ObjectiveTo investigate the mechanisms by which Liuwei Buqi prescription （LWBQ） regulates alveolar macrophage efferocytosis and improves inflammatory responses in rats with chronic obstructive pulmonary disease （COPD） characterized by lung-kidney Qi deficiency based on the nuclear factor erythroid 2-related factor 2 （Nrf2）/macrophage receptor with collagenous structure （MARCO） pathway. MethodsSuccessfully modeled rats were randomly divided into a model group， low-dose LWBQ group （LWBQ-L， 2.25 g·kg^-1·d^-1）， medium-dose LWBQ group （LWBQ-M， 4.5 g·kg^-1·d^-1）， high-dose LWBQ group （LWBQ-H， 9 g·kg^-1·d^-1）， and aminophylline group （AMIN， 50 mg·kg^-1·d^-1）， with 8 rats in each group. Another 8 healthy rats were included as the blank group. Except for the blank group， rats in the remaining groups were subjected to smoke exposure combined with forced swimming， intratracheal lipopolysaccharide （LPS） instillation， and subcutaneous hydrocortisone injection to establish a COPD model with lung-kidney Qi deficiency. After successful modeling， rats were administered different doses of LWBQ or AMIN by gavage. Body weight， fur condition， and oral secretions were observed. Pulmonary function was measured using an animal lung function analyzer. Enzyme-linked immunosorbent assay （ELISA） was used to detect the expression levels of interferon-γ （IFN-γ）， interleukin-6 （IL-6）， interleukin-1 （IL-1）， and tumor necrosis factor-α （TNF-α） in bronchoalveolar lavage fluid （BALF） and serum （SER）. Hematoxylin-eosin （HE） staining was used to examine pathological changes in lung tissue. Giemsa staining was performed to detect eosinophils， basophils， and neutrophils in BALF. Terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling （TUNEL） was used to detect apoptosis in lung tissue. Western blot and real-time polymerase chain reaction （Real-time PCR） were employed to determine the protein and mRNA expression levels of efferocytosis-related proteins growth arrest-specific gene 6 （GAS6）， milk fat globule-epidermal growth factor 8 （MFG-E8）， and pathway-related proteins Nrf2 and MARCO in lung tissue. ResultsCompared with the blank group， the model group showed reduced food intake， nasal and oral secretions with sputum， and decreased body weight （P<0.01）， decreased peak expiratory flow （PEF） （P<0.01）， increased forced vital capacity （FVC） （P<0.01）， and decreased forced expiratory volume in 0.3 s/forced vital capacity ［FEV0.3/FVC （%）］ （P<0.01）. The expression levels of IFN-γ， IL-6， IL-1， and TNF-α in BALF and SER were increased （P<0.01）. Lung tissue exhibited structural destruction， hyperplasia， inflammatory exudation， increased apoptotic cells， and increased mean optical density （P<0.01）. The protein and mRNA expression levels of GAS6， MFG-E8， and MARCO， as well as Nrf2 mRNA expression， were increased （P<0.01）. Compared with the model group， the LWBQ groups showed increased food intake， reduced nasal and oral secretions with sputum， and increased body weight （P<0.05， P<0.01）. PEF was increased （P<0.01）. FVC was increased in rats treated with low- and medium-dose LWBQ （P<0.01）， and FEV0.3/FVC （%） was increased in rats treated with medium- and high-dose LWBQ （P<0.05， P<0.01）. The expression levels of IFN-γ， IL-6， IL-1， and TNF-α in BALF and SER were decreased （P<0.01）. Lung tissue structure was relatively intact， with improvement in hyperplasia and inflammatory exudation. The number of apoptotic cells in lung tissue was reduced， and mean optical density was decreased （P<0.05， P<0.01）. The protein and mRNA expression levels of efferocytosis-related proteins GAS6 and MFG-E8 and pathway-related proteins Nrf2 and MARCO were increased （P<0.01）. ConclusionLWBQ can alleviate pulmonary and systemic inflammation， improve lung function， and reduce lung tissue damage in rats with COPD characterized by lung-kidney Qi deficiency. The mechanism may be related to enhancement of alveolar macrophage efferocytosis through regulation of the Nrf2/MARCO pathway.

OBJECTIVE: To investigate the effect and mechanism of Hyssopus cuspidatus Boriss. extract (HCE) in ovalbumin (OVA)-induced allergic asthma. METHODS: Components identification of HCE was conducted using ultra performance liquid chromatography-quadrupole-time of flight-mass spectrometry. Mice were sensitized with OVA to establish asthmatic model, and dexamethasone was used as positive control. Respiratory reactivity, white cells counting in bronchoalveolar lavage fluid and peripheral blood, cytokine level measurement in serum and lung tissue, and histologic examination were performed to evaluate the therapeutic effect of HCE on asthma. Network pharmacology approach was used for mechanism prediction. Western blotting and untargeted lipidomics method were applied for mechanism validation. RESULTS: Fifty-two compounds were identified in HCE, predominantly terpenoids and flavonoids. HCE markedly reduced airway resistance, the eosinophil infiltration in lung tissues, and the levels of immunoglobulin E, interleukin-4, interleukin-5, and interleukin-13. Network pharmacology analysis suggested phosphatidylinositol 3-kinases (PI3K), c-Jun N-terminal kinase (JNK), and p38 Mitogen-activated protein kinase (p38 MAPK) may be key proteins of HCE in the treatment of allergic asthma. Western blot results indicated that the levels of phosphorylated PI3K, JNK, and P38 were downregulated in HCE-treated group. Moreover, HCE significantly upregulated the levels of ceramide and sphingomyelin and downregulated the level of phosphatidylcholine. CONCLUSION HCE inhibited allergic asthma via PI3K/JNK/P38 signaling pathway and lipid homeostasis regulation.

Objective:To compare the efficacy of posteromedial combined with lateral Frosch approach versus anterior medial and lateral dual incision approach in open reduction and internal fixation for Schatzker type VI tibial plateau fractures.Methods:A retrospective cohort study was conducted to analyze the clinical data of 41 patients with Schatzker type VI tibial plateau fractures, who were admitted to the 940th Hospital of the Joint Logistics Support Force of the PLA from January 2018 to May 2024, including 23 males and 18 females, aged 34-79 years [(50.7±7.7)years]. Twenty-three patients underwent open reduction and internal fixation via the posteromedial combined with lateral Frosch approach (posterior approach group), while 18 patients underwent the same procedure via the anterior medial and lateral dual incision approach (anterior approach group). The following parameters were compared between the two groups: operation duration, intraoperative blood loss, postoperative drainage volume, depth of articular surface depression and tibial plateau width measured preoperatively, at 7 days, 3 months postoperatively, and at the last follow-up, medial proximal tibial angle (MPTA) and posterior proximal tibial angle (PPTA) measured at 7 days, 3 months postoperatively, and at the last follow-up, visual analogue scale (VAS) scores assessed preoperatively, at 7 days postoperatively, and at the last follow-up, American Knee Society (KSS) score and knee flexion range of motion assessed at 7 days, 3 months postoperatively, and at the last follow-up, fracture healing status at the last follow-up, and incidence of postoperative complications.Results:All the patients were followed up for 12-16 months [(14.3±2.1)months]. The operation duration was (119.6±11.8)minutes in the posterior approach group, which was significantly shorter than (140.3±10.6)minutes in the anterior approach group ( P<0.05). There were no statistically significant differences in intraoperative blood loss or postoperative drainage volume between the two groups ( P>0.05). No significant differences were found in the preoperative depth of articular surface depression or tibial plateau width between the two groups ( P>0.05). At 7 days, 3 months postoperatively, and at the last follow-up, the depth of articular surface depression was 0.8(0.6, 1.0)mm, 0.6(0.5, 0.8)mm, and 0.6(0.5, 0.7)mm in the posterior approach group, which were significantly shorter than 1.1(0.9, 1.3)mm, 0.8(0.7, 1.0)mm, and 0.8(0.7, 1.0)mm in the anterior approach group ( P<0.05). The tibial plateau width at the same time points was 71.0(69.1, 73.5)mm, 70.5(69.2, 72.9)mm, and 70.5(69.3, 72.5)mm in the posterior approach group, which were significantly shorter than 73.0(72.3, 74.2)mm, 71.5(71.0, 73.0)mm, and 71.5(71.1, 72.6)mm in the anterior approach group ( P<0.05). At 7 days, 3 months postoperatively, and at the last follow-up, the MPTA values were (87.4±0.7)°, (87.7±0.6)°, and (87.9±0.5)° in the posterior approach group, which were significantly larger than (85.2±2.5)°, (86.0±2.2)°, and (86.3±2.0)° in the anterior approach group ( P<0.01). The PPTA values at the same time points were (9.5±0.7)°, (9.0±0.5)°, and (8.6±0.4)° in the posterior approach group, which were significantly smaller than (11.2±1.0)°, (10.3±0.8)°, and (9.8±0.7)° in the anterior approach group ( P<0.01). There was no significant difference in the preoperative VAS score between the two groups ( P>0.05). At 7 days postoperatively and at the last follow-up, the VAS scores were 4.0(3.0, 5.0)points and 0.5(0.0, 2.0)points in the posterior approach group, which were significantly lower than 5.0(4.0, 5.0)points and 1.0(1.0, 3.0)points in the anterior approach group ( P<0.05). At 7 days, 3 months postoperatively, and at the last follow-up, the KSS scores were 62.5(57.0, 67.5)points, 75.5(72.0, 82.5)points, and 87.0(82.5, 93.5)points in the posterior approach group, which were significantly higher than 61.5(54.5, 63.0)points, 74.0(68.0, 79.0)points, and 85.5(78.0, 88.5)points in the anterior approach group ( P<0.05). The knee flexion range of motion was 90.0(85.0, 95.0)°, 115.0(109.0, 122.0)°, and 126.0(120.0, 130.0)° in the posterior approach group, which were significantly greater than 80.5(75.2, 85.8)°, 110.0(104.0, 115.0)°, and 119.0(113.0, 122.0)° in the anterior approach group ( P<0.05). At the last follow-up, all the fractures were healed in both groups. No statistically significant difference was found in the incidence of postoperative complications between the two groups ( P>0.05). Conclusion:Compared to the anterior medial and lateral dual incision approach, the posteromedial combined with lateral Frosch approach demonstrates superior advantages in operation duration, reduction quality, pain relief, functional recovery in the treatment of Schatzker type VI tibial plateau fractures, while the incidence of complications is comparable.

[Objective]To explore and discuss the mechanism of ZHANG Zhongjing's methods of wind medicine in treating delayed-pulse heart disease by applying the theory of wind medicine in Neijing and the understanding of wind medicine by medical practitioners throughout the history.[Methods]Summarize ZHANG Zhongjing's compilation of Treatise on Febrile Diseases and Synopsis of the Golden Chamber,explore the etiology and pathogenesis of delayed-pulse heart disease,as well as the mechanism of wind medicine for restoring meridians,and use modern pharmacological research to demonstrate the effective ingredient targets of wind medicine.[Results]It was found that the causes of wind-induced delayed-pulse included external wind evil,internal liver wind,wind damaging heart Qi and evil obstructing heart meridians which were its basic pathogenesis.The treatment methods of tonifying the heart and supporting the essence,dispelling wind and unblocking the meridians were the main methods.Based on this,a wind medicine complex pulse treatment method was established,and Zhongjing's differentiation and medication were classified into 9 types and 9 methods,forming a series of treatment frameworks,including:regulating and tonifying the Ying Wei,dispelling wind and dispelling evil,clearing upper and warming lower,dispelling wind and dispersing toxins,nourishing Qi and blood,dispelling wind and removing Bi,unblocking Yang and dispersing cold,calming the Ying Wei,resolving phlegm and promoting stagnation,promoting Bi and unblocking the meridians,promoting and clearing spleen,invigorating Qi for relieving desertion,warming kidney and nourishing essence,stimulating Wei Qi,promoting lung and strengthening heart,warming water and drinking method,dispelling wind and unblocking meridians,promoting blood circulation and removing stasis.Furthermore,the mechanism of action of wind medicine in restoring meridians was analyzed,including expelling external wind,relieving liver and dispelling wind,harmonizing Yin and Wei,promoting spleen and clearing blood,resolving phlegm and dampness,promoting blood circulation and unblocking collaterals,nourishing blood,and calming the heart and mind.This was confirmed to be consistent with the effective ingredient targets of modern pharmacological research on wind medicine.[Conclusion]The Zhongjing wind herbal pulse restoration method has significant theoretical guidance and clinical application value in the diagnosis and treatment of refractory bradycardia.

Objective:To compare the efficacy of early versus delayed reconstruction of anterior cruciate ligament (ACL) ruptures under arthroscopy.Methods:A retrospective cohort study was conducted to analyze the clinical data of 260 young adults with ACL ruptures admitted to 940th Hospital of Joint Logistic Support Force of PLA from January 2022 to June 2024, including 171 males and 89 females, aged 18-45 years [(25.6±5.9)years]. Left knee was involved in 127 patients, while the right in 133 patients. All the patients underwent arthroscopic ACL reconstruction with autologous tendon grafts, of whom 130 patients were treated within 3 months after injury (early reconstruction group) but other 130 treated at 3 months after injury (delayed reconstruction group). The operative duration and intraoperative bleeding were compared between the two groups. The incidence of medial meniscus (MM) and lateral meniscus (LM) tears and the incidence of corresponding types of tears were recorded intraoperatively in the two groups. Tegner score and Lysholm score preoperatively, at 3 months postoperatively, and at the last follow-up were detected. Visual analogue scale (VAS) scores at 3 months postoperatively and at the last follow-up and postoperative complication rate were compared between the two groups.Results:All the patients were followed up for 6-15 months [(9.1±3.2)months]. There were no significant differences in operative duration or intraoperative bleeding between the two groups ( P>0.05). The incidence of MM tears in the early reconstruction group was 22.3% (29/130), lower than 34.6% (45/130) in the delayed reconstruction group ( P<0.05). There was no significant difference in the incidence of LM tears between the two groups ( P>0.05). The incidence of MM bucket-handle tears in the early reconstruction group was 2.3% (3/130), lower than 9.2% (12/130) in the delayed reconstruction group ( P<0.05), while no significant difference in the incidence of other types of meniscus tears was found between the two groups ( P>0.05). There were no significant differences in Tegner score or Lysholm score preoperatively between the two groups ( P>0.05). At 3 months postoperatively and at the last follow-up, the Tegner scores in the early reconstruction group were (7.4±1.3)points and (8.6±0.7)points, higher than (6.4±1.5)points and (7.9±0.6)points in the delayed reconstruction group and the Lysholm scores were (82.1±7.1)points and (90.7±3.8)points in the early reconstruction group, higher than (79.5±6.8)points and (86.3±4.0)points in the delayed reconstruction group ( P<0.01). There were no significant differences in VAS scores between the two groups at 3 months postoperatively or at the last follow-up ( P>0.05). The postoperative complication rate was 8.5% (11/130) in the early reconstruction group and 12.3% (16/130) in the delayed reconstruction group ( P>0.05). Conclusion:For young patients with ACL rupture, arthroscopic reconstruction within 3 months after injury can reduce the incidence of MM tear and bucket-handle tear and improve knee function without increasing the incidence of other complications when compared with delayed reconstruction at 3 months after injury.

ObjectiveThis paper used the AGREE Ⅱ guideline evaluation tool to evaluate the quality of 14 clinical guidelines for acute myocardial infarction，aiming to provide reference for the formulation and improvement of the guidelines. MethodsClinical guidelines and expert consensus related to acute myocardial infarction were searched by web search. The search period ranges from January 1，2019 to November 1，2024 in CNKI，VIP，Wanfang Data，SinoMed，Web of Science，OVID， the International Guidelines Collaboration Network （GIN），the UK National Institute for Health and Clinical Excellence （NICE），Yimaitong， and other platforms. Three researchers independently screened the literature and used AGREE Ⅱ to score the screening results. After ensuring that the researchers have a consistent understanding of each guideline，the quality of the guidelines was evaluated. After that，the ratings were analyzed by layer according to the issuing agency，category，method of formulation，and funding situation and compared longitudinally by rating time. The clinical guidelines and expert consensus were compared in terms of content and evidence. ResultsA total of 14 guidelines and consensus were included. The results of AGREE Ⅱ in the six areas in descending order were scope and purpose （62.82%±10.43%），rigor （62.40%±12.77%），editorial independence （62.11%±22.26%），participants （61.42%±11.65%），clarity of expression （59.98%±9.62%），and application （52.94%±16.90%） . Eleven of the guidelines were at level B， and three were at level A. In the stratified analysis，the score of the guideline formulated by the Chinese Medical Doctor Association was lower. There was little difference between the scores of Chinese/Western and Western medicine guidelines. The average score of the guidelines was higher than the consensus. Funded guidelines and consensus scores were higher. In the longitudinal comparison，the highest number of guidelines were developed in 2020 and 2021，while those developed in 2023 scored the highest. In the differential comparison analysis，the content of the guidelines was more comprehensive， and the evidence level was higher，while the content of the consensus was more novel， and the evidence was less. ConclusionThe AGREE Ⅱ score of the clinical guidelines for acute myocardial infarction is generally moderate，and there is room for improvement in terms of applicability. At the same time，the content quality of expert consensus should be improved，and more efforts should be made to develop and apply Chinese medicine guidelines for complications such as heart failure and microcirculatory obstruction after acute myocardial infarction.

Objective To analyze the detrimental effects of exposure to environmental noise alone and combined with carbon monoxide(CO)on spermatogenesis in male rats,investigate the underlying mechanisms involved in such damage,and evaluate the protective role of pterostilbene(PTE)against these adverse effects.Methods Sixty male SD rats(6～8 weeks old,weighing 200±10 g)were randomly divided normal control group(standard housing),sham-exposure control group(restraint stress only),noise exposure(85 dB),CO exposure(460 mg/m3),combined exposure(simultaneous exposure),and PTE intervention(80 mg/kg pretreatment),with 10 animals in each group.The rats were exposed daily for 2 h via a nose-only inhalation exposure system within a multifactorial environmental simulation chamber for 60 consecutive days.Sperm count and viability were measured after exposure.Histopathological changes of testicular tissues were observed with HE staining.qRT-PCR was used to measure stage-specific mRNA levels in germ cells.Serum sex hormone levels and adenosine triphosphate(ATP)concentrations in testes and sperm were detected.Transmission electron microscopy(TEM)was applied to observe the ultrastructural damage in the spermatocytes.Additionally,transcriptome sequencing was performed on testicular tissue,followed by bioinformatics analysis.Results Compared with the negative control group,the combined exposure group exhibited significant reductions in sperm viability and count(P<0.05),and developmental arrest of immature germ cells in the testicular tissue,with obviously less spermatogonia,spermatocytes,and round/elongated spermatids(P<0.01).Additionally,significantly reduced levels of reproductive-related hormones,such as gonadotropin-releasing hormone,follicle-stimulating hormone,luteinizing hormone and testosterone,and ATP levels in testes and sperm were observed in the mice after combined exposure(P<0.01),accompanied by mitochondrial rupture and cristae disruption in spermatocytes.Conversely,the PTE intervention group showed marked alleviation of these impairments,with parameters recovering almost to normal levels.Transcriptome sequencing identified biological processes related to reproductive development and ATP-dependent pathways as potential contributors to testicular injury induced by noise and CO exposure,with key genes including Nppa,Adm,Gnrh1,Ptafr,Atp13a5,Atp8b1,and LOC102555469.Conclusion Noise and CO exposure induce spermatogenic damage in rats,which may be related with energy metabolism and hormonal regulation,while PTE demonstrates significant protective effects against such reproductive impairments.

Objective To investigate the transgenerational effects of paternal PM2.5 exposure on offspring growth and development,and to preliminarily elucidate the role of sperm DNA methylation modifications in mediating these effects.Methods Eight-week-old male C57BL/6 mice were randomly divided into filtered air(FA),unfiltered air(UA),and concentrated PM2.5(CAP)groups,with 10 animals in each group.The exposure was conducted from November 2019 to April 2020,and then,these male mice were mated with unexposed females to generate F1 offspring,which were bred successively to produce F2 and F3 generations.All the offspring were living in PM2.5-free environment.The birth body weight,birth number,and sex ratio of the offspring were recorded,body weight growth was monitored,and organ coefficients of the heart,liver,lung,and brain were calculated.Whole-genome methylation sequencing was performed on the sperm DNA of the CAP group,FA group,and their F1 generation offspring to screen for differentially methylated regions,and the genes and pathways associated with these regions were analyzed.Results When compared with the F1～F3 offspring of the FA group,the CAP group had significantly reduced birth body weight in the F1 generation(P<0.05),no statistical differences were observed in the birth body weight in the F2 and F3 generations(P>0.05),or either in the sex ratio and birth number among the F1,F2 and F3 generations.Compared with the FA group offspring,the F1～F3 offspring of CAP group exhibited delayed body weight gain,especially in the males(P<0.05),the CAP-F1 male generation had obviously elevated liver organ coefficient(P<0.01),but no statistical changes were observed in the heart,lung,or brain coefficients among the F1～F3 generations.Between the FA group and the CAP group,37 997 differentially methylated regions were detected,with a reduction of approximately 50%in the number of differentially methylated regions in the F1 generation.Differentially methylated genes in F0 and F1 sperm were potentially related to developmental processes,including imprinting genes(Gnas,Igf2)and metabolic genes(Ppard,Rps6kb1).Conclusion Paternal exposure to PM2.5 leads to reduced birth weight and intergenerational growth retardation in offspring.Its impact on phenotypic effects is gradually weakened during intergenerational transmission.Changes in the methylation of development-related genes in sperm may be one of the mechanisms mediating this intergenerational effect.

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.

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.