As a practical carrier for promoting the tiered diagnosis and treatment model, the medical consor-tium is of great significance for balancing medical resources and boosting medical service efficiency. The construction of medical consortiums not only improves the accessibility of high-quality medical resources for patients, but also enhances the diagnostic and treatment level of member units. Meanwhile, it provides space for the leading hospital to adjust the structure of diseases and improve the level of discipline construction. As the core of medical insurance payment reform, DRG, through indicators such as the case mix index(CMI) and the number of diagnosis related group (DRG), provides objective and quantified data support for case management and disease structure optimization, thus effectively guiding the rational allocation of medical resources and the adjustmentof diseases and surgical types within the medical consortium. Comprehensive use of DRG evaluation indicators can construct a multidimensional medical consortium construction evaluation system, provides a clear direction for medical consortium cooperation, thereby promoting the overall healthy and sustainable development of medical consortiums and achieving a win-win situation for all parties involved. This paper, based on the "1+5+1" medical consortium cooperation model centered around Peking Union Medical College Hospital, utilizes DRG indicators to analyze the benefits for patients, member hospitals, and the leading hospital during the medical consortium construction process, with the hope of providing reference for the construction of a medical consortium evaluation system.

Objective To investigate the value of 18F labeled prostate-specific membrane antigen(18F-PSMA)-1007 developing agent PET/CT(18F-PSMA-1007PET/CT)examination in the diagnostic evaluation and therapeutic decision of the newly diagnosed prostate cancer(PCa)and follow up after radical prostatecto-my(RP).Methods This study adopted the retrospective observational study method.A total of 68 patients receiving 18 F-PSMA-1007 PET/CT examination in this hospital from September 2022 to October 2023 were analyzed,including 36 cases of newly diagnosed PCa and 32 cases of biochemistry follow up failure after RP.A total of 30 items of clinical data were collected,including 8 items of basic clinical characteristics,7 items of pa-thology-related characteristics and 15 items of imaging characteristics.The patients clinical characteristics in the newly diagnosed PCa and biochemical failure after RP conducted the descriptive analysis.The Fisher exact probability method was used to analyze the differentiation of the SUVmax of primary lesions in different clini-cal subgroups[different tPSA levels at diagnosis,different mi-T stages,different Gleason scores at postopera-tive pathological puncture and different pathological types]in the newly diagnosed PCa group and the differ-entiation of recurrent lesion detection rates in different clinical subgroups(different tPSA in 18F-PSMA-1007 PET/CT examination,different pathological T stages,different lymph node invasion and different pathological Gleason scores in the biochemical failure after RP group.The Spearman correlation was adopted to test and analyze the correlation between the imaging features of positive lesions and tPSA.Results In the newly diag-nosed PCa group,there were 1 case of prostatic hyperplasia and 35 cases of PCa.SUVmax had no statistical differences among the primary lesions with different tPSA levels(P=0.81),different mi-T stages(P=0.70),different puncture Glleasonscores(P=0.20)and different pathological types(P=0.71).Moreover the tPSA value at diagnosis was positively correlated with the number of metastatic lesions(r=0.410,P=0.01).The clinical treatment decisions in 11 cases(31.43％)were changed according to the examination re-sults.In 9 cases of RP combined with lymph node dissection,the accuracy rate and concordance rate of 18F-PS-MA-1007 PET/CT and MRI in the lymph node detection rate all were 100％.I n the biochemical failure after RP group,the overall recurrent lesion detection rate was 71.88％(23/32),the operative area in situ recurrence(11 cases,34.38％)and bone metastasis(11 cases,34.38％)were most common.The differences of 18F-PS-MA-1007 PET/CT recurrent lesions detection rates had no statistical differences among the patients with dif-ferent tPSA levels(P=0.08),different pathological T stages(P=0.10),different postoperative pathological lymph node invasions(P=0.68)and different pathologic Gleason score in the 18F-PSMA-1007 PET/CT ex-amination.In the 18 F-PSMA-1007 PET/CT examination in the biochemical failure after RP,the tPSA value in the recurrent lesion was positively correlated with the number of recurrent lesions(r=0.48,P=0.01),SUVmax value in the recurrent lesion(r=0.46,P=0.01)and the SUVmean value(r=0.38,P=0.03).The clinical treatment decision in 18 cases(56.25％)was changed according to the examination results.Conclusion 18 F-PSMA-1007 PET/CT has good diagnostic value and efficiency for primary lesion and metastasis lesion of new-ly diagnosed PCa and recurrent foci of biochemical failure after RP.

Male ; Humans ; Aged ; Sleep Duration ; Aging ; Testosterone ; China ; Sleep

Peptide‒drug conjugates (PDCs) are drug delivery systems consisting of a drug covalently coupled to a multifunctional peptide via a cleavable linker. As an emerging prodrug strategy, PDCs not only preserve the function and bioactivity of the peptides but also release the drugs responsively with the cleavable property of the linkers. Given the ability to significantly improve the circulation stability and targeting of drugs in vivo and reduce the toxic side effects of drugs, PDCs have already been extensively applied in drug delivery. Herein, we review the types and mechanisms of peptides, linkers and drugs used to construct PDCs, and summarize the clinical applications and challenges of PDC drugs.

LIN28 is an RNA binding protein with important roles in early embryo development, stem cell differentiation/reprogramming, tumorigenesis and metabolism. Previous studies have focused mainly on its role in the cytosol where it interacts with Let-7 microRNA precursors or mRNAs, and few have addressed LIN28's role within the nucleus. Here, we show that LIN28 displays dynamic temporal and spatial expression during murine embryo development. Maternal LIN28 expression drops upon exit from the 2-cell stage, and zygotic LIN28 protein is induced at the forming nucleolus during 4-cell to blastocyst stage development, to become dominantly expressed in the cytosol after implantation. In cultured pluripotent stem cells (PSCs), loss of LIN28 led to nucleolar stress and activation of a 2-cell/4-cell-like transcriptional program characterized by the expression of endogenous retrovirus genes. Mechanistically, LIN28 binds to small nucleolar RNAs and rRNA to maintain nucleolar integrity, and its loss leads to nucleolar phase separation defects, ribosomal stress and activation of P53 which in turn binds to and activates 2C transcription factor Dux. LIN28 also resides in a complex containing the nucleolar factor Nucleolin (NCL) and the transcriptional repressor TRIM28, and LIN28 loss leads to reduced occupancy of the NCL/TRIM28 complex on the Dux and rDNA loci, and thus de-repressed Dux and reduced rRNA expression. Lin28 knockout cells with nucleolar stress are more likely to assume a slowly cycling, translationally inert and anabolically inactive state, which is a part of previously unappreciated 2C-like transcriptional program. These findings elucidate novel roles for nucleolar LIN28 in PSCs, and a new mechanism linking 2C program and nucleolar functions in PSCs and early embryo development.
Animals ; Cell Differentiation ; Embryo, Mammalian/metabolism* ; Embryonic Development ; Mice ; Pluripotent Stem Cells/metabolism* ; RNA, Messenger/genetics* ; RNA, Ribosomal ; RNA-Binding Proteins/metabolism* ; Transcription Factors/metabolism* ; Zygote/metabolism*

BACKGROUND: Insufficient cerebral perfusion is suggested to play a role in the development of Alzheimer disease (AD). However, there is a lack of direct evidence indicating whether hypoperfusion causes or aggravates AD pathology. We investigated the effect of chronic cerebral hypoperfusion on AD-related pathology in humans. METHODS: We enrolled a group of cognitively normal patients (median age: 64 years) with unilateral chronic cerebral hypoperfusion. Regions of interest with the most pronounced hypoperfusion changes were chosen in the hypoperfused region and were then mirrored in the contralateral hemisphere to create a control region with normal perfusion. 11C-Pittsburgh compound-positron emission tomography standard uptake ratios and brain atrophy indices were calculated from the computed tomography images of each patient. RESULTS: The median age of the 10 participants, consisting of 4 males and 6 females, was 64 years (47-76 years). We found that there were no differences in standard uptake ratios of the cortex (volume of interest [VOI]: P = 0.721, region of interest [ROI]: P = 0.241) and grey/white ratio (VOI: P = 0.333, ROI: P = 0.445) and brain atrophy indices (Bicaudate, Bifrontal, Evans, Cella, Cella media, and Ventricular index, P > 0.05) between the hypoperfused regions and contralateral normally perfused regions in patients with unilateral chronic cerebral hypoperfusion. CONCLUSION Our findings suggest that chronic hypoperfusion due to large vessel stenosis may not directly induce cerebral β-amyloid deposition and neurodegeneration in humans.
Aged ; Alzheimer Disease/pathology* ; Amyloid beta-Peptides/metabolism* ; Arteries ; Atrophy ; Brain/metabolism* ; Cerebral Cortex/metabolism* ; Cerebrovascular Circulation ; Constriction, Pathologic/pathology* ; Female ; Humans ; Magnetic Resonance Imaging/methods* ; Male ; Middle Aged ; Positron-Emission Tomography/methods*

BACKGROUND: Till date, the optimal treatment strategy for delivering adjuvant androgen deprivation therapy (ADT) in localized and locally advanced prostate cancer (PCa), as a lower stage in PCa progression compared with metastatic PCa, is still unclear. This study compares the efficacy of castration alone with complete androgen blockade (CAB) as adjuvant ADT in patients with localized and locally advanced PCa undergoing radical prostatectomy (RP). METHODS: Patients diagnosed with PCa, without lymph node or distant metastasis, who received RP in West China Hospital between January 2009 and April 2019, were enrolled in this study. We performed survival, multivariable Cox proportional hazard regression, and subgroup analyses. RESULTS: A total of 262 patients were enrolled, including 107 patients who received castration alone and 155 patients who received CAB. The survival analysis revealed that there was no significant difference between the two groups (hazard ratios [HR] = 1.07, 95% confidence intervals [95% CI] = 0.60-1.90, P = 0.8195). Moreover, the multivariable Cox model provided similarly negative results before and after adjustment for potential covariant. Similarly, there was no significant difference in the clinical recurrence between the two groups in both non-adjusted and adjusted models. Furthermore, our subgroup analysis showed that CAB achieved better biochemical recurrence (BCR) outcomes than medical castration alone as adjuvant ADT for locally advanced PCa (P for interaction = 0.0247, HR = 0.37, 95% CI = 0.14-1.00, P = 0.0497). CONCLUSION Combined androgen blockade achieved better BCR outcomes compared with medical castration alone as adjuvant ADT for locally advanced PCa without lymph node metastasis.
Androgen Antagonists/therapeutic use* ; Androgens ; Castration ; Humans ; Male ; Neoplasm Recurrence, Local/pathology* ; Prostatectomy/methods* ; Prostatic Neoplasms/surgery* ; Retrospective Studies

Objective:To investigate the risk factor analysis and model prediction of bleeding after endoscopic retrograde cholangiopancreatography in patients with malignant obstructive jaundice (MOJ).Methods:A retrospective analysis was performed on 302 patients with MOJ treated with ERCP who were treated in the No. 363 Hospital Affiliated to Southwest Medical University from January 2015 to June 2021. The general clinical data of the patients were collected, and the biochemical indicators of the pancreatic and bile ducts were detected. The patients were followed up after discharge, and the patients were divided into a bleeding group ( n=47) and a control group ( n=255) according to whether the follow-up patients were bleeding after ERCP. Compared the general and clinical data of the two groups of patients, including age, gender, platelet count, presence of bile duct stones, acute cholangitis, acute pancreatitis, number of stones, intraoperative bleeding, pancreatic cancer, cholangiocarcinoma, large stone diameter, stone incarceration, duodenal papillary diverticulum, and pre-surgical incision. The measurement data that obey the normal distribution were represented by the mean±standard deviation ( ± s), and the two independent sample t test was used for the comparison between groups; the data that do not conform to the normal distribution were represented by M ( Q1, Q3), and the comparison between groups was used Mann-Whitney U test. The comparison of enumeration data between groups adopted chi-square test. Logistic multivariate regression was used to analyze the independent risk factors of postoperative bleeding after ERCP, and a nomogram prediction model was established and verified according to the independent risk factors of postoperative bleeding. Results:The two groups of patients were compared in age, gender, platelet count, bile duct stones, acute cholangitis, acute pancreatitis, the number of stones, intraoperative bleeding and other aspects, the difference was not statistically significant ( P>0.05). The percentages of pancreatic cancer, cholangiocarcinoma, large stone diameter, stone incarceration, duodenal papillary diverticulum, and surgical pre-incision in the bleeding group were 12.77%, 17.02%, 19.15%, 51.06%, 59.57%, and 14.89%, respectively. , the percentages of the control group were 3.92%, 5.10%, 9.02%, 19.22%, 17.65%, and 5.88%, and the difference was statistically significant between the two groups ( P<0.05). Taking postoperative bleeding as the dependent variable, and using the indicators with statistical differences in univariate analysis as independent variables, multivariate Logistic regression analysis showed that the patient had pancreatic cancer ( OR=1.838, 95% CI: 1.524-4.613, P=0.041), cholangiocarcinoma ( OR=2.548, 95% CI: 1.870-5.116, P=0.015), stone incarceration ( OR=3.078, 95% CI: 2.374-6.012, P<0.001), duodenum Intestinal papillary diverticula ( OR=1.140, 95% CI: 1.045-1.628, P<0.001), surgical pre-incision ( OR=1.640, 95% CI: 1.321-1.928, P<0.001) were associated with postoperative bleeding in MOJ patients after ERCP independent risk factors. The predictive ability of duodenal papillary diverticulum was the highest; the predictive ability of stone incarceration and cholangiocarcinoma was the second, and there was no significant difference between them; the predictive ability of pancreatic cancer, stone diameter, and pre-incision on bleeding after ERCP in MOJ patients smaller. Pancreatic cancer, cholangiocarcinoma, large stone diameter, stone incarceration, duodenal papillary diverticulum, and pre-incision scores were 42, 63, 28, 65, 76, and 34 points respectively, and the total score was 308 points corresponding to the nomogram model. The predictive power of the nomogram was 61.6%, and overall, the nomogram had good predictive performance. Harrell concordance index analysis and ROC curve were used to evaluate the model discrimination, the C-index calculation result was 0.826 (95% CI: 0.771-0.847), the ROC curve AUC was 0.843 (95% CI: 0.801-0.884), and the ROC prediction The value and the calculation result of C-index are relatively close. The model discrimination is applied in this study and has a certain prediction effect. The nomogram model in the Calibration curve predicted the probability of postoperative bleeding after ERCP in MOJ patients with high consistency with the actual probability. Conclusion:ERCP is safe and feasible for most patients with MOJ, but for patients with pancreatic cancer, bile duct cancer, large stone diameter, stone incarceration, and duodenal papillary diverticulum, it should be performed with caution, and preoperative incision should be avoided, to reduce the risk of postoperative bleeding. In addition, the nomogram model has a strong predictive ability in predicting bleeding after ERCP in patients with MOJ, which is worthy of reference in clinical research.

Objective:To investigate the diagnostic value of 11C-Pittsburgh compound B (PIB) in patients with mild cognitive impairment (MCI) and Alzheimer′s disease (AD) and explore the factors that may affect the binding of 11C-PIB. Methods:From January 2017 to December 2019, the 11C-PIB uptake of 6 patients with normal cognitive (NC; 3 males, 3 females, age: (64.5±12.3) years), 11 patients with MCI (4 males, 7 females, age: (64.5±9.8) years) and 21 patients with AD (7 males, 14 females, age: (68.1±9.1) years) from Daping Hospital, Army Medical University were retrospectively analyzed. Regional 11C-PIB binding was assessed by using standardized uptake value ratio (SUVR) and visual reading of 11C-PIB scan. Clinical data, including age, gender, education level, cognitive impairment, neuropsychological scale score, vascular risk factors (VRF), apolipoprotein E (ApoE) gene, were collected and differences among groups were analyzed by using one-way analysis of variance, least significant difference t test or Fisher exact test. Factors that affected the 11C-PIB binding were analyzed by multiple linear regression. Results:SUVR of cerebral lobe among NC, MCI and AD groups were significantly different (range of mean SUVR: 1.16-1.26, 1.19-1.35 and 1.40-1.61; F values: 5.331-9.279, all P<0.05). For positive PIB patients, SUVR of posterior cingulate and precuneus were increased in MCI group compared with NC group (1.20±0.15 vs 1.50±0.12, 1.18±0.15 vs 1.59±0.13; F values: 6.389 and 10.668, t values: -2.33 and -3.10, both P<0.05), and there were no significant differences in all lobes between MCI and AD group ( t values: from -1.29 to -0.51, all P>0.05). Visual analysis showed that the positive rates of PIB in frontal lobe (85.7%(18/21)), posterior cingulate (85.7%(18/21)), precuneus (81.0%(17/21)), temporal lobe (81.0%(17/21)) and occipital lobe (47.6%(10/21)) in AD were higher than those in MCI (4/11, 4/11, 4/11, 3/11 and 1/11, respectively; all P<0.05). Multiple linear regression showed that the degree of cognitive impairment were independent risk factors for SUVR of all lobes ( b values: 0.377-0.536, all P<0.05). The ApoE ε4 gene was independent risk factor for SUVR of precuneus ( b=0.290, P<0.05). Conclusion:11C-PIB is helpful for clinical diagnosis of MCI and AD patients and the degree of cognitive impairment and ApoE ε4 gene may be independent risk factors for increasing 11C-PIB binding.

Objective:To retrospectively analyze the prevalence and genotype distribution of human papillomavirus (HPV) among women in mainland China from the introduction of cervical cancer vaccine to its marketing in China, so as to provide data for comparing HPV prevalence after the application and gradual promotion of HPV vaccine.Methods:Related articles published during 2006 to 2016 were retrieved from PubMed, China National Knowledge Infrastructure (CNKI) and Wanfang databases. Data about HPV infection in women receiving physical examination or routine cervical cancer screening and female outpatients were collected and analyzed.Result:A total of 270 articles were retrieved, in which the sampled women were aged from 13 to 90 years old. Seventy-two articles were about HPV infection in women screened for cervical cancer with a sample size of 580 308 people. The overall results showed that during the 11 years, the five most common high-risk HPV genotypes were HPV52, 16, 58, 68 and 18, and the common low-risk HPV genotypes were HPV81, 43 and 6. The distribution of HPV genotypes varied in different regions, but HPV16, 52 and 58 were always the predominant genotypes. Among the 270 collected articles, 200 analyzed HPV infection in female outpatients with a total of 675 035 cases. The results showed that the top five high-risk HPV genotypes with high prevalence were HPV16, 52, 58, 18 and 33, and the common low-risk types were HPV6, 11 and 81. The analysis of HPV infection rate in seven geographical regions indicated that, although the distribution of the commonly circulating high-risk HPV genotypes varied in different regions, HPV16, 52 and 58 remained the predominant genotypes.Conclusions:The present study showed that the prevalence and genotype distribution of HPV infection varied by region, but HPV16, 52 and 58 were always the most common high-risk genotypes and HPV6 was the predominant low-risk genotype in both women screened for cervical cancer and female outpatients. Besides that, the infections of other high-risk genotypes, such as HPV53 and 68, should also be of concern.