1.Reconceptualizing Critical Illness in Cancer Through the Lens of Host Unregulated Response
Yun CHU ; Shiyi GONG ; Xin DING ; Hua ZHAO ; Huan CHEN ; Qing ZHANG ; Xiaoting WANG
Medical Journal of Peking Union Medical College Hospital 2026;17(1):1-9
Onco-critical care has emerged as an important subspecialty at the intersection of critical care medicine and oncology, attracting increasing attention in recent years. With continuous innovations in cancer therapies, patient survival has improved significantly; however, the incidence of associated critical complications has also increased. The reasons for cancer patients requiring intensive care unit admission are diverse and can be broadly categorized into three groups: progression of the underlying malignancy, treatment-related complications, and coexisting classical critical illnesses. Traditional critical care concepts and practices face limitations in addressing the multidimensional and heterogeneous challenges of onco-critical care. Based on the core mechanism of critical illness development—host/organ unregulated response (HOUR)—this article systematically elaborates on how this framework advances understanding and clinical practice into onco-critical care, with emphasis on its manifestations in neuroendocrine, immune-inflammatory, and coagulation-metabolic pathways. The review summarizes recent advances in clinical assessment and phenotyping systems for onco-critical illness and discusses a multidisciplinary, integrated management strategy centered on the "Disease Control, Host Response Modulation, Organ Support" triad. Finally, major challenges and future directions in this field are outlined. By integrating existing evidence and theoretical insights, this review aims to provide new perspectives and a theoretical foundation for the clinical management of onco-critical illness, thereby promoting its evolution toward precision and standardization.
2.Surveillance of Oncomelania hupensis snails following interruption of schistosomiasis transmission in Yunnan Province
Siqi NING ; Yi DONG ; Chunhong DU ; Lifang WANG ; Yun ZHANG ; Yuhe HE ; Hua JIANG ; Jiayu SUN ; Chunqiong CHEN ; Jiaqi YAN ; Jihua ZHOU ; Zongya ZHANG ; Hongqiong WANG ; Meifen SHEN ; Jing SONG
Chinese Journal of Schistosomiasis Control 2026;38(2):200-206
Objective To investigate the distribution characteristics of Oncomelania hupensis snails in Yunnan Province fol-lowing interruption of schistosomiasis transmission, so as to provide the evidence for assessing the risk of schistosomiasis transmission and scientifically formulating the schistosomiasis surveillance program. Methods According to the requirements of the National Schistosomiasis Surveillance Scheme (2020 Edition), O. hupensis snail surveillance data were collected from 18 schistosomiasis-endemic counties (cities, districts) in Yunnan Province from 2020 to 2024, including area of snail survey, area of snail habitats, area of re-emerging snail habitats, number of frames surveyed, number of frames with O. hupensis snails, number of O. hupensis snails captured, and number of living snails, and the occurrence of frames with snails and mean density of living snails were calculated. Changes in snail status over the 5-year period from 2020 to 2024 and the differences in snail distributions specified by epidemic intensity, environmental type, and vegetation type were analyzed. Results The areas of snail survey increased from 1 727.96 hm2 in 2020 to 3 894.45 hm2 in 2024 (peak) across 18 schistosomiasis-endemic counties (cities, districts) in Yunnan Province during the period from 2020 through 2024. The areas of snail habitats increased from 70.36 hm2 in 2020 to a peak in 2023 (172.04 hm2), followed by a reduction to 132.36 hm2 in 2024, and the areas of re-emerging snail habitats increased from 42.71 hm2 in 2020 to a peak in 2022 (78.43 hm2), followed by a reduction to 40.21 hm2 in 2024. The occurrence of frames with snails and mean density of living snails increased from 1.24% (3 025/244 404) and (0.033 2 ± 0.038 7) snails/0.1 m2 in 2020 to peaks at 2.03% (6 231/307 563) and (0.066 9 ± 0.068 4) snails/0.1 m2 in 2023, followed by reductions to 1.04% (5 829/559 941) and (0.032 6 ± 0.057 7) snails/0.1 m2 in 2024, respectively. There was a significant difference in the occurrence of frames with snails over the 5-year study period (χ2 = 1 962.95, P < 0.05), and the occurrence of frames with snails reduced by 48.71% in 2024 relative to in 2023 (χ2 = 1 411.05, P < 0.005); however, there was no significant difference in the mean density of living snails over the 5 years (H = 5.310, P > 0.05). There were significant differences in the occurrence of frames with snails (χ2 = 481.27, P < 0.05) and mean density of living snails (H = 6.872, P < 0.05) in schistosomiasis-endemic areas with different epidemic intensities. The occurrence of frames with snails (χ2 = 25.32 and 38.70, both P values < 0.017) and mean density of living snails (Z = 28.55 and 49.96, both P values < 0.017) were higher in schistosomiasis transmission-interrupted and eliminated areas with snails than in schistosomiasis-eliminated areas without snails, and the occurrence of frames with snails (χ2 = 453.54, P < 0.017) and mean density of living snails (Z = −56.97, P < 0.017) were higher in schistosomiasis-eliminated areas with snails than in schistosomiasis transmission-interrupted areas with snails. O. hupensis snails were mainly distributed in paddy fields, dry farmlands and ditches; however, the occurrence of frames with snails (13.40%, 424/3 164) and mean density of living snails [(0.252 8 ± 0.158 7) snails/0.1 m2] were higher in ponds/weirs than in other types of environments (both P values < 0.05). Rice, dry farmland crops and weeds were main vegetations in which O. hupensis snails were distributed, and the occurrence of frames with snails (2.29%, 7 111/310 140) and mean density of living snails [(0.072 3 ± 0.018 9) snails/0.1 m2] were higher in weeds than in other types of environments (both P values < 0.05). Conclusions O. hupensis snails have been effectively controlled in Yunnan Province following implementation of integrated schistosomiasis control measures; however, there are still risk factors for schistosomiasis transmission, including reduced attention to schistosomiasis control and snail re-emergence. Improved control efforts and surveillance system construction and timely identification of risk factors of snail status and timely management are recommended to ensure the achievement of the target of schistosomiasis elimination as scheduled.
3.Surveillance of Schistosoma japonicum infections in wild murines in Yunnan Province
Meifen SHEN ; Jing SONG ; Lifang WANG ; Yun ZHANG ; Hua JIANG ; Jihua ZHOU ; Jiaqi YAN ; Jiayu SUN ; Chunqiong CHEN ; Zongya ZHANG ; Hongqiong WANG ; Chunhong DU ; Yi DONG
Chinese Journal of Schistosomiasis Control 2026;38(3):299-303
Objective To investigate the prevalence of Schistosoma japonicum infections in wild murines in schistosomiasisendemic areas of Yunnan Province, so as to provide the evidence for improving the schistosomiasis surveillance and early warning capability and implementing precise interventions in the province. Methods A total of 56 natural villages were sampled from 14 schistosomiasis-endemic counties (cities, districts) in Yunnan Province as surveillance sites from 2024 to 2025. Wild murines were captured using traps at night and characterized for species. Liver samples were collected from wild murines, S. japonicum eggs and miracidia were simultaneously detected using liver tissue compression microscopy, liver tissue homogenate microscopy, and liver tissue homogenate hatching. In addition, stool samples were collected from wild murine rectum, with S. japonicum eggs detected using a modified Kato-Katz thick smear technique and S. japonicum miracidia detected using the hatching test with nylon gauzes. Results A total of 15 577 valid murine traps were recovered, and 891 wild murines belonging to 16 species were captured, with a capture rate of 5.72%(891/15 577). The captured wild murines were predominantly districted in paddy fields, dry lands, ditches, ponds and marshlands, with Apodemus chevrieri, Rattus norvegicus, Crocidura attenuata, R. rattus sladeni, R. flavipectus, and Eothenomys miletus as dominant species. No S. japonicum eggs or miradicia were in laboratory; however, other parasites were identified in 25 wild murines. The prevalence rates of Schistosoma sinensis, Capillaria hepatica and Hymenolepis nana were 2.24% (20/891), 0.90% (8/891) and 0.56% (5/891), and the prevalence of S. sinensis and C. hepatica co-infection was 0.90% (8/891), respectively. Conclusions S. sinensis, C. hepatica and H. nana are predominant parasite species in wild murines in schistosomiasis-endemic areas of Yunan Province. No S. japonicum infection was detected during the study period; however, there is still a risk of wild murines as a potential source of infection for schistosomiasis transmission. Continuous intensified surveillance of S. japonicum infections in wild murines is a critical programme in schistosomiasis surveillance and early warning in Yunnan Province.
4.Effect of Zhengan Xifengtang on Intestinal Mucosal Barrier in Spontaneously Hypertensive Rats via FXR-MLCK/p-MLC Pathway
Meilong SI ; Hua JIN ; Yu WANG ; Qiuju ZHANG ; Tao LIU ; Yun YONG ; Xuan BAO
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(21):1-10
ObjectiveTo investigate the repair effects of Zhengan Xifengtang on intestinal mucosal barrier in spontaneously hypertensive rats (SHRs) through the pathways of farnesoid X receptor (FXR)-myosin light chain kinase (MLCK)/phosphorylated myosin light chain (p-MLC) and its potential mechanism. MethodsForty 10-week-old male SHRs were randomly divided into model group, amlodipine besylate group (0.5 mg·kg-1·d-1), and high, middle and low dose groups of Zhengan Xifengtang (34.5, 17.25, 8.625 g·kg-1·d-1); eight age-matched male Wistar-Kyoto (WKY) rats of the same origin served as the normal control group. Drug intervention was carried out for 8 weeks, and the blood pressure of the rats was measured regularly. After the intervention, the rats were euthanized to collect tissue samples. Hematoxylin and eosin (HE) staining and Alcian blue-periodic acid-Schiff (AB-PAS) staining were used to evaluate the pathological morphology and the number of goblet cells in colonic mucosa. Enzyme-linked immunosorbent assay (ELISA) was employed to measure plasma lipopolysaccharide (LPS) and diamine oxidase (DAO) levels in each group of rats. Immunofluorescence (IF) assay was used to detect the relative fluorescence intensity of FXR and p-MLC in colonic tissue. Western blot was used to detect the zonula occludens-1 (ZO-1), Occludin, Claudin-1, junctional adhesion molecule-1 (JAM-1), mucin-2 (MUC2), FXR, MLCK, and p-MLC protein expression in colon tissue. Real-time fluorescence quantitative polymerase chain reaction (Real-time PCR) was used to detect mRNA expression levels of ZO-1, Occludin, Claudin-1, JAM-1, MUC2, FXR, MLCK, and MLC in colon tissue. ResultsCompared with the normal group, the blood pressure in the model group increased significantly (P<0.01), the colonic mucosal structure was seriously damaged, and the number of goblet cells decreased significantly. The contents of LPS and DAO increased significantly (P<0.01), the relative fluorescence intensity of FXR in colon decreased, while that of p-MLC increased (P<0.01). The protein and mRNA expressions of ZO-1, Claudin-1, JAM-1, Occludin, MUC2 and FXR decreased significantly (P<0.01), whereas the protein expression of MLCK and p-MLC increased significantly (P<0.01). Additionally, the mRNA expression of MLCK and MLC increased significantly (P<0.01). Compared with the model group, the Zhengan Xifengtang groups at various dosages and the amlodipine besylate group showed significantly reduced blood pressure (P<0.01). The damage of colonic mucosa structure was alleviated, the infiltration of inflammatory cells decreased, and the number of goblet cells increased. LPS and DAO levels were decreased (P<0.05, P<0.01). In the colon, the relative fluorescence intensity of FXR increased, while that of p-MLC decreased (P<0.05, P<0.01). The protein and mRNA expression levels of ZO-1, Claudin-1, JAM-1, Occludin, and FXR increased significantly (P<0.05, P<0.01), while the protein expression of MLCK and p-MLC decreased significantly (P<0.05, P<0.01). Furthermore, the mRNA expression of MLCK and MLC decreased significantly (P<0.05, P<0.01), and the protein expression of MUC2 increased significantly (P<0.05, P<0.01). The expression of MUC2 mRNA in each dose group of Zhengan Xifengtang increased significantly (P<0.05, P<0.01). ConclusionZhengan Xifengtang may regulate the FXR-MLCK/p-MLC signaling pathway and enhance the expression of tight junction protein, thereby reducing intestinal mucosal permeability, promoting mucosal barrier repair, decreasing LPS release into the blood, and ultimately lowering blood pressure.
5.Effect of Zhengan Xifengtang on Intestinal Mucosal Barrier in Spontaneously Hypertensive Rats via FXR-MLCK/p-MLC Pathway
Meilong SI ; Hua JIN ; Yu WANG ; Qiuju ZHANG ; Tao LIU ; Yun YONG ; Xuan BAO
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(21):1-10
ObjectiveTo investigate the repair effects of Zhengan Xifengtang on intestinal mucosal barrier in spontaneously hypertensive rats (SHRs) through the pathways of farnesoid X receptor (FXR)-myosin light chain kinase (MLCK)/phosphorylated myosin light chain (p-MLC) and its potential mechanism. MethodsForty 10-week-old male SHRs were randomly divided into model group, amlodipine besylate group (0.5 mg·kg-1·d-1), and high, middle and low dose groups of Zhengan Xifengtang (34.5, 17.25, 8.625 g·kg-1·d-1); eight age-matched male Wistar-Kyoto (WKY) rats of the same origin served as the normal control group. Drug intervention was carried out for 8 weeks, and the blood pressure of the rats was measured regularly. After the intervention, the rats were euthanized to collect tissue samples. Hematoxylin and eosin (HE) staining and Alcian blue-periodic acid-Schiff (AB-PAS) staining were used to evaluate the pathological morphology and the number of goblet cells in colonic mucosa. Enzyme-linked immunosorbent assay (ELISA) was employed to measure plasma lipopolysaccharide (LPS) and diamine oxidase (DAO) levels in each group of rats. Immunofluorescence (IF) assay was used to detect the relative fluorescence intensity of FXR and p-MLC in colonic tissue. Western blot was used to detect the zonula occludens-1 (ZO-1), Occludin, Claudin-1, junctional adhesion molecule-1 (JAM-1), mucin-2 (MUC2), FXR, MLCK, and p-MLC protein expression in colon tissue. Real-time fluorescence quantitative polymerase chain reaction (Real-time PCR) was used to detect mRNA expression levels of ZO-1, Occludin, Claudin-1, JAM-1, MUC2, FXR, MLCK, and MLC in colon tissue. ResultsCompared with the normal group, the blood pressure in the model group increased significantly (P<0.01), the colonic mucosal structure was seriously damaged, and the number of goblet cells decreased significantly. The contents of LPS and DAO increased significantly (P<0.01), the relative fluorescence intensity of FXR in colon decreased, while that of p-MLC increased (P<0.01). The protein and mRNA expressions of ZO-1, Claudin-1, JAM-1, Occludin, MUC2 and FXR decreased significantly (P<0.01), whereas the protein expression of MLCK and p-MLC increased significantly (P<0.01). Additionally, the mRNA expression of MLCK and MLC increased significantly (P<0.01). Compared with the model group, the Zhengan Xifengtang groups at various dosages and the amlodipine besylate group showed significantly reduced blood pressure (P<0.01). The damage of colonic mucosa structure was alleviated, the infiltration of inflammatory cells decreased, and the number of goblet cells increased. LPS and DAO levels were decreased (P<0.05, P<0.01). In the colon, the relative fluorescence intensity of FXR increased, while that of p-MLC decreased (P<0.05, P<0.01). The protein and mRNA expression levels of ZO-1, Claudin-1, JAM-1, Occludin, and FXR increased significantly (P<0.05, P<0.01), while the protein expression of MLCK and p-MLC decreased significantly (P<0.05, P<0.01). Furthermore, the mRNA expression of MLCK and MLC decreased significantly (P<0.05, P<0.01), and the protein expression of MUC2 increased significantly (P<0.05, P<0.01). The expression of MUC2 mRNA in each dose group of Zhengan Xifengtang increased significantly (P<0.05, P<0.01). ConclusionZhengan Xifengtang may regulate the FXR-MLCK/p-MLC signaling pathway and enhance the expression of tight junction protein, thereby reducing intestinal mucosal permeability, promoting mucosal barrier repair, decreasing LPS release into the blood, and ultimately lowering blood pressure.
6.Quality evaluation of Gegen Formula Granules
Dai-liang ZHANG ; Chun-xia WANG ; Lei SHI ; Yu-kang LIU ; Yong-qiang LIN ; Yu-zhuo WANG ; Jing-hua ZHANG ; Jin-xin LI ; Gui-yun CAO ; Zhao-qing MENG
Chinese Traditional Patent Medicine 2025;47(5):1421-1431
AIM To evaluate the quality of Gegen Formula Granules.METHODS Linear calibration with two reference substances(LCTRS)was adopted in the predicting of retention time with puerarin and daidzein as internal standards.UPLC characteristic chromatograms were established.The contents of 3'-hydroxy puerarin,puerarin(internal standard),3'-methoxy puerarin,puerarin 6"-O-xyloside,puerarin apioside and daidzin were determined by quantitative determination analysis multi-components by a single marker(QAMS),after which their transfer rates were calculated.RESULTS Compared with relative retention time method,LCTRS demonstrated higher positional accuracy for characteristic peaks and wider application range for columns.There were 9 characteristic peaks in the characteristic chromatograms for 14 batches of formula granules and 15 batches of standard decoctions with the similarities of more than 0.95.The contents and transfer rates of various constituents in formula granules and standard decoctions were basically consistent.CONCLUSION The chemical constituents in formula granules and their standard decoctions of Puerariae lobatae Radix display good consistency,reliable preparation process is observable in the former.
7.Guideline for diagnosis and treatment of infection after internal fixation of closed lower limb fractures in adults (version 2025)
Bobin MI ; Faqi CAO ; Weixian HU ; Wu ZHOU ; Chenchen YAN ; Hui LI ; Yun SUN ; Yuan XIONG ; Jinmi ZHAO ; Qikai HUA ; Xinbao WU ; Xieyuan JIANG ; Dianying ZHANG ; Zhongguo FU ; Dankai WU ; Guangyao LIU ; Guodong LIU ; Tengbo YU ; Jinhai TAN ; Xi CHEN ; Fengfei LIN ; Zhangyuan LIN ; Dongfa LIAO ; Aiguo WANG ; Shiwu DONG ; Gaoxing LUO ; Zhao XIE ; Dong SUN ; Dehao FU ; Yunfeng CHEN ; Changqing ZHANG ; Kun LIU ; Deye SONG ; Yongjun RUI ; Fei WU ; Ximing LIU ; Junwen WANG ; Meng ZHAO ; Biao CHE ; Bing HU ; Chengjian HE ; Guanglin WANG ; Xiao CHEN ; Guandong DAI ; Shiyuan FANG ; Wenchao SONG ; Ming CHEN ; Guanghua GUO ; Yongqing XU ; Lei YANG ; Wenqian ZHANG ; Kun ZHANG ; Xin TANG ; Hua CHEN ; Weiguo XU ; Shuquan GUO ; Yong LIU ; Xiaodong GUO ; Zhewei YE ; Liming XIONG ; Tian XIA ; Hongbin WU ; Qisheng ZHOU ; Mengfei LIU ; Yiqiang HU ; Yanjiu HAN ; Hang XUE ; Kangkang ZHA ; Wei CHEN ; Zhiyong HOU ; Bin YU ; Jiacan SU ; Peifu TANG ; Baoguo JIANG ; Guohui LIU
Chinese Journal of Trauma 2025;41(5):421-432
Postoperative infection of internal fixation of closed fractures the lower limbs in adults represents a devastating complication, characterized by diagnostic challenges, prolonged treatment duration and high disability rates. Current management of these infections faces multiple challenges, such as difficulties in early accurate diagnosis, and various controversies about the treatment plan, leading to poor overall diagnosis and treatment results. To address these issues, based on evidence-based medicine and principles with emphasis on scientific rigor, clinical applicability and innovation, the Trauma Branch of the Chinese Medical Association, Orthopedic Branch of the Chinese Medical Doctor Association, Orthopedics Branch of the Chinese Medical Association, and Trauma Orthopedics and Polytrauma Group of the Resuscitation and Emergency Committee of the Chinese Medical Doctor Association have collaboratively organized a panel of relevant experts to develop the Guideline for diagnosis and treatment of infection after internal fixation of closed lower limb fractures in adults ( version 2025). The guideline proposed 10 recommendations, aiming to provide a foundation for standardized diagnosis and treatment of postoperative infection in adults with closed lower limb fractures.
8.Guideline for the prevention of intraoperative acquired pressure injury in paraplegic patients with spinal cord injury (version 2025)
Aijun XU ; Shuixia LI ; Bo CHEN ; Mengyuan YE ; Lejiao LANG ; Ning NING ; Lin ZHANG ; Changqing LIU ; Zhonglan CHEN ; Weihu MA ; Weishi LI ; Xiaoning WANG ; Dongmei BIAN ; Jiancheng ZENG ; Xin WANG ; Yuan GAO ; Yaping CHEN ; Jiali CHEN ; Yun HAN ; Xiuting LI ; Yang ZHOU ; Xiaojing SU ; Qiong ZHANG ; Tianwen HUANG ; Ping ZHANG ; Hua LIN ; Xingling XIAO ; Ruifeng XU ; Fanghui DONG ; Bing HAN ; Luo FAN ; Yanling PEI ; Suyun LI ; Xiaoju TAN ; Rongchen GUO ; Yefang ZOU ; Xiaoyun HAN ; Junqin DING ; Yi WANG ; Shuhua DENG ; Jinli GUO ; Yinhua LIANG ; Yuan CEN ; Xiaoqin LIU ; Junru CHEN ; Haiyang YU ; Lunlan LI ; Ying REN ; Yunxia LI ; Jianli LU ; Ying YING ; Lan WEI ; Yin WANG ; Qinhong XU ; Yanqin ZHANG ; Yang LYU ; Shijun ZHANG ; Sui WENJIE ; Sanlian HU ; Shuhong YANG ; Guoqing LI ; Jingjing AN ; Baorong HE ; Leling FENG
Chinese Journal of Trauma 2025;41(6):530-541
Paraplegia caused by spinal cord injury is a serious neurological complication, for which surgery is currently the main treatment method. Due to different surgical approaches, patients are usually expected to maintain a passive prone position for a long time or switch between the supine and prone positions. Affected by multiple factors such as neurogenic sensory disorders, pathological changes in muscle tone and operative duration, the risk of intraoperative acquired pressure injury (IAPI) is significantly increased. Current clinical prevention strategies for IAPI in these patients predominantly focus on localized pressure relief during positioning, lacking systematic, standardized comprehensive prevention protocols or evidence-based guidelines. To address it, Department of Nursing, Orthopedics Branch, China International Exchange and Promotive Association for Medical and Health Care, Spinal Trauma Professional Committee, Orthopedics Branch, Chinese Medical Doctor Association, Nursing Group of Spine and Spinal Cord Professional Committee of Chinese Association of Rehabilitation Medicine organized experts in relevant fields to formulate Guideline for the prevention of intraoperative acquired pressure injury in paraplegic patients with spinal cord injury ( version 2025), based on evidence-based medical evidence and latest research results and clinical practice at home and abroad. Eleven recommendations were put forward from the aspects of preoperative risk assessment, intraoperative prevention strategies, postoperative handover and monitoring, and supportive mechanisms for IAPI prevention, aiming to standardize the prevention measures and management strategies of IAPI in paraplegic patients with spinal cord injury and accelerate the recovery of patients and improve the therapeutic effect.
9.A multicenter retrospective study on clinicopathological features, gene variation profiles and prognostic analysis of previously untreated diffuse large B - cell lymphoma
Yongning JIANG ; Jie ZHANG ; Yaping ZHANG ; Yi XIA ; Yi MIAO ; Haiwen NI ; Jinning SHI ; Xiaohui ZHANG ; Min XU ; Haiying HUA ; Yun ZHUANG ; Wenzhong WU ; Maozhong XU ; Xiaoyan XIE ; Zhuxia JIA ; Yuqing MIAO ; Min ZHAO ; Jianyong LI ; Wenyu SHI
Chinese Journal of Medical Genetics 2025;42(9):1069-1077
Objective:To explore the impact of age on the genetic variant spectrum and prognosis of patients with previously untreated Diffuse large B-cell lymphoma (DLBCL).Methods:A retrospective analysis was conducted on the clinical data and follow-up information of 254 previously untreated DLBCL patients from 14 hospitals in the Jiangsu Cooperative Lymphoma Group (JCLG) enrolled from July 2018 and July 2023. Following extraction of DNA from tumor tissue samples, next-generation sequencing (NGS) technique was employed to analyze the genetic variant spectrum of the DLBCL patients, with an evaluation of the relationship between age and genetic variants as well as prognosis. This study was approved by the Medical Ethics Committee of the Affiliated Hospital of Nantong University (Ethics No.: 2023-K048-01).Results:The median age of the 254 DLBCL patients was 62 years old, with 55% of patients aged 60 years or above. Clinical evaluation showed that younger (< 60 years) patients had higher complete response (CR) (70% vs. 59%), and objective response rate (ORR) (88% vs. 79%) than older patients, though the difference between the two groups was not statistically. Survival analysis indicated that both the five-year overall survival (OS) (82.7% vs. 71.7%, P=0.006) and progression-free survival (PFS) (70.6% vs. 50.2%, P<0.05) rates were significantly higher in younger patients. NGS showed that 99.6% of the patients harbored genetic variants, with PIM1, KMT2D, TP53, MYD88, and CD79B being the most common genes. Age significantly affected the variant frequency of certain genes, with MYC variants serving an adverse prognostic factor for OS in younger patients ( P=0.001), while TP53 ( P=0.024) and BCL2 ( P=0.002) variants significantly impacted OS in older patients. Prognostic analysis identified age ≥ 60 years ( HR=3.439, 95% CI=1.318~9.874), presence of B symptoms ( HR = 2.871, 95% CI=1.133~7.307), and elevated lactate dehydrogenase ( HR=3.528, 95% CI=1.231~10.66) as independent adverse prognostic factors. Conclusion:Age, genetic variants, and clinical factors may significantly affect the prognosis of the DLBCL patients. Younger patients have better survival compared to older patients. Variants of the MYC, BCL2, and TP53 genes are closely associated with poor prognosis.
10.A case report of premature ovarian insufficiency caused by a novel FANCL mutation(c.1033G>A)and in vitro functional validation
Yi-qing LIU ; Shu-ting REN ; Yun-cheng PAN ; Feng ZHANG ; Xiao-jin ZHANG ; Yan-hua WU
Fudan University Journal of Medical Sciences 2025;52(2):270-276,291
Objective To investigate the characteristics of a novel FANCL mutation identified in a patient with premature ovarian insufficiency(POI)and to explore its potential functional impacts in vitro.Methods A novel FANCL heterozygous mutation c.1033G>A(p.Glu345Lys)was screened in a patient with POI using whole exome sequencing(WES),which was found to be inherited from a mother who had undergone early menopause.The authenticity of the mutation was identified by Sanger sequencing and the conserved nature of the mutation site was predicted by software.Overexpressing FANCL mutant and wildtype plasmids were constructed and transiently transfected into HEK293T cell lines,and the effect of the mutation was detected by qPCR,immunofluorescence and Western blot.Results The mutation site of FANCL was located within the Ring domain of FANCL,which was highly conserved across multiple species.The mutant showed no significant change in mRNA expression level,while the protein expression level was significantly down-regulated.In vitro cellular experiments further revealed that the mutation leads to decreased expression levels by reducing protein stability.Conclusion A FANCL c.1033G>A mutation was found and it may cause disease in the POI patient due to decreased protein stability.

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