Objectives:To explore whether short-course radiotherapy (SCRT)-based total neoadjuvant therapy (TNT) combined with PD-1 inhibitors could further promote tumor regression and improve the prognosis.Methods:This is a prospective, multicenter, two-arm randomized controlled, seamless phase Ⅱ/Ⅲ trial for proficient mismatch repair or microsatellite stable (pMMR/MSS) locally advanced rectal cancer (LARC). Eligible patients were randomly assigned to the iTNT (TNT+PD-1) group or the TNT group. Patients in the TNT group received SCRT (5 Gy×5) followed by 4 cycles of CAPOX or 6 cycles of mFOLFOX chemotherapy, with the iTNT group receiving SCRT followed by the same regime in combination with 4 cycles of Sintilimab. Total mesorectal excision (TME) surgery or watch and wait (W&W) was performed after neoadjuvant therapy and then 2 cycles of same regimen as before were recommended. The primary endpoints are the complete response (CR) rate for phase Ⅱ trial and 3-year disease-free survival (DFS) for phase Ⅲ trial. A total of 588 patients will be enrolled for the phase Ⅱ/Ⅲ trial. Short-term efficacy and safety data from the initial 100 treated patients were analyzed as planned.Results:From 2022-8-31 to 2023-5-24 the initial 100 patients were enrolled from 10 hospitals in China, 76.0%(76/100) patients were male, and the median age was 61 years (21-74 years). More patients had tumors located in the lower rectum (78.0%, 78/100), staged T3-4 (97.0%, 97/100) and N1-2 (93.0%, 93/100), and about half of the tumors invaded the mesorectal fascia (52.0%, 52/100) and with extramural vascular invasion (51.0%, 51/100). Analyses were performed according to the per-protocal (PP) set. All patients in the iTNT group ( n=52) and the TNT group ( n=48) completed SCRT; The 4-cycle chemotherapy±Sintilimab completion rates were 86.5% and 100.0% in the iTNT and TNT groups, respectively. In the iTNT group, 82.7% (43/52), 11.5% (6/52), and 5.8% (3/52) of the patients received 4, 3, and 2 cycles of PD-1 inhibitor. After TNT, 68 patients underwent radical surgery and 15 patients achieved cCR and adopted W&W. The pathological complete response (pCR) rates were 48.5% (16/33) and 17.1% (6/35) in the iTNT and TNT groups, with CR rates of 50.0% (25/50) and 26.1% (12/46), respectively. The incidence of treatment-related grade 3-4 adverse events was 26.9% (14/52, iTNT group) and 18.8% (9/48, TNT group), with thrombocytopenia and leukopenia being the most common. Among patients receiving immunotherapy, grade 3 immunotherapy-related adverse events occurred in 2 (3.8%, 2/52) patients: one case was pancreatitis, another case was hepatitis combined with myositis and myocarditis. Conclusion:The preliminary results show that SCRT-based TNT combined with PD-1 inhibitors could further improve the CR rate for LARC without unexpected serious adverse events.

Objective To investigate the correlation between WT1,BCR-ABL genes and interleukin-6(IL-6),vascular endothelial growth factor(VEGF),plasma protein C(PC),plasma protein S(PS)in patients with myeloproliferative neoplasms(MPN).Methods A total of 54 MPN patients treated in this hospital from January 2021 to January 2024 were selected as the MPN group,and 54 healthy subjects undergoing physical examination during the same period were selected as the control group.The gene relative expression levels of WT1,BCR-ABL and levels of IL-6,VEGF,PC,and PS were detected and compared between the two groups.The correlations between WT1,BCR-ABL gene relative expression levels and IL-6,VEGF,PC,PS levels were analyzed,and the diagnostic efficacy of WT1 and BCR-ABL genes for MPN was evaluated by receiver operat-ing characteristic(ROC)curve.Results Compared with the control group,the gene relative expression levels of WT1,BCR-ABL and the levels of IL-6 and VEGF in the MPN group were higher,while the levels of PC and PS were lower,with statistically significant differences(P<0.05).Pearson correlation analysis showed that WT1 and BCR-ABL gene relative expression levels were positively correlated with IL-6 and VEGF levels,and negatively correlated with PC and PS levels(P<0.05).The combined use of WT1 and BCR-ABL genes has higher diagnostic efficacy for MPN than single indicators,with an area under the curve(AUC)of 0.833 and a sensitivity of 88.69%.Conclusion The relative expression levels of WT1 and BCR-ABL genes are correlated with IL-6,VEGF,PC,and PS levels in MPN patients.The combination of WT1 and BCR-ABL genes can effec-tively diagnose MPN.

Objectives:To explore whether short-course radiotherapy (SCRT)-based total neoadjuvant therapy (TNT) combined with PD-1 inhibitors could further promote tumor regression and improve the prognosis.Methods:This is a prospective, multicenter, two-arm randomized controlled, seamless phase Ⅱ/Ⅲ trial for proficient mismatch repair or microsatellite stable (pMMR/MSS) locally advanced rectal cancer (LARC). Eligible patients were randomly assigned to the iTNT (TNT+PD-1) group or the TNT group. Patients in the TNT group received SCRT (5 Gy×5) followed by 4 cycles of CAPOX or 6 cycles of mFOLFOX chemotherapy, with the iTNT group receiving SCRT followed by the same regime in combination with 4 cycles of Sintilimab. Total mesorectal excision (TME) surgery or watch and wait (W&W) was performed after neoadjuvant therapy and then 2 cycles of same regimen as before were recommended. The primary endpoints are the complete response (CR) rate for phase Ⅱ trial and 3-year disease-free survival (DFS) for phase Ⅲ trial. A total of 588 patients will be enrolled for the phase Ⅱ/Ⅲ trial. Short-term efficacy and safety data from the initial 100 treated patients were analyzed as planned.Results:From 2022-8-31 to 2023-5-24 the initial 100 patients were enrolled from 10 hospitals in China, 76.0%(76/100) patients were male, and the median age was 61 years (21-74 years). More patients had tumors located in the lower rectum (78.0%, 78/100), staged T3-4 (97.0%, 97/100) and N1-2 (93.0%, 93/100), and about half of the tumors invaded the mesorectal fascia (52.0%, 52/100) and with extramural vascular invasion (51.0%, 51/100). Analyses were performed according to the per-protocal (PP) set. All patients in the iTNT group ( n=52) and the TNT group ( n=48) completed SCRT; The 4-cycle chemotherapy±Sintilimab completion rates were 86.5% and 100.0% in the iTNT and TNT groups, respectively. In the iTNT group, 82.7% (43/52), 11.5% (6/52), and 5.8% (3/52) of the patients received 4, 3, and 2 cycles of PD-1 inhibitor. After TNT, 68 patients underwent radical surgery and 15 patients achieved cCR and adopted W&W. The pathological complete response (pCR) rates were 48.5% (16/33) and 17.1% (6/35) in the iTNT and TNT groups, with CR rates of 50.0% (25/50) and 26.1% (12/46), respectively. The incidence of treatment-related grade 3-4 adverse events was 26.9% (14/52, iTNT group) and 18.8% (9/48, TNT group), with thrombocytopenia and leukopenia being the most common. Among patients receiving immunotherapy, grade 3 immunotherapy-related adverse events occurred in 2 (3.8%, 2/52) patients: one case was pancreatitis, another case was hepatitis combined with myositis and myocarditis. Conclusion:The preliminary results show that SCRT-based TNT combined with PD-1 inhibitors could further improve the CR rate for LARC without unexpected serious adverse events.

Neoadjuvant therapy for locally advanced colorectal cancer has made great progress in the past 20 years, but there are still limitations such as side effects, organ dysfunction and unsatisfactory control of metastasis. In recent years, with the improvement of surgical techniques and further development of molecular research, how to further improve local control, reduce distant metastasis, and even avoid surgery according to clinical remission to achieve organ preservation, is the current demand and research goal. With the advancement of molecular research, colorectal cancer has different treatment strategies based on microsatellite status. For patients with microsatellite instability locally advanced colorectal cancer, immune checkpoint inhibitor therapy significantly increased the pathologic complete response rate, reduced the incidence of adverse events and improved organ function compared with conventional chemoradiotherapy. For patients with microsatellite stable locally advanced colon cancer, neoadjuvant therapy is still in the exploratory stage. The standard of care is surgery combined with perioperative chemotherapy. For microsatellite stable locally advanced rectal cancer, the complete response rate is improved by enhancing neoadjuvant therapy, which helps to preserve organs. On the other hand, selective radiotherapy preserves organ function and improves quality of life. This article reviews the neoadjuvant treatment strategies for locally advanced colorectal cancer based on organ-sparing strategies.

Neoadjuvant therapy for locally advanced colorectal cancer has made great progress in the past 20 years, but there are still limitations such as side effects, organ dysfunction and unsatisfactory control of metastasis. In recent years, with the improvement of surgical techniques and further development of molecular research, how to further improve local control, reduce distant metastasis, and even avoid surgery according to clinical remission to achieve organ preservation, is the current demand and research goal. With the advancement of molecular research, colorectal cancer has different treatment strategies based on microsatellite status. For patients with microsatellite instability locally advanced colorectal cancer, immune checkpoint inhibitor therapy significantly increased the pathologic complete response rate, reduced the incidence of adverse events and improved organ function compared with conventional chemoradiotherapy. For patients with microsatellite stable locally advanced colon cancer, neoadjuvant therapy is still in the exploratory stage. The standard of care is surgery combined with perioperative chemotherapy. For microsatellite stable locally advanced rectal cancer, the complete response rate is improved by enhancing neoadjuvant therapy, which helps to preserve organs. On the other hand, selective radiotherapy preserves organ function and improves quality of life. This article reviews the neoadjuvant treatment strategies for locally advanced colorectal cancer based on organ-sparing strategies.

Articular cartilage (AC) injuries often lead to cartilage degeneration and may ultimately result in osteoarthritis (OA) due to the limited self-repair ability. To date, numerous intra-articular delivery systems carrying various therapeutic agents have been developed to improve therapeutic localization and retention, optimize controlled drug release profiles and target different pathological processes. Due to the complex and multifactorial characteristics of cartilage injury pathology and heterogeneity of the cartilage structure deposited within a dense matrix, delivery systems loaded with a single therapeutic agent are hindered from reaching multiple targets in a spatiotemporal matched manner and thus fail to mimic the natural processes of biosynthesis, compromising the goal of full cartilage regeneration. Emerging evidence highlights the importance of sequential delivery strategies targeting multiple pathological processes. In this review, we first summarize the current status and progress achieved in single-drug delivery strategies for the treatment of AC diseases. Subsequently, we focus mainly on advances in multiple drug delivery applications, including sequential release formulations targeting various pathological processes, synergistic targeting of the same pathological process, the spatial distribution in multiple tissues, and heterogeneous regeneration. We hope that this review will inspire the rational design of intra-articular drug delivery systems (DDSs) in the future.

Objective:To summarize the levels of individual dose to radiation workers in Shandong province from 2016 to 2020, and to analyze the trends in their change in order to provide scientific basis for radiation workers′ health management.Methods:The experimental detection and quality control were carried out in compliance with the national standards Specifications for individual monitoring of occupational external exposure (GBZ 128-2019) and the Testing criteria of personnel dosimetry performance for external exposure (GBZ 207-2016). The result of the personal dose monitoring of occupational external exposure of all radiation workers monitored by the Centers for Disease Control and Prevention in 16 cities of Shandong province were retrospectively analyzed by using SPSS 23.0 software.Results:The total number of monitored workers were 25 523 with an average annual individual effective dose of 0.28 mSv. There were statistically significant differences among radiation workers in different years ( H= 2 815.91, P<0. 001). The average annual individual effective dose showed an upward trend followed by a downward trend. The average annual effective dose of 0.55 mSv for nuclear medicine radiation workers in medical applications was the highest, with statistically significant differences among different occupational radiation workers ( H=310.37, P<0.001). The average annual effective dose of 0.37 mSv for radioactivity logging workers in industrial applications was the highest, with statistically significant differences among different occupational radiation workers ( H=448.07, P<0. 001). The average annual effective dose to radiation workers in medical applications was higher than in industrial applications ( Z = -14.93, P<0.001). Conclusions:The average annual effective dose to nuclear medicine radiation workers in medical applications and logging radiation workers in industrial applications are relatively high. There would be a push to furthe improve workplace protection measures and strengthen the management and supervision of radiological workers.

Objective:To analyze the demands of contracted family doctor service among uncontracted young and middle-aged people in Shanghai Baoshan.Methods:An online questionnaire survey on demands of contracted family doctor service was conducted in June 2021 among 702 uncontracted residents aged 18-60 years from Shanghai Baoshan district selected by stratified random sampling method. The demands of contracted family doctor service, including digital health file, routine laboratory tests and imaging investigation;health promotion;service convenience; home service were surveyed, and the factors related the demands were analyzed with regression analysis.Results:The survey showed that the demands of service convenience (3.8(3.0, 5.0)) and home service (4.0(3.0, 5.0)) were higher, while those of digital health file (3.0(2.0, 5.0)) and health promotion (3.0(2.0, 5.0)) were relatively lower. There were significant differences in the demands of all five contracted services among residents with different gender, age, education level, household register and family income (all P<0.05); while for young residents with different types of medical insurance there was significant difference in demands of all contracted services except digital health file (all P<0.05). Logistic regression analysis indicated that female( OR=1.83, P<0.001), high educational level( OR=4.81, P=0.019), household registered in Shanghai( OR=1.80, P=0.004)had higher demand for service convenience; female gender( OR=1.68, P=0.001), high educational level( OR=4.56, P=0.023)had higher demand for home service demands. Conclusion:The demands for contracted family doctor services are different among the uncontracted young and middle-aged people in Baoshan district, while the service convenience is generally most demanded. The study indicates that the contracted family doctor service should be provided accordingly.

OBJECTIVE: To explore the genetic basis for a Chinese pedigree affected with hereditary spastic paraplegia type 30 (HSP30). METHODS: A proband presented at the Second Hospital of Shanxi Medical University in August 2021 was selected as the study subject. The proband was subjected to whole exome sequencing, and candidate variant was verified by Sanger sequencing and bioinformatic analysis. RESULTS: The proband was found to have harbored a heterozygous c.110T>C variant in exon 3 of the KIF1A gene, which can cause substitution of isoleucine by threonine at position 37 (p.I37T) and alter the function of its protein product. The same variant was not found in his parents, elder brother and elder sister, suggesting that it has a de novo origin. Based on the guidelines of the American College of Medical Genetics and Genomics (ACMG), the variant was rated as likely pathogenic (PM2_Supporting+PP3+PS2). CONCLUSION The c.110T>C variant of the KIF1A gene probably underlay the HSP30 in the proband. Above finding has enable genetic counseling for this family.
Humans ; Male ; East Asian People ; Kinesins/genetics* ; Mutation ; Pedigree ; Spastic Paraplegia, Hereditary/genetics* ; Female

In the early stage of diabetes retinopathy(DR),the change in the molecular level is often earlier than chan-ges in retinal microvessels.Under the chronic high-glucose environment,oxidative stress,epigenetic changes and other mechanisms cause retinal mitochondrial DNA(mtDNA)damage,affect the transcription process of mtDNA coding genes,and damage the electronic transport chain,leading to a vicious cycle of free radicals,which accelerates the apoptosis of retinal capillary pericytes and endothelial cells,leads to retinal microcirculation dysfunction,and cause DR.This paper will review the epigenetic changes,oxidative stress,damage to replication and repair system,gene mutation and other aspects,in order to elaborate on the research progress of retinal mtDNA damage in the pathogenesis of DR.