177Lu-prostate specific membrane antigen(PSMA)radio-ligand therapy has been approved abroad for advanced prostate cancer and has been in several clinical trials in China.Based on domestic clinical practice and experimental data and referred to international experience and viewpoints,the expert group forms a consensus on the clinical application of 177Lu-PSMA radio-ligand therapy in prostate cancer to guide clinical practice.

ABSTRCT Purpose To explore the evolution of HER2 nega-tive subgroups(IHC Null,Ultra-low and 1+)in breast cancer with hormone receptor(HR)positive before and after neoadju-vant therapy,and the relationship with clinical pathological fea-tures.Methods There were 255 patients who did not achieve pathological complete response(pCR)consecutively after neoad-juvant therapy.Immunohistochemistry was used to detect the ex-pression of ER,PR,HER2 and Ki67 and to evaluate the evolu-tion of HER2-negative subgroups after neoadjuvant therapy and its relationship with clinicopathological characteristics.Results Among the 255 patients included in this study,HER2 expression was 0 and 1+in 116 cases(45.5％)and 139 cases(54.7％)respectively before neoadjuvant therapy,and then HER2 0 was further divided into Null group(61 cases,23.9％)and Ultra-low group(55 cases,21.6％).After neoadjuvant therapy,HER2 expression was 0 and 1+in 117 cases(45.9％)and 138 cases(54.1％)respectively,and then HER2 0 was further di-vided into Null group(64 cases,25.1％)and Ultra-low group(53 cases,20.8％).HER2 status changed in 121 patients(47.5％)after neoadjuvant therapy.The highest conversion rate was from HER2 Ultra-low before neoadjuvant therapy to 1+after neoadjuvant therapy,with a conversion rate of 11.76％(30/255),followed by HER2 1+to the Ultra-low,with a conversion rate of 10.98％(28/255).After the neoadjuvant therapy,44 of 55 cases had transformation in the HER2 Ultra-low group,with the conversion rate of as high as 80％.Chi-square test showed that HER2 expression before neoadjuvant therapy was correlated with the maximum tumor diameter(≤2 cm,＞2cm)after neo-adjuvant therapy(x2=6.106,P=0.047);the tumor of HER21+before neoadjuvant therapy was mostly 2 cm or less in the di-ameter.The HER2 status after neoadjuvant therapy was correla-ted with the tumor thrombus(x2=6.975,P=0.029).Patients with HER2 Ultra-low after treatment were more likely to have vascular invasion.Conclusion In HR positive breast cancer,when the HER2 0 cases are divided into Ultra-low and Null sub-groups,the HER2 conversion rate increases significantly after neoadjuvant therapy,in which the Ultra-low conversion rate is the highest,indicating that the HER2 Ultra-low cases are highly unstable after neoadjuvant therapy.It is important to detect HER2 expression in residual lesions after neoadjuvant therapy and to identify the Ultra-low HER2 expression subgroup.

Objective To explore the influencing factors of the efficacy of programmed death-1(PD-1)inhibitor pembrolizumab in the treatment of cervical cancer.Methods The clinical data of cervical cancer patients admitted to the Department of Obstetrics and Gynecology of Anhui Women and Children's Medical Center from January 2020 to October 2023 were retrospectively analyzed and the patients were divided into the ineffective group and the effective group according to the pembrolizumab treatment efficacy.The clinical data of patients in the two groups were compared[age,tumor type,pathological type,lesion size,differentiation degree,number of pregnancies,number of births,number of miscarriages,menopausal status,tumor mutation load(TMB),DNA repair gene mutation status,PD-L1 expression,diabetes mellitus,hypertension,mode of treatment,body mass index,tumor-infiltrating lymphocyte(TIL)expression,neoantigen intra-tumor heterogeneity(ITH)status,presence of liver disease,and family history],and logistic regression analysis was used to determine the risk factors affecting the efficacy of pembrolizumab in cervical cancer patients.Results A total of 60 patients were included in the study,with 42 in the effective group and 18 in the ineffective group.The proportion of patients with TMB＜143/Mb,no mutation in DNA repair genes,low expression of PD-L1,simple immunotherapy,TIL negative,and high PTH in the ineffective group was higher than that in the effective group(P＜0.05).Multivariate Logistic regression analysis showed that TMB＜143/Mb,non-mutated DNA repair genes,low PD-L1 expression,simple immunotherapy,TIL negative,and high PTH were risk factors affecting the efficacy of pembrolizumab in cervical cancer patients(P＜0.05).Conclusion The efficacy of the PD-1 inhibitor pembrolizumab in cervical cancer patients is influenced by factors such as TMB,DNA gene mutations,PD-L1 expression,treatment mode,TIL,and ETH.

OBJECTIVES: Spinal cord ischemia-reperfusion injury (SCIRI) remains a major challenge in the field of organ protection due to the lack of effective prevention and therapeutic strategies. Hyperglycemia, a common perioperative condition, contributes to neurological injury via multiple mechanisms. However, its role and underlying mechanism in SCIRI are still unclear. This study aims to investigate the involvement of the precursor of brain-derived neurotrophic factor (proBDNF) in hyperglycemia-induced SCIRI in mice. METHODS: Eight-week-old male C57BL/6 mice were randomly assigned to a control group (Vehicle) or a diabetes mellitus (DM) group. The DM group was established using intraperitoneal injection of streptozotocin (STZ) combined with 10% sucrose water. The Vehicle group received an equal volume of 50 mmol/L sodium citrate buffer (pH 4.5). Fasting blood-glucose levels ≥11.1 mmol/L were considered successful DM modeling. Both Vehicle and DM groups underwent SCIRI modeling via descending aortic clamping, while the Sham group underwent a sham procedure without aortic occlusion. Lower limb motor function was assessed using the Basso Mouse Scale (BMS) and its subscale (sub-BMS). Locomotor activity was evaluated using an open field test. Immunohistochemistry was performed to detect changes in neuronal nuclear protein (NeuN) and proBDNF expression in spinal cord tissues. Real-time reverse transcription polymerase chain reaction (RT-PCR) was used to measure mRNA expression of interleukin-1β (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α). To explore the effect of proBDNF inhibition, diabetic mice were divided into groups: A DM+SCIRI+monoclonal anti-proBDNF antibody (McAb-proB) group received an intraperitoneal injection of 100 μg of McAb-proB 30 minutes before SCIRI modeling, and a DM+SCIRI+Vehicle group received an equal amount of isotype immunoglobulin G. BMS and sub-BMS scores were recorded, and the gene expression of inflammatory cytokines mentioned above were evaluated. RESULTS: Compared with the Vehicle+SCIRI group, the DM+SCIRI group showed significantly reduced BMS and sub-BMS scores, decreased NeuN expression, shorter total movement distance, slower locomotion, increased proBDNF expression, and elevated IL-1β, IL-6, and TNF-α mRNA levels (all P<0.05 or P<0.01). Compared with the DM+SCIRI+Vehicle group, the DM+SCIRI+McAb-proB group exhibited significantly improved BMS and sub-BMS scores and decreased mRNA expression of IL-1β, IL-6, and TNF-α (all P<0.05 or P<0.01). CONCLUSIONS Hyperglycemia exacerbates neural injury and inflammatory response in SCIRI through upregulation of proBDNF expression, delaying motor functional recovery. Antagonizing proBDNF expression can alleviate neurological damage and promote functional recovery in diabetic mice after SCIRI.
Animals ; Male ; Hyperglycemia/metabolism* ; Brain-Derived Neurotrophic Factor/genetics* ; Mice, Inbred C57BL ; Reperfusion Injury/metabolism* ; Mice ; Diabetes Mellitus, Experimental/metabolism* ; Inflammation/metabolism* ; Disease Models, Animal ; Spinal Cord/metabolism* ; Tumor Necrosis Factor-alpha/metabolism* ; Protein Precursors/genetics* ; Spinal Cord Ischemia/metabolism* ; Interleukin-6/metabolism* ; Interleukin-1beta/metabolism*

Objective:Explore the relationship between sleep duration, sleep time and brachial-ankle pulse wave velocity(baPWV) in community population.Methods:Questionnaire, physical examination, blood tests, and baPWV detection were applied to a community based population. Finally, 3 912 subjects with complete data were included in the study. The relationship between sleep duration, time to fall asleep and PWV was evaluated with binary logistic regression analysis. Results:Being adjusted for age, sex, prevalence of diabetes, sleep condition, body mass index, blood glucose, blood pressure, dyslipidemia, ankle-brachial index, sleep duration and time to fall asleep were correlated with PWV. The risk of PWV abnormalities was increased in the≥8 h group compared to the 6-8 h group( OR=1.155, 95% CI 0.995-1.367, P=0.037). The risk of abnormalities PWV was higher in the group with sleep time after 00: 00 than in the group -23: 00( OR=1.482, 95% CI 1.008-2.179, P=0.045). Conclusion:Long sleep duration(≥8 h) and late sleep time(after 00: 00) may be associated with higher risk of atherosclerosis.

Background::Although existing mycological tests (bronchoalveolar lavage [BAL] galactomannan [GM], serum GM, serum (1,3)-β-D-glucan [BDG], and fungal culture) are widely used for diagnosing invasive pulmonary aspergillosis (IPA) in non-hematological patients with respiratory diseases, their clinical utility in this large population is actually unclear. We aimed to resolve this clinical uncertainty by evaluating the diagnostic accuracy and utility of existing tests and explore the efficacy of novel sputum-based Aspergillus assays. Methods::Existing tests were assessed in a prospective and consecutive cohort of patients with respiratory diseases in West China Hospital between 2016 and 2019 while novel sputum assays (especially sputum GM and Aspergillus-specific lateral-flow device [LFD]) in a case-controlled subcohort. IPA was defined according to the modified European Organization for Research and Treatment of Cancer/Mycoses Study Group criteria. Sensitivity and specificity were computed for each test and receiver operating characteristic (ROC) curve analysis was performed. Results::The entire cohort included 3530 admissions (proven/probable IPA = 66, no IPA = 3464) and the subcohort included 127 admissions (proven/probable IPA = 38, no IPA = 89). Sensitivity of BAL GM (≥1.0 optical density index [ODI]: 86% [24/28]) was substantially higher than that of serum GM (≥0.5 ODI: 38% [39/102]) ( χ2 = 19.83, P < 0.001), serum BDG (≥70 pg/mL: 33% [31/95]) ( χ2 = 24.65, P < 0.001), and fungal culture (33% [84/253]) ( χ2 = 29.38, P < 0.001). Specificity varied between BAL GM (≥1.0 ODI: 94% [377/402]), serum GM (≥0.5 ODI: 95% [2130/2248]), BDG (89% [1878/2106]), and culture (98% [4936/5055]). Sputum GM (≥2.0 ODI) had similar sensitivity (84% [32/38]) (Fisher’s exact P = 1.000) to and slightly lower specificity (87% [77/89]) ( χ2 = 5.52, P = 0.019) than BAL GM (≥1.0 ODI). Area under the ROC curve values were comparable between sputum GM (0.883 [0.812-0.953]) and BAL GM (0.901 [0.824-0.977]) ( P = 0.734). Sputum LFD had similar specificity (91% [81/89]) ( χ2 = 0.89, P = 0.345) to and lower sensitivity (63% [24/38]) ( χ2 = 4.14, P = 0.042) than BAL GM (≥1.0 ODI), but significantly higher sensitivity than serum GM (≥0.5 ODI) ( χ2 = 6.95, P = 0.008), BDG ( χ2 = 10.43, P = 0.001), and fungal culture ( χ2 = 12.70, P < 0.001). Conclusions::Serum GM, serum BDG, and fungal culture lack sufficient sensitivity for diagnosing IPA in respiratory patients. Sputum GM and LFD assays hold promise as rapid, sensitive, and non-invasive alternatives to the BAL GM test.

Objective:To explore the relationship between famine exposure in early life and bone mineral density measured by ultrasound in postmenopausal women.Methods:From May 2011 to October 2011, 10 140 residents over 40 years old in Yunyan District of Guiyang City were randomly selected, and followed up for 3 years, 7 493 subjects were selected and finally included a total of 1 504 subjects. Grouped by date of birth, the differences in bone mineral density measured by ultrasound, and risk of osteoporosis between the exposed and non-exposed groups were compared.Results:SOS, T-score, and QUI in infant- and preschool-exposed group were lower than those of non-exposed group. The medium/high risk of osteoporosis in non-exposed, fetal-exposed, infant-exposed, and preschool-exposed groups were 50%, 46.8%, 58.4%, and 62.8%, respectively ( P<0.01). Multivariate linear regression analysis showed that famine exposure in infant- and preschool-exposed groups were significantly negative correlated with SOS, T-score, and QUI, while fetal-exposed group was not significantly correlated with SOS, T-score, and QUI. Compared with the non-exposed group, the OR of the medium/high risk of osteoporosis in the infant- and preschool-exposed groups were( OR=1.41, 95% CI 1.02-1.96)、( OR=1.68, 95% CI 1.21-2.34), with statistically significance ( P<0.05), and there was no statistical significance in the fetal-exposed group. After adjusting for confounding factors, the medium/high risk of osteoporosis in infant- and preschool-exposed group were 1.64 and 1.90 as compared with the non-exposed group ( OR=1.64, 95% CI 1.16-2.32, P<0.05 and OR=1.90, 95% CI 1.35-2.70, P<0.05). Conclusion:In postmenopausal women, famine exposure in early life was significantly negatively correlated with bone mineral density measured by ultrasound (SOS, T-score, and QUI), and was associated with an increased risk of osteoporosis.

Objective To analyze the clinical features and prognosis of patients with infective endocarditis(IE) and acute kidney injury(AKI),and to evaluate the effect of timely operation on prognosis of renal function.MethodsClinical data of 45 IE and AKI cases in Peking Union Medical College Hospital from January 2010 to May 2016 were retrospectively reviewed;among them 8 cases underwent renal biopsy and the pathologies were analyzed.Patients were divided into Operation group(22 cases) and Non-operation group(23 cases),the clinical data and prognosis were compared.Results The ratio of male to female was 2.46:1 and the average age was 48.3±16.6.35.6% of cases were found with basic valve diseases,the congenital valve diseases were the most common type.The most frequently infected valves were mitral valve(46.7%),aortic valve(28.9%) and prosthetic valve(8.9%) ordinally.The most common pathogenic bacteria were streptococcus(46.7%) and staphylococcus(35.6%).Some rare and special pathogen could also be found in these cases.In 8 cases underwent renal biopsy,3 cases were diagnosed as crescentic nephritis,2 cases were diagnosed as focal proliferative glomerulone-phritis and mesangial prolif-erative glomerulonephritis respectively,1 case was diagnosed as acute interstitial nephritis.C3 sedimentation was the most common phenomenon found in immunofluorescence.There was no significant difference between the baseline data of Operation and Non-operation groups,and neither was the survival rate.However,renal function recovered better in Operation group(P<0.05): the serum creatinine declined remarkably in 7 days(P<0.05) and 30 days(P<0.01)post operation,compared with the peak valve before operation.Conclusions The underline valve diseases and pathogen have been changed in IE as compared with traditional description.Crescentic nephritis is common in renal pathologic manifestation when parenchymal lesion is developed after the onset of IE.Timely operation can improve the renal prognosis in patients with IE and AKI.

Objective To investigate the effect of visual management on the prevention of nosocomial infection for the patients in hospital in the department of gynecology and obstetrics.Methods Three hundred and sixteen in-patients who were treated in the department of obstetrics and gynecology in our hospital from July 2013 to June 2014 were included in the control group. The routine prevention infection management was used in the control group. Three hundred and twenty-five in-patients who were treated in the department of obstetrics and gynecology in our hospital from October 2014 to September 2015 were included in the observation group. The visual management was used to prevent infection in the observation group. Hospital infection,infection site,length of hospital stay and patients' satisfaction were compared between the two groups.Results There were 22 cases of hospital infection in the two groups,including 5 cases in the observation group and 17 cases in the control group. The difference between the two groups was statistically significant (x2=8.532,P<0.01). In the observation group, the infection rate of infection sites of the patients was significantly lower compared with the patients in the control group (P<0.05). In the observation group,the average hospitalization time was (6.2±1.6) d,which was significantly shorter compared with the patients in the control group (8.6±2.1) d (t=3.26, P=0.001). The total satisfaction in the observation group was 100.0%,which was significantly different from that in the control group (89.6%) (x2=7.814,P<0.05).Conclusions The implementation of visual management to prevent infection in the patients of the department of gynecology and obstetrics can reduce the infection rate of patients,shorten their hospitalization time and improve patients'satisfaction of the intervention.

Objective To investigate the incidence of thyroid space occupying lesion by ultrasound imaging in patients with breast cancer.Methods From 2009 to 2012,150 patients with breast cancer as experimental group and another 150 patients with breast benign diseases as control group underwent thyroid ultrasound examination.Ultrasound results of the two groups were analyzed to find the differences.Restult More obvious space occupying lesions were found in experimental group than those in control group (P＜0.05).Conclusion The incidence rate of thyroid space occupying lesion in the patients with breast cancer is higher than that in the patients with no breast cancer.