1 year mortalities were 0.88 and 0.74 respectively. Kaplan-Meier survival analysis presented that the patients with improved CTP scores from grade B or C to grade A at discharge had the higher 1 year survival rate than those without improvement, P=0.028.
Conclusion: CTP scores may independently predict the risk of death for in-hospital HF patients, the levels of CTP scores might be used for evaluating the efficacy of in-hospital treatment.

Objective To investigate the association between chronic kidney dysfunction and the complexity of coronary artery disease in elderly patients.Methods A prospective study was conducted on 1380 consecutive patients underwent coronary angiography for the first time in our hospital and with angiographically diagnosed coronary artery disease from January 2011 to June 2012.The complexity of coronary artery disease were classified according to the American College of Cardiology/American Heart Association (ACC/AHA) grading system as types A,B1,B2,and C.Estimated glomerular filtration rate (eGFR) was calculated by the simplified Modification of Diet in Renal Disease(MDRD)equation.Patients were classified into 3 stages according to eGFR as follows:normal renalfunction(n=234,eGFR≥90 ml· min-1 · 1.73 m-2),mild renaldysfunction(n=881,60≤eGFR＜90 ml · min-1 · 1.73 m-2,and moderate or severe renaldysfunction(n=265,eGFR＜60ml · min-1 · 1.73 m-2).Ordinal logistic regression was used to analyze the association between chronic kidney dysfunction and the complexity of coronary artery disease.Results Patients with mild,moderate or severe renal dysfunction were older (F=56.82,P＜0.001),more predominantly female (x2 =66.29,P＜ 0.001) and more likely to have history of hypertension (x2 =17.57,P ＜ 0.001),diabetes (x2=20.97,P＜0.001) and hyperlipidemia (x2=10.48,P 0.005) than those with normal renal function.The percentage of lesions of types B2 or C in moderate or severe renal dysfunction group was higher than that in normal renal function group (x2=175.03,P＜0.001).The ordinal logistic regression showed that age,male,hypertension,diabetes,C-reactive protein and eGFR were independent risk factors for the ACC/AHA lesion classification.Conclusions Age,male,hypertension,diabetes,C-reactive protein and eGFR are independent risk factors for the complexity of coronary artery disease.

Objective To evaluate the immunogenicity of a Haemophilus influenzae type b capsular-tetanus toxoid(Hib-TT) conjugate vaccine produced by Lanzhou Institute of Biological products(LIBP).Methods In an open-controlled,randomized trial,the eligible and consented 6-59 months-old young children injected 2 or 1 times 1 month apart with Hib-TT conjugate vaccine,the 3-5 months-old infants received 3 injections 1 month apart for primary immunization with Hib-TT or a licensed international Hib-TT conjugate vaccine as the control vaccine,and the boosting dose of two 3-5 months-old groups was injected at the 15-17months-old.The serum anti-Hib PRP IgG GMC in both groups after primary and boosting vaccination was measured by ELISA,the percentage of geometric mean concentration (GMC) ≥ 0.15 μg/ml and ≥ 1.0μg/ml was calculated,respectively.Results The Hib-TT conjugate vaccine produced in LIBP elicited satisfactory IgG antibody response in 3-59 months-old young children,the serum IgG GMC of anti-Hib PRP were 14.52 μg/ml(95％ CI:12.31-17.14)in 3-5 months-old,14.04 μg/ml(95％ CI:12.40-15.90) in 6-11 months-old.the ratios of IgG antibody concentration ≥ 1.0 μg/ml were 96.90％ (95％ CI:92.50-99.20) in study vaccine group and 98.55％ (95％ CI:92.20-99.90) in the control vaccine after 3 doses,respectively.100％ of the 6-11 months-old young children who injected 2 times with the Hib-TT conjugate vaccine had IgG antibody concentration ≥ 1.0 μg/ml (95％ CI:95.94-100.00),91.35％ (95％ CI:86.13-99.48) of recipients in 12-59 months-old young children induced the IgG antibody concentration ≥ 1.0 μg/ml after a single dose.The serum IgG antibody GMC in recipients who received the study or and control vaccines increased from 6.27 μg/ml (95 ％ CI:5.28-7.48) and 5.57 μg/ml (95 ％ CI:4.45-6.97)at pre-boosting injections to 63.14 μg/ml(95％ CI:52.14-76.47) and 73.48 μg/ml (95％ CI:57.37-94.11) one month after boosting injection,respectively.The percentage of IgG antibody concentration ≥ 1.0 μg/ml increased from 76.35％ and 79.55％ of pre-boosting to 100％ in the two groups after booting dose.Although the serum IgG GMC in two groups appeared to decline markedly,it remained at a relatively high levels of 25.02 μg/ml (95％ CI:20.51-30.48) in the study vaccine and 23.64 μg/ml (95％ CI:18.40-30.43) in the control vaccine,and all of the recipients in both groups remained 100.0％ of IgG antibody concentration ≥ 1.0 μg/ml.Conclusion The study vaccine elicited a protective immune response and induced the IgG antibody concentration which indicated long-term protection of anti-Hib PRP in 3 to 59months-old infants and young children.