OBJECTIVE To investigate the regulatory effects of tofacitinib combined with methotrexate （MTX） on gut microbiota and the clinical efficacy of this regimen in patients with rheumatoid arthritis （RA）. METHODS A retrospective analysis was conducted on the clinical data of 182 patients with RA admitted to Xingtai People’s Hospital from January 2022 to June 2025. The patients were divided into a control group （ n ＝88， treated with MTX monotherapy） and an observation group （ n ＝94， treated with tofacitinib combined w ith MTX） based on their treatment regimen. Gut microbiota abundance， inflammatory and immunological indicators [C-reactive protein （CRP）， erythrocyte sedimentation rate （ESR）， rheumatoid factor （RF）， and anti-cyclic citrullinated peptide antibody （anti-CCP） ] ， clinical efficacy indicators [American College of Rheumatology 20% response rate （ACR20）， Disease Activity Score in 28 Joints （DAS28）， and Health Assessment Questionnaire （HAQ） score ] ， and adverse reactions during treatment were compared between the two groups before and after 12 weeks of treatment. RESULTS After treatment， the abundance of Lactobacillus and Bifidobacterium were significantly increased in both groups compared with before treatment， whereas the abundances of Enterococcus and Enterobacter ， as well as the levels of CRP， ESR， RF， anti-CCP， DAS28 score， and HAQ score， were significantly decreased （ P ＜0.05）. The degree of improvement in the observation group was significantly greater than that in the control group （ P ＜0.05）. The ACR20 response rate in the observation group was significantly higher than that in the control group （81.91% vs. 56.82%， P ＜0.05）. There was no statistically significant difference in the incidence of adverse reactions between the two groups （ P ＞0.05）， and the main adverse reactions were gastrointestinal reactions and abnormal liver function. CONCLUSIONS Tofacitinib combined with MTX can effectively improve gut microbiota balance in patients with RA by increasing the abundance of probiotics and reducing the abundance of opportunistic pathogenic bacteria， thereby improving immune and inflammatory status. In addition， this combination regimen can enhance clinical efficacy， reduce disease activity， and improve functional status， with a favorable safety profile.

Objective:To evaluate the cumulative relationship between individual cardiometabolic diseases(CMDs)and the incidence of cataract in the elderly.Methods:This study was a prospective cohort study based on the UK Biobank, including 165 222 participants without cataract at baseline, aged 60.0 to 74.0 years, with an average age of(64.9±2.9)years, including 76 712 males(46.4%)and 88 510 females(53.6%). The exposure in this study was CMDs(including coronary heart disease, stroke, diabetes, and hypertension), and the outcome was the incidence of cataract.The Cox proportional hazards model was used to evaluate the cumulative hazard ratio( HR)and 95% confidence interval( CI)of the number of CMDs and cataract occurrence in the elderly. Results:After a median follow-up of 13.65 years, 35, 933 cataract events were observed.After adjusting for various factors, the HRs of cataract incidence in elderly patients with 1, 2, and 3 or more CMDs compared with those without CMDs were 1.11( HR=1.11, 95% CI: 1.08~1.14, P<0.001), 1.38( HR=1.38, 95% CI: 1.33~1.43, P<0.001), and 1.80( HR=1.80, 95% CI: 1.68-1.93, P<0.001), respectively.There was a significant dose-cumulative effect between the number of CMDs and the risk of cataract( HR=1.17, 95% CI: 1.15~1.19, P<0.001). Conclusions:The coexistence of CMDs in the elderly is an important risk factor for cataract development, and the risk of cataract increases in a dose-cumulative manner with the increase in the number of CMDs, suggesting that emphasizing health management of CMDs in the elderly population may help reduce the incidence of cataract.

Objective:To evaluate the cumulative relationship between individual cardiometabolic diseases(CMDs)and the incidence of cataract in the elderly.Methods:This study was a prospective cohort study based on the UK Biobank, including 165 222 participants without cataract at baseline, aged 60.0 to 74.0 years, with an average age of(64.9±2.9)years, including 76 712 males(46.4%)and 88 510 females(53.6%). The exposure in this study was CMDs(including coronary heart disease, stroke, diabetes, and hypertension), and the outcome was the incidence of cataract.The Cox proportional hazards model was used to evaluate the cumulative hazard ratio( HR)and 95% confidence interval( CI)of the number of CMDs and cataract occurrence in the elderly. Results:After a median follow-up of 13.65 years, 35, 933 cataract events were observed.After adjusting for various factors, the HRs of cataract incidence in elderly patients with 1, 2, and 3 or more CMDs compared with those without CMDs were 1.11( HR=1.11, 95% CI: 1.08~1.14, P<0.001), 1.38( HR=1.38, 95% CI: 1.33~1.43, P<0.001), and 1.80( HR=1.80, 95% CI: 1.68-1.93, P<0.001), respectively.There was a significant dose-cumulative effect between the number of CMDs and the risk of cataract( HR=1.17, 95% CI: 1.15~1.19, P<0.001). Conclusions:The coexistence of CMDs in the elderly is an important risk factor for cataract development, and the risk of cataract increases in a dose-cumulative manner with the increase in the number of CMDs, suggesting that emphasizing health management of CMDs in the elderly population may help reduce the incidence of cataract.

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 explore effects of tofacitinib combined with traditional disease modifying antirheumatic drugs(DMARDs)on peripheral blood IL-22,IL-23 and Th22 cell subsets in patients with rheumatoid arthritis(RA).Methods:Retrospec-tive analysis of clinical data of 100 RA patients admitted to Xingtai People's Hospital from December 2022 to December 2024.Patients were divided into conventional group(n=33,treated with traditional DMARDs),single group(n=34,treated with tofacitinib)and combination group(n=33,treated with tofacitinib combined with traditional DMARDs)by random number table method.Serum IL-22 and IL-23 levels,Th22 cell subsets proportion,recovery of joint function,disease improvement and adverse reactions were compared in three group.Results:After 3 months of treatment,IL-22,IL-23 and Th22 cell subsets proportion in three groups were decreased compared to before treatment,and combination group was significantly lower than conventional group and single group(P<0.05);levels of anti-CCP and RF in three groups were decreased compared to before treatment,and combined group was significantly lower than conventional group and single group(P<0.05);joint swelling frequency,number of tender joints,morning stiffness time and VAS scores in three groups were decreased compared to before treatment,and combination group was significantly lower than conven-tional group and single group(P<0.05);DAS28 scores and HAQ scores of three groups were decreased compared to before treatment,and combined group was significantly lower than conventional group and single group(P<0.05);there was no statistically significant difference in incidence of adverse reactions among three groups during treatment period(Z=0.290,P=0.865).Conclusion:Clinical effect of tofacitinib combined with traditional DMARDs in treatment of RA is significant,which can effectively reduce serum IL-22,IL-23 and autoantibodies levels,regulate Th22 cell subsets proportion,alleviate inflammatory reactions,and improve joint function.

Objective:To explore the accuracy of in-room on-rails CT (IRCT) for image-guided radiotherapy (IGRT) and adaptive radiotherapy (ART) during proton and heavy-ion radiotherapy.Methods:The positioning accuracy and registration accuracy of IRCT were tested by using the spherical phantom and multiple imaging modality iso-centricity, and the positioning accuracy of isocenter geometric mapping and 3D-3D registration accuracy were evaluated when the phantoms were applied to IGRT. Standard water-aluminum phantom and ACR467 phantom were utilized to establish and evaluate the HU value-relative linear stopping power to water (RLSP) conversion curve. By scanning the same rigid phantom images on both IRCT and planned CT, followed by dose calculation and comparison of dose differences, the consistency of dose distribution between 2 modalities was evaluated when applied to ART in relation to the planned CT. Pre-treatment CT of patient was acquired using IRCT scan before treatment. Online qualitative analysis and offline quantitative analysis were performed. A case of prostate cancer was selected, and its online qualitative analysis ability was tested by evaluating whether IRCT could effectively identify changes in the position of clinical target volume (CTV) and critical organs at risk. One case of prostate cancer and 1 case of breast cancer were selected, and the offline quantitative analysis ability was tested by the key dose volume histogram parameters of dose recalculation on CT before treatment.Results:In IGRT application, the isocenter geometric mapping positioning accuracy was 0.1 mm. The displacement accuracy for 3D-3D registration was 0.8 mm, with a rotational accuracy of 0.6°. In ART application, a CT HU value-RLSP conversion curve was established using standard methods. The RLSP variation range for 24 representative tissues was -3.91% to 1.49%, with an average variation of -0.75%±0.95%. Calculation results performed on rigid phantoms for head, chest, and abdominal-pelvic regions showed that compared to the planned CT, the γ pass rate for proton plan dose distribution consistency on IRCT was>97%, and >95% for carbon-ion plan, both using 2%/2 mm criteria with a 10% threshold. The results of 2 representative clinical applications showed that online qualitative analysis of carbon-ion plans for prostate cancer could identify changes in patient soft tissue position relative to the planned CT, CTV, and critical organs at risk before treatment. Offline quantitative analysis could quantify dose changes in patients undergoing treatment. In the prostate cancer original plan for prostate cancer, the relative volume of CTV receiving 95% (V 95%) of the prescribed dose was 100%, which were 97.63% and 99.91% before different fractions of treatment, respectively. For the bladder and rectum, V 95% was 3.00% and 3.80%, which were changed to 0.75% and 12.36% for one session of treatment, and 2.76% and 3.08% for another session of treatment, aligning with the results of online qualitative analysis. In the original plan for breast cancer, tumor bed CTV and breast CTV V 95% were 99.93% and 99.93%, which were 100.00% and 99.57% for one session of treatment and 92.32% and 93.13% for another session of treatment, triggering re-planning. The re-planned results were improved to 99.82% and 99.93%. Conclusions:IRCT can be applied to IGRT and ART in proton and heavy-ion radiotherapy, enabling accurate patient positioning verification and adjustment, as well as online anatomical qualitative analysis and offline dose quantitative analysis.

Objective:To compare the effects of standard cognitive behavioral therapy for insomnia (CBT-I) and enhanced cognitive behavioral therapy for insomnia(CBT-I Plus) in patients with chronic insomnia disorder comorbid anxiety or depressive symptoms.Methods:This prospective study included 148 patients with chronic insomnia disorder and anxiety/depression symptoms who were treated at the Sleep Disorder clinic of Shanghai Mental Health Center between July 2020 and August 2023. Participants (56 males, 92 females; aged 18-65 years, mean age 35.08±10.30 years) were randomly assigned in a 1∶2 ratio to the CBT-I group ( n=54) or CBT-I Plus group ( n=94). The CBT-I Plus group received additional treatments targeting anxiety and depressive symptoms. Treatment lasted 8 weeks, with assessment conducted at baseline, weeks 2, 4, and 8. Depression severity was measured using the 17-item Hamilton Depression Rating Scale (HAMD 17), anxiety severity with the Hamilton Anxiety Scale (HAMA), and sleep quality with the Pittsburgh Sleep Quality Index (PSQI). Paired sample t-tests were used to evaluate within-group changes, repeated-measures ANOVA compared treatment effects between groups, and ANCOVA was employed to adjust for confounding variables. Results:Significant reductions in PSQI, HAMD 17, and HAMA scores were observed in both groups after treatment: CBT-I group: PSQI ((14.15±2.54) vs. (7.50±3.35), t=13.25), HAMD 17 ((14.70±4.09) vs. (7.40±4.61), t=9.33), and HAMA ((14.94±4.11) vs. (5.56±3.67), t=12.38) (all P<0.001).CBT-I Plus group: PSQI ((14.87±3.01) vs. (7.19±3.86), t=18.75), HAMD 17 ((16.84±3.91) vs. (6.84±4.79), t=17.42), and HAMA ((15.57±3.93) vs. (6.10±4.57), t=18.39) (all P<0.001). After adjusting for HAMD 17 scores and medication use, no statistically significant between-group differences were observed in changes in PSQI, HAMD 17, and HAMA scores ( P>0.05). A significant time-by-group interaction was found for the PSQI daytime dysfunction subscale ( F=4.87, P<0.01). Conclusion:Both CBT-I and CBT-I Plus improve sleep and emotional symptoms in patients with chronic insomnia disorder and comorbid anxiety/depression symptoms. However, CBT-I Plus has no significant advantages over standard CBT-I. Further studies are needed to refine the timing and content of interventions.

Objective:To explore the accuracy of in-room on-rails CT (IRCT) for image-guided radiotherapy (IGRT) and adaptive radiotherapy (ART) during proton and heavy-ion radiotherapy.Methods:The positioning accuracy and registration accuracy of IRCT were tested by using the spherical phantom and multiple imaging modality iso-centricity, and the positioning accuracy of isocenter geometric mapping and 3D-3D registration accuracy were evaluated when the phantoms were applied to IGRT. Standard water-aluminum phantom and ACR467 phantom were utilized to establish and evaluate the HU value-relative linear stopping power to water (RLSP) conversion curve. By scanning the same rigid phantom images on both IRCT and planned CT, followed by dose calculation and comparison of dose differences, the consistency of dose distribution between 2 modalities was evaluated when applied to ART in relation to the planned CT. Pre-treatment CT of patient was acquired using IRCT scan before treatment. Online qualitative analysis and offline quantitative analysis were performed. A case of prostate cancer was selected, and its online qualitative analysis ability was tested by evaluating whether IRCT could effectively identify changes in the position of clinical target volume (CTV) and critical organs at risk. One case of prostate cancer and 1 case of breast cancer were selected, and the offline quantitative analysis ability was tested by the key dose volume histogram parameters of dose recalculation on CT before treatment.Results:In IGRT application, the isocenter geometric mapping positioning accuracy was 0.1 mm. The displacement accuracy for 3D-3D registration was 0.8 mm, with a rotational accuracy of 0.6°. In ART application, a CT HU value-RLSP conversion curve was established using standard methods. The RLSP variation range for 24 representative tissues was -3.91% to 1.49%, with an average variation of -0.75%±0.95%. Calculation results performed on rigid phantoms for head, chest, and abdominal-pelvic regions showed that compared to the planned CT, the γ pass rate for proton plan dose distribution consistency on IRCT was>97%, and >95% for carbon-ion plan, both using 2%/2 mm criteria with a 10% threshold. The results of 2 representative clinical applications showed that online qualitative analysis of carbon-ion plans for prostate cancer could identify changes in patient soft tissue position relative to the planned CT, CTV, and critical organs at risk before treatment. Offline quantitative analysis could quantify dose changes in patients undergoing treatment. In the prostate cancer original plan for prostate cancer, the relative volume of CTV receiving 95% (V 95%) of the prescribed dose was 100%, which were 97.63% and 99.91% before different fractions of treatment, respectively. For the bladder and rectum, V 95% was 3.00% and 3.80%, which were changed to 0.75% and 12.36% for one session of treatment, and 2.76% and 3.08% for another session of treatment, aligning with the results of online qualitative analysis. In the original plan for breast cancer, tumor bed CTV and breast CTV V 95% were 99.93% and 99.93%, which were 100.00% and 99.57% for one session of treatment and 92.32% and 93.13% for another session of treatment, triggering re-planning. The re-planned results were improved to 99.82% and 99.93%. Conclusions:IRCT can be applied to IGRT and ART in proton and heavy-ion radiotherapy, enabling accurate patient positioning verification and adjustment, as well as online anatomical qualitative analysis and offline dose quantitative analysis.

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 explore effects of tofacitinib combined with traditional disease modifying antirheumatic drugs(DMARDs)on peripheral blood IL-22,IL-23 and Th22 cell subsets in patients with rheumatoid arthritis(RA).Methods:Retrospec-tive analysis of clinical data of 100 RA patients admitted to Xingtai People's Hospital from December 2022 to December 2024.Patients were divided into conventional group(n=33,treated with traditional DMARDs),single group(n=34,treated with tofacitinib)and combination group(n=33,treated with tofacitinib combined with traditional DMARDs)by random number table method.Serum IL-22 and IL-23 levels,Th22 cell subsets proportion,recovery of joint function,disease improvement and adverse reactions were compared in three group.Results:After 3 months of treatment,IL-22,IL-23 and Th22 cell subsets proportion in three groups were decreased compared to before treatment,and combination group was significantly lower than conventional group and single group(P<0.05);levels of anti-CCP and RF in three groups were decreased compared to before treatment,and combined group was significantly lower than conventional group and single group(P<0.05);joint swelling frequency,number of tender joints,morning stiffness time and VAS scores in three groups were decreased compared to before treatment,and combination group was significantly lower than conven-tional group and single group(P<0.05);DAS28 scores and HAQ scores of three groups were decreased compared to before treatment,and combined group was significantly lower than conventional group and single group(P<0.05);there was no statistically significant difference in incidence of adverse reactions among three groups during treatment period(Z=0.290,P=0.865).Conclusion:Clinical effect of tofacitinib combined with traditional DMARDs in treatment of RA is significant,which can effectively reduce serum IL-22,IL-23 and autoantibodies levels,regulate Th22 cell subsets proportion,alleviate inflammatory reactions,and improve joint function.