OBJECTIVE: To investigate the safety and prognostic factors influencing the treatment of upper urinary tract urothelial carcinoma (UTUC) combined with bladder cancer (BCa) by laparoscopic simultaneous radical cystectomy and nephroureterectomy (RCNU). METHODS: The clinical data of patients admitted to Peking University Third Hospital for laparoscopic RCNU surgery from January 2009 to September 2023 were analyzed retrospectively. Based on the same gender, age (±5 years), history of uroepithelial tumors, underlying diseases, T-stage, N-stage, M-stage, American Society of Anesthesiologists (ASA) score, Charlson comorbidity index, and body mass index (BMI) (±5), 34 patients with RCNU were matched 1 ∶1 with patients with bladder cancer who underwent laparoscopic radical cystectomy (RC) alone. Kaplan-Meier survival analysis was used to calculate patient survival, and Cox proportional regression risk model was used to analyze clinical factors affecting prognosis. RESULTS: Of the 68 patients enrolled, the follow-up rate was 100% with a median follow-up time of 27.0 (11.7, 60.2) months. Comparison of intraoperative conditions (including operation time, estimated intraoperative bleeding, intra-operative blood transfusion, etc.) between the two groups of patients showed no significant difference (P>0.05). Comparison of preoperative creatinine and postoperative creatinine between the two groups of patients showed significant differences (P < 0.05). The perioperative Clavien grade Ⅲ-Ⅳ complication rates were 2.9% (1/34) in the RC group and 5.9% (2/34) in the RCNU group. There was no significant difference in terms of perioperative complications between the two groups. Overall survival was significantly lower in the patients receiving RCNU compared with the matched group receiving RC alone (P < 0.05). Cox regression analysis suggested that two factors, high N stage and high postoperative creatinine, were independent risk factors affecting the prognosis of patients in the 2 groups (P < 0.05). CONCLUSION The overall survival prognosis of patients undergoing RCNU surgery was worse compared with laparoscopic RC surgery alone during the same period. There was no clinically significant difference between the two groups in terms of operation time, intraoperative bleeding, and perioperative complications, and there were clinically significant differences in preoperative renal function and post-operative renal function.
Humans ; Laparoscopy/methods* ; Nephroureterectomy/methods* ; Cystectomy/methods* ; Prognosis ; Male ; Retrospective Studies ; Female ; Urinary Bladder Neoplasms/mortality* ; Middle Aged ; Aged

Myocardial fibrosis is a serious cause of heart failure and even sudden cardiac death. However, the mechanisms underlying myocardial ischemia-induced cardiac fibrosis remain unclear. Here, we identified that the expression of sterile alpha and TIR motif containing 1 (SARM1), was increased significantly in the ischemic cardiomyopathy patients, dilated cardiomyopathy patients (GSE116250) and fibrotic heart tissues of mice. Additionally, inhibition or knockdown of SARM1 can improve myocardial fibrosis and cardiac function of myocardial infarction (MI) mice. Moreover, SARM1 fibroblasts-specific knock-in mice had increased deposition of extracellular matrix and impaired cardiac function. Mechanically, elevated expression of SARM1 promotes the deposition of extracellular matrix by directly modulating P4HA1. Notably, by using the Click-iT reaction, we identified that the increased expression of ZDHHC17 promotes the palmitoylation levels of SARM1, thereby accelerating the fibrosis process. Based on the fibrosis-promoting effect of SARM1, we screened several drugs with anti-myocardial fibrosis activity. In conclusion, we have unveiled that palmitoylated SARM1 targeting P4HA1 promotes collagen deposition and myocardial fibrosis. Inhibition of SARM1 is a potential strategy for the treatment of myocardial fibrosis. The sites where SARM1 interacts with P4HA1 and the palmitoylation modification sites of SARM1 may be the active targets for anti-fibrosis drugs.

This paper summarized Professor LI Yueqing's clinical experience in treating prostate cancer by stages from the perspective of deficiency and stasis. It is believed that the onset of prostate cancer is due to kidney deficiency， while blood stasis is the core pathogenesis， and dampness-heat， phlegm-turbid， and cancer toxins are the key pathological factors in the progression of the disease. The pathogenesis in the early stage of the disease is kidney qi depletion and dampness， heat and phlegm coagulation； in the middle stage， it is spleen and kidney depletion， phlegm coagulation and blood stasis； and in the late stage， the pathogenesis changes into yin deficiency and essence depletion， and stasis-turbid toxin obstruction. For treatment， the basic principle is to supplement and boost kidney qi， enrich and nourish the kidney yin. The main treatment methods are draining dampness， dissolving phlegm， dispelling stasis， clearing heat and resolving toxins， and the method of invigorating blood and dispelling stasis runs through the whole course of treatment. In the early stage， radical treatment is mainly used， and Longshe Yangquan Decoction （龙蛇羊泉汤） with modifications is supplemented to clear and drain dampness and heat. In the middle stage， androgen deprivation therapy is the basic treatment， and Bushen Tongqiao Decoction （补肾通窍汤） with modifications is used in combination to nourish the spleen and kidney， dissolve phlegm and dispel stasis. In the late stage， Dabuyin Pills and Liuwei Dihuang Pills （大补阴丸合六味地黄丸） with modifications is mainly used to enrich yin and supplement essence， resolve toxins and dissolve stasis， and prevent cancer recurrence.

Generative artificial intelligence (GAI) refers to AI technology capable of generating new content such as text, images, or audio from training data. GAI tools not only demonstrate rapid and efficient potential in literature screening, data extraction, and literature appraisal in systematic reviews, but can also be used for guideline evaluation and dissemination, enhancing the readability and promotion efficiency of guidelines. However, the accuracy of content generated by GAI tools, the rationality of cited evidence, the level of evidence, and the reliability of data still need verification. Additionally, data privacy protection and ethical issues are challenges that need to be addressed. This article aims to overview the current status of GAI tools in the formulation, evaluation, dissemination, and implementation of guidelines, explore the feasibility and new models of GAI tools in the field of guidelines, and improve the efficiency and quality of guideline formulation to better serve guideline developers and users.

Osteoporotic proximal humeral fracture (OPHF) is one of the common osteoporotic fractures in the aged, with an incidence only lower than vertebral compression fracture, hip fracture, and distal radius fracture. OPHF, secondary to osteoporosis and characterized by poor bone quality, comminuted fracture pattern, slow healing, and severely impaired shoulder joint function, poses a big challenge to the current clinical diagnosis and treatment. In the field of diagnosis, treatment, and rehabilitation of OPHF, traditional Chinese and Western medicine have accumulated rich experience and evidence from evidence-based medicine and achieved favorable outcomes. However, there is still a lack of guidance from a relevant consensus as to how to integrate the advantages of the two medical systems and achieve the integrated diagnosis and treatment. To promote the diagnosis and treatment of OPHF with integrated traditional Chinese and Western medicine, relevant experts from Orthopedic Expert Committee of Geriatric Branch of Chinese Association of Gerontology and Geriatrics, Youth Osteoporosis Group of Orthopedic Branch of Chinese Medical Association, Osteoporosis Group of Orthopedic Surgeon Branch of Chinese Medical Doctor Association, and Osteoporosis Committee of Shanghai Association of Integrated Traditional Chinese and Western Medicine have been organized to formulate Expert consensus on the diagnosis and treatment of osteoporotic proximal humeral fracture with integrated traditional Chinese and Western medicine ( version 2024) by searching related literatures and based on the evidences from evidence-based medicine. This consensus consists of 13 recommendations about the diagnosis, treatment and rehabilitation of OPHF with integrated traditional Chinese medicine and Western medicine, aimed at standardizing, systematizing, and personalizing the diagnosis and treatment of OPHF with integrated traditional Chinse and Western medicine to improve the patients ′ function.

Objective:To investigate the prognostic factors for all-cause mortality in patients with muscle-invasive bladder cancer(MIBC)with intermediate-to-high-risk primary prostate cancer.Methods:From January 2012 to October 2023,the clinical data of the patients with MIBC with intermediate-to-high-risk primary prostate cancer in Peking University Third Hospital were retrospectively analyzed.All the patients were monitored and the occurrence of all-cause death was documented as the outcome event in the prognostic study.Univariate and multivariate Cox proportional risk regression analysis models were implemented to search for independent influences on the prognosis of patients.For significant influencing factors(pathological T stage,M stage and perineural invasion of bladder cancer),survival curves were plotted before and after multifactorial Cox regression adjusting for confounding factors.Results:A total of 32 patients were included in this study.The mean age was(72.5±6.6)years;the median preoperative total prostate specific antigen(tPSA)was 6.68(2.47,6.84)μg/L;the mean preoperative creatinine was(95±36)μmol/L,and the median survival time was 65 months.The majority of the patients(87.5％)had high-grade bladder cancer,53.1％had lymphatic invasion,and 31.3％had perineural invasion.Prostate involvement was observed in 25.0％of the cases,and the positive rate of soft-tissue surgical margin was 37.5％.Multivariate Cox analysis revealed that preoperative creatinine level(HR=1.02,95％CI:1.01-1.04),pathological stage of bladder cancer T3(HR=11.58,95％CI:1.38-97.36)and T4(HR=19.53,95％CI:4.26-89.52)metastasis of bladder cancer(HR=9.44,95％CI:1.26-70.49)and perineural invasion of bladder cancer(HR=6.26,95％CI:1.39-28.27)were independent prognostic factors(P＜0.05).Survival curves with Log-rank test after adjusting for confounding factors demonstrated that bladder cancer pathology T3,T4,M1,and perineural invasion were unfavorable factors affecting the patients'survival prognosis(P＜0.05).Conclusion:Patients with MIBC with intermediate-to-high risk primary prostate cancer generally portends a poor prognosis.High preoperative serum creatinine,T3 or T4 pathological stage of bladder cancer,metastasis of bladder cancer and bladder cancer perineural invasion are poor prognostic factors for patients with MIBC with intermediate-to-high risk primary prostate cancer.

Objective To determine the effects of treadmill training on the structure of hippocampal myelin and cognitive function in rats exposed to acute plateau hypoxia.Methods With 30 SPF-grade female SD rats (aged 6-8 weeks,weighing 200-220 g),6 of them were used for observation of myelin structure after injury,and the remaining 24 rats were randomly divided into control group,hypobaric hypoxia group and treadmill training group (n=8).The rats in above experimental groups were placed in a low-pressure oxygen chamber at an altitude of 6000 m for 7 consecutive days,and the rats of the control group were placed in the confined chamber for the same period without hypoxia.Then,the rats of the treadmill training group received a 4-week treadmill training scheme since the day after hypoxia.Finally,all the rats were tested for cognitive function with open field test (OFT)and Morris water maze (MWM).Transmission electron microscopy (TEM) was used to observe the changes of demyelination in the hippocampus. The expression of oligodendrocyte transcription factor 2 (Olig2)and myelin basic protein (MBP )in the hippocampal CA1 and CA3 regions was measured by immunofluorescence staining and Western blotting.Results Behavioral tests showed that the number into the central area,total distance,distance ratio in OFT and the number of platform crossings and distance to the target area in MWM were reduced in the hypobaric hypoxia group than the control group (P<0.05 ),while these indexes were increased in the treadmill training group than in the hypobaric hypoxia group (P<0.05).Immunofluorescence staining indicated that the number of Olig2 positive cells per unit area and the mean fluorescence intensity of MBP in the CA1 and CA3 regions were significantly lessen in the hypobaric hypoxia group than the control group (P<0.05 ),while these indicators were higher in the treadmill training group than the hypobaric hypoxia group (P<0.05 ).Western blotting displayed that the expression levels of Olig2 and MBP in the hippocampus were obviously lower in the hypobaric hypoxia group than the control group (P<0.01 ),while the levels were increased in the treadmill training group than the hypobaric hypoxia group (P<0.01 ).Conclusion Treadmill training promotes the number of the oligodendrocyte spectrum cells in CA1 and CA3 regions,enhances the expression of myelin-related proteins and improves myelin repair in hippocampus of hypobaric hypoxia rats,and thereby ameliorates hypoxia-induced anxiety-like behaviors and memory dysfunction.

Ghrelin is a hormone produced by the stomach that regulates energy metabolism after acting on the central nervous system.Cocaine amphetamine-regulated transcriptional peptide(CART)neurons participate in the regulation of feeding behavior and energy balance.It is known that CART neurons are influenced by hormones to regulate energy homeostasis,but whether ghre-lin exerts its pro-appetite function by influencing CART neurons is unknown.Therefore,this study focuses on the role of VMHCART neurons in the regulation of feeding and relative body weight by ghrelin.Firstly,the whole brain expression of CART was determined by immunofluorescence.Then the effect of intraperitoneal injection of ghrelin on the expression of DMHCART neurons was evalua-ted.Finally,the ghrelin was delivered to DMH and the changes of food intake and relative body weight of mice were measured.CART immunoreactive neurons were detected in medial preoptic nucleus(MPA),arcuate nucleus(ARC),dorsomedial hypothalamic nucleus(DMH),thalamic pa-raventricular nucleus(PVT)and raphe nucleus(ROb).Compared with the control group,periph-eral injection of ghrelin significantly increased the expression of DMHC ART immunoreactive neurons(P=0.037 3).DMH long-term injection of ghrelin resulted in an increase in body weight(P=0.004 0)and feed intake(P=0.023 1).The results provide anatomical evidence for the whole brain distribution of CART,which proves that ghrelin affects feed intake and body weight of mice through CART neurons in DMH,suggesting that specific neuron types and regional specificity are involved in ghrelin regulation of feed intake and energy homeostasis.

Vesicular glutamate transporter 2(VGlut2)is expressed in the PVN of the hypothalamic paraventricular nucleus(PVNVG1ut2)as an excitatory neurotransmitter,which regulates food intake and energy metabolism and plays an important role in maintaining homeostasis.However,it is not clear that the upstream and downstream projection network of PVNVGut2 neurons hinders the anal-ysis of glutamatergic neuron circuit function.Anterograde and retrograde tracer viruses were injec-ted into the PVN of VGlut2 mice by stereotactic brain injection technique to find the input and output nuclei of PVNVGlut2 neurons.Anterograde tracing results showed that PVNVGlut2 neurons pro-jected to the downstream medial amygdala(MeAD)and arcuate nucleus(ARC).Retrograde trac-ing results showed that PVNVGlut2 received input from the prefrontal nucleus(Pr),the reticular tegmental nucleus(RtTg),and the hypoglossal nucleus(12N).In addition,VGlut2 was found to be co-expressed with neuronal nitric oxide synthase(nNOS)neurons in the PVN.The anatomical net-work of PVNVG1ut2 neurons was analyzed by virus tracking tool,which laid the anatomical founda-tion for further study on the functional regulation of PVNVGlut2.