1.Current quality status and management countermeasures of occupational health technical services in Zhejiang Province
Qiuliang XU ; Feng HAN ; Peng WANG ; Zhen ZHOU ; Fei LI ; Hongwei XIE ; Yong HU ; Weiming YUAN ; Lifang ZHOU ; Hua ZOU
Journal of Environmental and Occupational Medicine 2026;43(3):341-346
Background The quality of occupational health technical services is directly linked to the protection of workers' health rights and the efficacy of occupational disease prevention and control. However, the industry still faces critical challenges: sporadic instances of institutional non-compliance and persistent irregularities in professional practice continue to undermine overall service performance. Objective To assess the current quality status of occupational health technical services in Zhejiang Province and propose countermeasures for quality improvement, providing a scientific basis for policy optimization and service delivery quality enhancement. Methods A total of 69 occupational health technical service institutions in Zhejiang Province that obtained formal accreditation as of April 30, 2024, were sampled, including 3 public institutions and 66 private institutions (comprising 3 formerly Class-A, 28 formerly Class-B, 11 formerly Class-C, and 24 newly certified institutions). Following the Technical Protocol for Quality Monitoring of Occupational Health Technical Service in Zhejiang Province and the Technical Protocol for Proficiency Testing of Occupational Health Detection in Zhejiang Province, a quality assessment task force comprising national and provincial experts was established. Evaluation was conducted across four dimensions: qualification maintenance and compliance, standardization of technical services, authenticity of technical services, and proficiency testing, utilizing a combination of document review, on-site inspections, and technical skill assessments. Results The occupational health technical service institutions in Zhejiang Province were predominantly private entities (82.5%), with significant disparities in overall service quality. The pass rates for qualification maintenance and compliance, technical service standardization, technical service authenticity, and the excellence rate for laboratory proficiency testing were 81.5%, 80.7%, 97.3%, and 90.4%, respectively. Regarding qualification maintenance, the pass rates for "environmental conditions" (49.8%, 56.7%) and "instrumentation and equipment" (58.2%、65.6%) were significantly lower for formerly Class-C and newly certified institutions compared to other categories. In terms of technical standardization, "standardized on-site inspections" recorded the lowest pass rate (67.4%), with newly certified institutions at only 48.0%. Regarding technical service authenticity, formerly Class-C institutions exhibited issues such as missing raw chromatograms for blank samples (85.7% pass rate). In laboratory proficiency testing, public and formerly Class-A institutions achieved 100% excellence rates, but the performance of formerly Class-C and newly certified institutions was comparatively weak; specifically, the failure rate for organic analysis in formerly Class-C institutions reached 20%; the failure rate for dust testing items in newly certified institutions was 10.3%. Conclusion The overall quality of occupational health technical services in Zhejiang Province still requires significant improvement, particularly in basic institutional conditions, the standardization of on-site inspections, and laboratory proficiency in organic and dust analysis. Formerly Class-C and newly certified institutions should be the primary focus of quality management efforts. Differentiated regulatory strategies are recommended, alongside strengthening interim and ex-post supervision to gradually enhance the quality of occupational health technical services across all institutions.
2.The Diversity of Filamentous Morphologies and Magnetic Sensitivity Modulated by Diverse MagR Expression in Bacteria
Ya-Fei CHANG ; Jing ZHANG ; Peng ZHANG ; Xiu-Juan ZHOU ; Meng-Ke WEI ; Tian-Tian CAI ; Pei-Qi HE ; Jun-Feng WANG ; Can XIE
Progress in Biochemistry and Biophysics 2026;53(5):1439-1456
Objective Magnetoreception, the remarkable ability of diverse animals to sense and utilize the geomagnetic field for orientation and navigation, remains a molecularly unresolved mystery in sensory biology. The putative magnetoreceptor (MagR, previously known as IscA1) is a highly conserved iron-sulfur protein implicated in both magnetoreception and iron metabolism; however, the functional diversity among its cross-species homologs remains poorly understood. Cellular morphology is a key genetically determined trait that can be altered through genetic or environmental modifications—a process known as cell morphology engineering. Constructing engineered cells with specific morphological features and magnetic sensitivity to achieve remote, non-invasive magnetic modulation represents a crucial goal in this field with significant application potential. Therefore, this study aims to systematically investigate the effects of MagR heterologous expression on bacterial morphology and magnetic sensing capabilities, screen for MagR-based magnetically sensitive morphology engineering pathways, and reveal the underlying molecular mechanisms. Methods We systematically screened 28 MagR homologous genes from diverse prokaryotic and animal taxa to evaluate their expression and corresponding phenotypic effects in Escherichia coli (E. coli). To compare the differential magnetic responses among bacteria expressing various recombinant MagR proteins, we utilized high-throughput automated bright-field microscopic imaging and scanning electron microscopy (SEM). Furthermore, comprehensive biochemical and biophysical characterizations of iron and iron-sulfur cluster binding were performed using Ferrozine colorimetric assays, electron paramagnetic resonance (EPR) spectroscopy, ultraviolet-visible (UV-Vis) absorption, and circular dichroism (CD) spectroscopy. Additionally, 100 mT static magnetic field (SMF) exposure experiments were conducted to assess magnetically tunable phenotypes, while the intrinsic magnetic properties of purified MagR proteins were directly measured using a superconducting quantum interference device (SQUID) magnetometer. Results Our results demonstrated that the heterologous expression of MagR homologs induced varying degrees of bacterial filamentation. From this comprehensive screen, two distinct morphological patterns were identified: hydra (Hydra vulgaris) MagR (hyMagR) promoted uniform cell elongation and filamentation, exhibiting robust magnetic sensitivity manifested as significantly enhanced filamentation under the 100 mT SMF. In contrast, pigeon (Columba livia) MagR (clMagR) induced only low-frequency, extreme filamentation (sporadically exceeding 80 μm) with a relatively weaker magnetic morphological response. Mechanistically, our data unambiguously proved that these phenotypic differences are primarily driven by distinct iron redox preferences rather than total cellular iron accumulation. Specifically, hyMagR preferentially binds ferrous iron (Fe2+), whereas clMagR favors ferric iron (Fe3+) and forms more stable iron-sulfur clusters. Intriguingly, although SQUID magnetometry showed that purified clMagR exhibited approximately five-fold higher mass magnetic susceptibility than hyMagR, its cellular magnetic response was weaker. We hypothesize that the Fe2+-preferred intracellular environment associated with hyMagR overexpression primes the cell for enhanced generation of reactive oxygen species (ROS) via the Fenton reaction. Exposure to an SMF synergizes with this primed redox state, triggering the bacterial SOS response and upregulating cell division inhibitors to efficiently induce uniform filamentation. Conclusion Our findings identify the Fe2+/Fe3+ redox state as a critical determinant of MagR-mediated morphological remodeling and magnetic responsiveness. This discovery suggests a potential strategy for engineering magnetically responsive cellular systems for synthetic biology applications, and provides a plausible framework, which potentially combines intrinsic protein magnetism with redox-state modulation, for further investigating the evolutionary mechanisms of MagR-mediated magnetoreception.
3.The Diversity of Filamentous Morphologies and Magnetic Sensitivity Modulated by Diverse MagR Expression in Bacteria
Ya-Fei CHANG ; Jing ZHANG ; Peng ZHANG ; Xiu-Juan ZHOU ; Meng-Ke WEI ; Tian-Tian CAI ; Pei-Qi HE ; Jun-Feng WANG ; Can XIE
Progress in Biochemistry and Biophysics 2026;53(5):1439-1456
Objective Magnetoreception, the remarkable ability of diverse animals to sense and utilize the geomagnetic field for orientation and navigation, remains a molecularly unresolved mystery in sensory biology. The putative magnetoreceptor (MagR, previously known as IscA1) is a highly conserved iron-sulfur protein implicated in both magnetoreception and iron metabolism; however, the functional diversity among its cross-species homologs remains poorly understood. Cellular morphology is a key genetically determined trait that can be altered through genetic or environmental modifications—a process known as cell morphology engineering. Constructing engineered cells with specific morphological features and magnetic sensitivity to achieve remote, non-invasive magnetic modulation represents a crucial goal in this field with significant application potential. Therefore, this study aims to systematically investigate the effects of MagR heterologous expression on bacterial morphology and magnetic sensing capabilities, screen for MagR-based magnetically sensitive morphology engineering pathways, and reveal the underlying molecular mechanisms. Methods We systematically screened 28 MagR homologous genes from diverse prokaryotic and animal taxa to evaluate their expression and corresponding phenotypic effects in Escherichia coli (E. coli). To compare the differential magnetic responses among bacteria expressing various recombinant MagR proteins, we utilized high-throughput automated bright-field microscopic imaging and scanning electron microscopy (SEM). Furthermore, comprehensive biochemical and biophysical characterizations of iron and iron-sulfur cluster binding were performed using Ferrozine colorimetric assays, electron paramagnetic resonance (EPR) spectroscopy, ultraviolet-visible (UV-Vis) absorption, and circular dichroism (CD) spectroscopy. Additionally, 100 mT static magnetic field (SMF) exposure experiments were conducted to assess magnetically tunable phenotypes, while the intrinsic magnetic properties of purified MagR proteins were directly measured using a superconducting quantum interference device (SQUID) magnetometer. Results Our results demonstrated that the heterologous expression of MagR homologs induced varying degrees of bacterial filamentation. From this comprehensive screen, two distinct morphological patterns were identified: hydra (Hydra vulgaris) MagR (hyMagR) promoted uniform cell elongation and filamentation, exhibiting robust magnetic sensitivity manifested as significantly enhanced filamentation under the 100 mT SMF. In contrast, pigeon (Columba livia) MagR (clMagR) induced only low-frequency, extreme filamentation (sporadically exceeding 80 μm) with a relatively weaker magnetic morphological response. Mechanistically, our data unambiguously proved that these phenotypic differences are primarily driven by distinct iron redox preferences rather than total cellular iron accumulation. Specifically, hyMagR preferentially binds ferrous iron (Fe2+), whereas clMagR favors ferric iron (Fe3+) and forms more stable iron-sulfur clusters. Intriguingly, although SQUID magnetometry showed that purified clMagR exhibited approximately five-fold higher mass magnetic susceptibility than hyMagR, its cellular magnetic response was weaker. We hypothesize that the Fe2+-preferred intracellular environment associated with hyMagR overexpression primes the cell for enhanced generation of reactive oxygen species (ROS) via the Fenton reaction. Exposure to an SMF synergizes with this primed redox state, triggering the bacterial SOS response and upregulating cell division inhibitors to efficiently induce uniform filamentation. Conclusion Our findings identify the Fe2+/Fe3+ redox state as a critical determinant of MagR-mediated morphological remodeling and magnetic responsiveness. This discovery suggests a potential strategy for engineering magnetically responsive cellular systems for synthetic biology applications, and provides a plausible framework, which potentially combines intrinsic protein magnetism with redox-state modulation, for further investigating the evolutionary mechanisms of MagR-mediated magnetoreception.
4.Metabolic-dysfunction and alcohol-associated liver disease: A new concept and recent advances
Rutao LIN ; Fei XU ; Xin XIN ; Yiyang HU ; Qin FENG
Journal of Clinical Hepatology 2026;42(4):950-956
In 2023, multiple international societies proposed the concept of metabolic-dysfunction and alcohol-associated liver disease (MetALD) to characterize patients with steatotic liver disease who exhibit metabolic dysfunction and consume alcohol at a moderate level. In recent years, the evidence system in this field has been constantly developed and improved. This article reviews the latest research advances in MetALD from the aspects of background, definition, epidemiological characteristics, natural history, clinical phenotype, diagnostic and assessment methods, and treatment regimens, as well as the directions for future investigation.
5.Investigating Molecular Mechanisms of Qijia Rougan Prescription and Its Key Effect or Ingredients Against Hepatic Fibrosis Based on Macrophage M2 Polarization
Li WEN ; Quansheng FENG ; Cen JIANG ; Baixue LI ; Dong WANG ; Jike LI ; Xia LI ; Fei WAN ; Yanfeng ZHENG
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(14):155-165
ObjectiveBased on the regulation of macrophage M2 polarization, this study aims to explore the molecular mechanism and action targets of the Qijia Rougan prescription and its key effector ingredients in anti-fibrosis, thereby providing a basis and reference for the development of new drugs for hepatic fibrosis. MethodsA rat model of hepatic fibrosis was established by subcutaneous injection of 40%CCl4, followed by oral administration of Qijia Rougan granules. The volume of collagen fibers was detected using Masson staining, the fibrosis markers Collagen Ⅰ and α-SMA were detected using immunohistochemistry, the proportion of M2 macrophages was detected by flow cytometry. The expression levels of M2 macrophage phenotype markers CD163 and CD206 were detected using immunofluorescence double staining. Western blot was used to detect the levels of the transforming growth factor-β (TGF-β), platelet derived growth factor subunit B (PDGFB), interleukin-10 (IL-10), phosphorylated Janus kinase 1 (p-JAK1), and phosphorylated signal transducer and activator of transcription 6 (p-STAT6). Real-time fluorescent quantitative PCR was used to detect the relative expression levels of JAK1, STAT6, Arginase 1(Arg1), and Fizz1. Based on the theory of serum pharmacology, liquid chromatography-mass spectrometry and WENN analysis were used to obtain the active ingredients of Qijia Rougan prescription. Molecular docking and molecular dynamics simulation were performed to analyze the effector ingredients and their targets. The identified effector ingredients were interfered with IL-4-induced M2 polarization of RAW264.7 macrophage in vitro to validate the targets. ResultsQijia Rougan prescription significantly reduced the content of fibrosis markers α-SMA and Collagen Ⅰ, as well as collagen fiber content (P<0.05). It decreased the proportion of M2 macrophages and the levels of related cytokines IL-10, TGF-β and PDGFB, and up-regulated the levels of p-JAK1 and p-STAT6 (P<0.05). A total of 1 214 compounds were identified from Qijia Rougan prescription, medicated serum and blank serum, and 29 ingredients were finalized by Venn analysis, including 15 blood-entry prototypes and 14 drug metabolites. Molecular docking showed that enoxolone and berberine bound more strongly to JAK1, with binding free energies of -9.6 kcal·mol-1(1 cal≈4.184 J) and -9.1 kcal·mol-1, respectively. Molecular dynamics simulations showed that JAK1-enoxolone and JAK1-berberine exhibited stable simulation trajectories within 100 ns, with essentially identical conformations and high protein overlap before and after simulation. Their binding free energies were -25.18 5.0.81 kcal·mol-1 and -27.39 7.0.85 kcal·mol-1, respectively. The number of hydrogen bonds formed between JAK1 and enoxolone ranges from 0 to 5, and most of the time can be maintained at 2-3. In vitro intervention with enoxolone or berberine significantly reduced p-JAK1 and p-STAT6 levels (P<0.05). ConclusionQijia Rougan prescription inhibits M2 macrophage polarization in hepatic fibrosis. Enoxolone and berberine are the key effector ingredients of Qijia Rougan prescription to inhibit macrophage M2 polarization through targeting JAK1 and modulating the JAK1/STAT6 signaling pathway, thereby ameliorating hepatic fibrosis. This study provides a basis for prescription optimization, clinical application and new drug development, as well as a reference for monolithic anti-hepatic fibrosis research.
6.Characteristics of brain glymphatic system changes in patients with amnestic mild cognitive impairment based on perivascular spaces and DTI-ALPS index assessment
Xiaoqin CHENG ; Guoqiang FEI ; Shen ZHAO ; Rui HUA ; Feng SHI ; Xiaoli PAN ; Ziyi HE ; Sirui LIU
Chinese Journal of Clinical Medicine 2026;33(3):479-485
Objective To explore the characteristics and correlation between perivascular spaces (PVS) and diffusion tensor image analysis along perivascular spaces (DTI-ALPS) index in patients with amnestic mild cognitive impairment (aMCI). Methods A retrospective study was conducted on a total of 118 participants, including cognitive normal (CN) healthy controls and aMCI patients, recruited from the Department of Neurology, Zhongshan Hospital, Fudan University from September 2020 to September 2022. All participants underwent structural magnetic resonance imaging (MRI) and diffusion tensor imaging (DTI). An automatic segmentation algorithm was used to quantify PVS metrics in the brain, and DTI-ALPS index was calculated based on DTI. Differences in DTI-ALPS index and PVS metrics between the CN and aMCI groups were compared. Multivariate logistic regression was used to identify independent factors influencing aMCI. Correlation analysis was performed to assess relationships among DTI-ALPS index, PVS metrics, and cognitive scores. Results A total of 80 CN healthy controls and 38 aMCI patients were included. The DTI-ALPS index was significantly lower in the aMCI group compared with the CN group (1.28±0.18 vs 1.37±0.21, P=0.018), while differences in PVS metrics between groups were not statistically significant. Multivariate logistic regression analysis indicated that DTI-ALPS index was an independent factor affecting aMCI (OR=0.097, 95%CI 0.011–0.833, P=0.033). Correlation analysis revealed a positive relationship between DTI-ALPS index and MMSE score (r=0.210, P=0.023) as well as PVS length in the centrum semiovale (r=0.216, P=0.019). Conclusions The DTI-ALPS index may serve as an imaging biomarker for identifying early cognitive impairment, and patients with aMCI exhibit abnormal DTI-ALPS indices, suggesting that brain glymphatic system dysfunction may occur prior to morphological changes.
7.Minimally invasive management of spontaneous renal vascular rupture:a report of two cases
Jizong LYU ; Fei LIU ; Feng LI ; Guangli FAN ; Baoming YANG ; Siwei GONG ; Yuanlong ZHANG ; Yao ZHAI ; Ke WANG
Journal of Modern Urology 2026;31(2):157-159
Objective To investigate the diagnosis and treatment of 2 cases with spontaneous renal vascular rupture, and discuss the possible causes and treatment methods of this disease. Methods The clinical data and treatment methods of the 2 patients with spontaneous renal vascular rupture treated with renal artery embolization in Universal Global Xi'an Beihuan Hospital were analyzed. Relevant literature was reviewed to summarize the possible causes of this condition. Results The patients had no obvious history of trauma and no obvious abnormal coagulation function, and sought treatment due to sudden lumbar and abdominal pain. Laboratory tests revealed significantly decreased hemoglobin level, and elevated blood glucose (27.8, 27.6mmol/L). Abdominal computed tomography (CT) indicated perirenal hematoma and active bleeding. The bleeding arteries were located at the terminal branches of the anterior renal artery. Precise embolization was performed using CT angiography and selective renal artery angiography plus embolization, achieving an immediate hemostasis success rate of 100%. Postoperative hemoglobin level stabilized, and follow-up CT scans showed significant absorption of the perirenal hematoma without significant deterioration of renal function. Based on literature review and case analysis, the possible cause of spontaneous renal vascular rupture in these two patients was renal vascular sclerosis due to long-term diabetes. Other common etiologies of this condition included renal tumor, vascular malformation, and hypertension. Conclusion Spontaneous renal vascular rupture is rare. Renal artery embolization, as aminimally invasive treatment, can effectively control bleeding and protect renal function. The specific pathogenesis of this condition still requires further investigation. Long-term diabetes mellitus with poor blood glucose control may be associated factors, but more evidence is needed.
8.Observation on the effect of esketamine combined with general anesthesia and ultrasound-guided cervical plexus block in axillary endoscopic thyroidectomy
Rui LI ; Weifeng YAN ; Shengyang DENG ; Hua CHAI ; Fei FENG
China Journal of Endoscopy 2025;31(10):30-39
Objective To investigate the effect and safety of esketamine combined with general anesthesia and ultrasound-guided cervical plexus block in axillary endoscopic thyroidectomy.Methods The subjects of this study,112 female patients who underwent axillary endoscopic thyroidectomy in our hospital from January 2022 to October 2024,were randomly divided into an observation group and a control group,each with 56 cases.All patients were administered with ultrasound-guided cervical plexus block followed by general anesthesia.The observation group was injected with 0.1 mg/kg of esketamine prior to anesthesia induction and continuously pumped with esketamine at a rate of 0.1 mg/(kg·h)during the operation until sutures were completed,while the control group was administered with an equal volume of normal saline following the same procedure.The vital sign indicators[mean arterial pressure(MAP),heart rate(HR)and percutaneous arterial oxygen saturation(SpO2)]immediately after establishing electrocardiogram monitoring(T0),immediately before tracheal intubation(T1),immediately after tracheal intubation(T2),immediately after skin incision(T3)and immediately after the operation(T4)were compared between the two groups.Surgical related indicators such as propofol dosage,remifentanil dosage,and extubation time were also compared between them.Pain visual analogue scale(VAS)scores were performed on patients from the two groups at 1,6,12,and 24 h postoperatively.The 40-item quality of recovery score(QoR-40)was used before the surgeries and 1 d after surgeries to assess the patients.Adverse reactions were also compared.Results The difference was significant in terms of MAP,HR time effect in the two groups(F=24.63,F=20.11,P<0.05)and inter-group MAP,HR values(F=13.54,F=11.49,P<0.05).There were statistically significant differences in the interaction effects of MAP and HR between the two groups(F=4.10,F=3.46,P<0.05).The difference was not statistically significant in time,inter group,and interaction effects of SpO2(P>0.05).The dosage of propofol,remifentanil,and postoperative 1 d drainage in the observation group were less than those in the control group,the differences were statistically significant(P<0.05).The differences were not statistically signiciant in extubation time and awakening time between the two groups(P>0.05).The VAS scores at 1,6,12,and 24 h after operation in the observation groups were lower than those in the control group,the differences were statistically significant(P<0.05).Physical comfort,pain dimension ratings,and total score of the QoR-40 scale:1)those 1 d after operation were lower than those before operation in both groups(P<0.05);2)1 d after operation:those in the control group were lower than those in the observation group(P<0.05).The control group witnessed a remarkable decrease in QoR-40 emotional state rating 1 d after operation than it did before operation(P<0.05),while no significant change was seen by the observation group in this regard(P>0.05).The incidence of coughing after extubation in the observation group was lower than that in the control group(14.29%and 37.50%),the difference was statistically significant(P<0.05).The differences were not statistically signiciant in the incidence of other adverse reactions such as nausea,vomiting,dizziness,headache,respiratory depression,awakening restlessness and awakening delirium between the two groups(P>0.05).The total incidence of adverse reactions in the observation group was significantly lower than that in the control group(25.00%and 66.07%,P<0.05).Conclusion The application of esketamine combined with general anesthesia and ultrasound-guided cervical plexus block in axillary endoscopic thyroidectomy can significantly stabilize hemodynamics in patients,reduce postoperative pain,and promote postoperative recovery.It is worthy clinical application.
9.Clinical and imaging features of alveolar soft part sarcoma
Journal of Practical Radiology 2025;41(9):1529-1532
Objective To investigate the clinical and imaging features of alveolar soft part sarcoma(ASPS).Methods A retro-spective analysis was conducted on the clinical and imaging data of 41 patients with pathologically confirmed ASPS.Results The primary clinical manifestation of 41 patients with ASPS was progressive tumour enlargement.The tumors were located in the but-tocks(14 cases),thighs(11 cases),lower legs(5 cases),forearms(3 cases),upper arms(2 cases),psoas major muscles(2 cases),and one case each in the paracervical region,shoulder,axilla,and plantar regions.Pulmonary metastasis were observed in 30 patients,and 7 patients had metastases to other sites,including 2 cases of intracranial metastasis,1 case of lymph node metastasis,and 4 cases of bone and soft tissue metastasis.Five patients experienced postoperative local recurrence or metastasis.MR was performed in 34 patients,and CT was performed in 32 patients.The tumors were oval or irregular in shape.On CT,the tumors appeared as soft tissue density shadow,with calcification in 8 cases and 68%(17/25)showed marked enhancement with peripheral vascular plexus.On MR,the tumors exhibited isointense T1 and long T2 signals,67%(23/34)showed flow-void vessels within the tumor and 94%(32/34)showed tortuous vascular plexus at the tumor margins.Conclusion ASPS predominantly occurs in the muscles of buttocks and thigh and is prone to lung metastasis.Enhanced CT and MR can reveal vessels within and at the margins of the tumor,which is diagnosti-cally significant for ASPS.
10.Differences in prognosis between patients with metastatic urothelial carcinoma of different primary sites before and after the approval of ICIs:a cohort study based on the SEER database
Fei WANG ; Jiankang XU ; Yadong GE ; Qingfeng MENG ; Feng HE ; Jianpo ZHAI
Journal of Modern Urology 2025;30(10):833-841
Objective To compare the impact of different primary tumor sites on the survival of patients with metastatic urothelial carcinoma(mUC)before and after the approval of immune checkpoints inhibitors(ICIs)based on data from Surveillance,Epidemiology,and End Results(SEER).Methods The mUC cases during 2013 and 2017 in the SEER database were enrolled.Cohorts were defined by primary tumor sites(renal pelvis,ureter,bladder)and then stratified by ICIs availability into non-ICIs era(2013)and ICIs era(2017).The survival differences in each cohort between the two eras were compared,and stratified analysis was performed.The 2-year overall survival(OS)was assessed using Kaplan-Meier analysis and multivariable Cox proportional hazards analysis.Results A total of 1750 mUC cases were enrolled,with 785 cases in the non-ICIs era and 965 in the ICIs era.No significant differences existed across different anatomical sites in the non-ICIs era,whether in the whole urinary system or inside bladder.The 2-year survival rates were 23.5%for ureteral cancer,18.0%for renal pelvic cancer,and 15.9%for bladder cancer.Significant prognostic disparities emerged among patients based on primary tumor sites in ICIs era(P<0.05).The 2-year survival rates were 37.7%for ureteral cancer,25.5%for renal pelvic cancer,and 25.7%for bladder cancer.Further analysis revealed that the OS of the lesions originating from the bladder dome was significantly longer than that of the other bladder subgroups(P<0.05),while the OS of the lesions in bladder bottom was the shortest.The 2-year survival rates were 52.0%for the bladder dome,13.0%for the bladder body,and 10.7%for the bladder bottom.Conclusion Our study indicates that in the non-ICIs era,there was no significant difference in the prognosis among mUC patients with lesions from different primary sites.In the ICIs era,the OS of ureteral cancer was significantly longer than that of bladder cancer and renal pelvis cancer.As for patients with metastatic bladder cancer,those with tumor located at the top of the bladder had a significantly better prognosis than those with tumors at other sites.

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