Prostate cancer is a prevalent malignant tumor of the male genitourinary system in China, with a persistently elevated incidence rate.Given the insidious onset, propensity for metastasis in advanced stages, and poor efficacy of traditional treatments, new hormone therapies have garnered increasing attention in recent years.A number of clinical studies have demonstrated that second-generation androgen receptor inhibitors (SGARIs), including enzalutamide, apalutamide, darolutamide, and rezvilutamide, can be beneficial in different stages of advanced prostate cancer.Furthermore, their early application has been shown to delay disease progression while maintaining a controlled safety profile.At present, SGARIs have increasingly become the primary therapeutic agents for advanced prostate cancer in various stages.This article reviews the clinical research progress of SGARIs in recent years, with the aim of offering valuable clinical reference for clinicians.

Xuefu zhuyu decoction is a classic formula for promoting blood circulation and resolving blood stasis， characterised by its remarkable ability to treat different diseases with the same approach. Qi stagnation and blood stasis， the primary syndrome for which this formula is indicated， has been found through modern medical research to be intrinsically linked to a wide range of pathophysiological processes， including microcirculatory disorders， abnormalities in hemorheology， inflammatory responses and endothelial dysfunction； which opens up vast scope for the innovative application of traditional formulas. In terms of pharmacological effect and mechanism， the formula exerts a synergistic regulatory effect across multiple key pathological pathways， including the regulation of coagulation function， the maintenance of vascular structure and function， anti-inflammatory and immunomodulatory actions， the mitigation of oxidative stress， and the modulation of programmed cell death （such as pyroptosis and ferroptosis）. This systematically demonstrates its scientific rationale， which is based on integrated regulation through multiple constituents， multiple targets and multiple pathways. In terms of clinical application， the formula has expanded from cardiovascular diseases to multiple disciplines， including gastroenterology， respiratory medicine， urology， neurology， endocrinology， gynaecology and andrology， with evidence-based medical evidence continuing to accumulate. Current research still faces bottlenecks such as a relatively low level of clinical evidence， insufficient systems biology analysis of the mechanisms underlying the compound’s formulation， and a weak correlation between quality control indicators and therapeutic efficacy. Future efforts should focus on conducting multicentre randomised controlled trials for conditions where the formula demonstrates particular efficacy， deepening research into the relationship between integrated pharmacology and spectrum-efficacy relationship， and promoting the precise application and formulation innovation of classical herbal formulas.

Xuefu zhuyu decoction is a classic formula for promoting blood circulation and resolving blood stasis， characterised by its remarkable ability to treat different diseases with the same approach. Qi stagnation and blood stasis， the primary syndrome for which this formula is indicated， has been found through modern medical research to be intrinsically linked to a wide range of pathophysiological processes， including microcirculatory disorders， abnormalities in hemorheology， inflammatory responses and endothelial dysfunction； which opens up vast scope for the innovative application of traditional formulas. In terms of pharmacological effect and mechanism， the formula exerts a synergistic regulatory effect across multiple key pathological pathways， including the regulation of coagulation function， the maintenance of vascular structure and function， anti-inflammatory and immunomodulatory actions， the mitigation of oxidative stress， and the modulation of programmed cell death （such as pyroptosis and ferroptosis）. This systematically demonstrates its scientific rationale， which is based on integrated regulation through multiple constituents， multiple targets and multiple pathways. In terms of clinical application， the formula has expanded from cardiovascular diseases to multiple disciplines， including gastroenterology， respiratory medicine， urology， neurology， endocrinology， gynaecology and andrology， with evidence-based medical evidence continuing to accumulate. Current research still faces bottlenecks such as a relatively low level of clinical evidence， insufficient systems biology analysis of the mechanisms underlying the compound’s formulation， and a weak correlation between quality control indicators and therapeutic efficacy. Future efforts should focus on conducting multicentre randomised controlled trials for conditions where the formula demonstrates particular efficacy， deepening research into the relationship between integrated pharmacology and spectrum-efficacy relationship， and promoting the precise application and formulation innovation of classical herbal formulas.

OBJECTIVE: To explore the effects of different endotracheal tube cuff pressure management modes on cuff sealing and the pressure exerted on the tracheal wall. METHODS: A prospective self-controlled study was conducted. Eleven patients undergoing endotracheal intubation and mechanical ventilation with an automatic airway management system (AGs) admitted to the Second Medical Centre of the Chinese People's Liberation Army General Hospital from October 1, 2020, to April 1, 2022, were enrolled as the study subjects. Within 24 hours after the establishment of artificial airway and mechanical ventilation, four cuff pressure management modes were randomly applied to each patient for 24 hours in sequence: automatic cuff pressure management mode [modeI: the safe range of cuff pressure was set at 20-35 cmH₂O (1 cmH₂O≈0.098 kPa), and the CO₂ pressure above the endotracheal tube cuff was automatically detected by AGs every 5 minutes to determine the cuff sealing status, and the cuff pressure was automatically adjusted], constant cuff pressure (25 cmH₂O) management mode (mode II: the cuff pressure was monitored by AGs through a pressure sensor, and the cuff pressure was maintained at 25 cmH₂O via a pressure pump), constant cuff pressure (30 cmH₂O) management mode (mode III: the cuff pressure was monitored by AGs through a pressure sensor, and the cuff pressure was maintained at 30 cmH₂O via a pressure pump), and manual cuff pressure management mode (mode IV: the cuff pressure was manually measured by nurses every 6-8 hours using a cuff pressure gauge to keep the cuff pressure at 25-30 cmH₂O after inflation). The CO₂ pressure above the endotracheal tube cuff (at 60-minute intervals) and the cuff pressure changes (at 50-ms intervals) were recorded to compare the differences in number of cuff leaks [no leak was defined as CO₂ pressure = 0, small leak as 0 < CO₂ pressure < 2 mmHg (1 mmHg≈0.133 kPa), and large leak as CO₂ pressure ≥ 2 mmHg] and cuff pressure among modesI-IV. RESULTS: A total of 24 CO₂ pressure measurements were taken per patient across the four modes, resulting in a total of 264 detections for each mode. Regarding the cuff leak, the total number of leak and large leak in modeIwas significantly lower than that in modes II-IV [total leak: 30 cases (11.36%) vs. 81 cases (30.68%), 70 cases (26.52%), 103 cases (39.02%); large leak: 15 cases (5.68%) vs. 50 cases (18.94%), 48 cases (18.18%), 66 cases (25.00%), all P < 0.05]. There was no significant difference in the number of cuff leak between modes II and III, and mode IV had the most severe cuff leak. In terms of cuff pressure, since mode IV required blocking the cuff tube from the AGs tube and the AGs cuff pressure management module did not actually work, real-time monitoring of cuff pressure was not possible. Therefore, cuff pressure changes were only analyzed in modes I-III. Each of the 11 patients underwent 24-hour cuff pressure monitoring under modes I-III, with 19 008 000 monitoring times for each mode. The cuff pressure in mode I was between that in modes II and III [cmH₂O: 27.09 (26.10, 28.14) vs. 26.60 (25.92, 27.47), 31.01 (30.33, 31.88), both P < 0.01]. Moreover, the number of extreme values of cuff pressure > 50 cmH₂O in mode I was significantly lower than that in modes II and III [19 900 cases (0.105%) vs. 22 297 cases (0.117%), 27 618 cases (0.145%), both P < 0.05]. CONCLUSION Dynamically monitoring the CO₂ pressure above the cuff to guide the adjustment of endotracheal tube cuff pressure can achieve better cuff sealing with a relatively lower cuff pressure load.
Humans ; Intubation, Intratracheal/instrumentation* ; Pressure ; Prospective Studies ; Respiration, Artificial ; Male ; Airway Management/methods* ; Female ; Middle Aged

OBJECTIVE To investigate the independent risk factors for carbapenem-resistant Klebsiella pneumoniae （CRKP） infection， develop a nomogram prediction model and validate it. METHODS Clinical data of hospitalized patients infected with CRKP between April 2020 and May 2023 at Kunming First People’s Hospital were retrospectively collected and matched 1∶1 with patients infected with carbapenem-susceptible Klebsiella pneumoniae （CSKP） during the same period as the modeling group. Using the same criteria， data from patients hospitalized and infected with CRKP and matched CSKP between June 2023 and June 2024 were collected as the validation group. Univariate analysis， LASSO regression and multivariate Logistic regression were conducted to identify independent risk factors for CRKP infection and to develop a nomogram prediction model. Internal validation of the model was performed using Bootstrap resampling， and external validation was carried out using the data of validation group. The predictive performance of the model was evaluated using receiver operating characteristic （ROC） curves and calibration plots. RESULTS A total of 530 patients were enrolled， with 372 in the modeling group and 158 in the validation group. Cerebrovascular disease， indwelling gastric tube， mechanical ventilation， exposure to carbapenem antibiotics， and exposure to β-lactamase inhibitor compound agents were identified as independent risk factors for CRKP infection （P＜0.05）. The nomogram predicting CRKP infection risk achieved an area under ROC of 0.729 and 0.803 in internal and external validations， respectively. Calibration curves indicated a high degree of consistency between predicted and observed probabilities. CONCLUSIONS Cerebrovascular disease， indwelling gastric tube， mechanical ventilation， exposure to carbapenem antibiotics， and exposure to β-lactamase inhibitor compound agent are independent risk factors for CRKP infection. The developed nomogram model for predicting CRKP infection risk demonstrates good predictive performance and can aid in the early identification of patients at high risk for CRKP infection.

OBJECTIVE: To explore the effectiveness of arthroscopic release of elbow joint assisted by medial small incision ulnar nerve release in the treatment of non-traumatic elbow stiffness. METHODS: The clinical data of 15 patients with non-traumatic elbow stiffness treated with arthroscopic release of elbow joint assisted by medial small incision ulnar nerve release between April 2019 and September 2023 were retrospectively analyzed. There were 6 males and 9 females with an average age of 46 years ranging from 34 to 56 years. The causes included rheumatoid arthritis in 3 cases, gouty arthritis in 2 cases, loose bodies in 3 cases, and elbow osteoarthritis in 7 cases. There were 4 cases with ulnar neuritis and 3 cases with synovial osteochondromatosis. The duration of elbow stiffness ranged from 6 to 18 months, with an average of 10 months. The operation time and intraoperative blood loss were recorded. The effectiveness was evaluated by visual analogue scale (VAS) score, range of elbow motion (maximum flexion, maximum extension, and total flexion and extension), Mayo score, and Hospital for Special Surgery (HSS) elbow score. RESULTS: The operation time was 60-90 minutes, with an average of 65 minutes, and the intraoperative blood loss was 40-100 mL, with an average of 62 mL. All patients were followed up 13-18 months, with an average of 14 months. There was no complication such as vascular and nerve injury, poor wound healing, collateral ligament injury, elbow joint space narrowing, osteophyte proliferation, or loose body formation around the joint. At last follow-up, the elbow range of motion (maximum flexion, maximum extension, and total flexion and extension), VAS score, and Mayo score significantly improved when compared with those before operation ( P<0.05). The HSS elbow score was 85-95, with an average of 92; 12 cases were excellent, 3 cases were good, and the excellent and good rate was 100%. CONCLUSION Arthroscopic release of elbow joint assisted by medial small incision ulnar nerve release is an effective way to treat non-traumatic elbow stiffness, which has the advantages of small trauma, short operation time, and good effectiveness. It can carry out early elbow rehabilitation training and significantly improve elbow function.
Humans ; Male ; Female ; Arthroscopy/methods* ; Adult ; Middle Aged ; Elbow Joint/physiopathology* ; Retrospective Studies ; Range of Motion, Articular ; Treatment Outcome ; Ulnar Nerve/surgery* ; Operative Time

Objective Zinc finger protein 335 (Zfp335) plays a crucial role in the early development of thymic T cells and the differentiation of peripheral T cell subpopulations. The objective of this study is to investigate the role and underlying mechanisms of Zfp335 in the regulation of regulatory T cell (Treg) within tumor immunity. Methods The Zfp335 gene was specifically knocked out in Treg using tamoxifen (Zfp335^fl/fl FOXP3^creERT2), and the MC38 tumor model was established. On the 7th day after tumor inoculation, tumor size was observed and measured. Tumor size was monitored and recorded daily starting from day 7 post-inoculation. On day 12, tumors were harvested, and the proportions of CD4⁺ T cells, CD8⁺ T cells, and Treg were analyzed by flow cytometry. Additionally, the mitochondrial function of effector regulatory T cell (eTreg) was assessed. Results From day 10 post-tumor inoculation, tumor volume in the Zfp335^CKO group was significantly reduced compared to that of the wild-type (WT) group. Furthermore, the infiltration of CD4⁺ and CD8⁺ T cells, along with their respective effector cells, was significantly higher in the Zfp335^CKO group than in the WT group. The proportions of CD4⁺ and CD8⁺ T cells producing interferon-gamma (IFN-γ) and tumor necrosis factor-alpha (TNF-α) were also significantly increased in the Zfp335^CKO group compared to that of the WT group. In addition, the percentage of CD8⁺ T cells secreting granzyme B (GzmB) was significantly higher in the Zfp335^CKO group than that in the WT group. In contrast, the proportion of Treg and inducible T cell co-stimulator (ICOS)⁺ Treg in the Zfp335^CKO group was significantly lower than that in the WT group. Finally, the expression level of Mitotracker Deep Red in eTreg from the Zfp335^CKO group was significantly reduced compared to that in the WT group. Conclusion During tumorigenesis, the specific deletion of Zfp335 impairs Treg activation, which is related to decreased mitochondrial function in eTreg. In Zfp335^CKO mice. Tumors exhibit increased infiltration of effector T cells, accompanied by elevated levels of cytotoxic cytokines, ultimately enhancing resistance to tumor progression.
Animals ; T-Lymphocytes, Regulatory/metabolism* ; Mice ; CD8-Positive T-Lymphocytes/immunology* ; Neoplasms/genetics* ; Cell Line, Tumor ; Mice, Inbred C57BL ; Mice, Knockout ; DNA-Binding Proteins/genetics* ; Female

Objective: To investigate the characteristics of the breakthrough cases of mumps in Ningbo City, Zhejiang Province from 2018 to 2023, so as to provide insights into improving prevention and control measures for mumps. Methods: Data of mumps cases and mumps containing vaccine (MuCV) vaccination in Ningbo City from 2018 to 2023 were collected through the Infectious Disease Reporting Information System of Chinese Disease Prevention and Control Information System and Zhejiang Immunization Planning Information System. The population distribution characteristics and MuCV immunization history of mumps breakthrough cases were described. The impacts of the final immunization age and immunization interval on the age of onset were analyzed. Results: A total of 6 643 mumps cases were reported in Ningbo City from 2018 to 2023, with an average incidence rate of 11.72/105. There were 5 142 breakthrough cases (77.40%), including 3 173 males (61.71%) and 1 969 females (38.29%). The median age of onset was 6.00 (interquartile range, 4.00) years. There were 2 487 cases in preschool children (48.37%) and 2 232 cases in students (43.41%). There were 4 736 one-dose breakthrough cases (92.10%) and 406 two-dose breakthrough cases (7.90%). The proportion of two-dose breakthrough cases among all mumps cases increased from 1.00% in 2018 to 25.32% in 2023. Among individuals born after December 2018, the median age of onset of two-dose breakthrough cases was 3.00 (interquartile range, 1.00) years, which was older than that of one-dose breakthrough cases at 1.00 (interquartile range, 2.00) year (P<0.05). The ages of onset of mumps breakthrough cases differed significantly with varying final immunization ages and immunization intervals (both P<0.05). Conclusions The breakthrough cases of mumps in Ningbo City from 2018 to 2023 were mainly males, preschool children and students. The proportion of two-dose breakthrough cases increased, and the age of onset delayed.

Prostate cancer(PCa)is the most common malignant tumor of the male urinary and reproductive systems,with its incidence and mortality rates steadily increasing worldwide.Enhancing early detection of PCa and refining surgical treatment methods are crucial for improving cure rates,extending survival,and enhancing quality of life.Prostate biopsy remains the gold standard for diagnosing PCa,utilizing approaches such as transrectal,transperineal,and multi-imaging guided fusion-targeted techniques.Surgical intervention is a key treatment modality for PCa,with radical prostatectomy(RP)serving as the gold standard for managing localized disease.This paper reviews recent advancements in surgical techniques for prostate cancer,aiming to provide clinical practitioners with updated guidance.

Objective To understand the membrane protein molecular epidemiology of carbapenem-resistant Pseudomonas aeruginosa (CRPA) in the region,and provide some evidence for rational drug use or application of efflux pump inhibitors. Methods Collected Pseudomonas aeruginosa isolated from four hospitals in the region from October 2022 to August 2023,and used SYBR-PCR method to quantitatively detect the relative mRNA expression (RE) levels of 10 membrane protein coding genes,including mexA,B,C,D,E,F,X,Y,and oprD,M. Then categorized the strains into five groups based on ceftazidime,cefepime,imipenem,and meropenem resistance phenotype combination,including the compassionate group (Group Ⅰ),Group Ⅱ with full resistance,IPM,MEM resistant,CAZ and CFP sensitive groups (Group Ⅲ),IPM resistance,MEM non-resistance (sensitive or intermediate) group (Group Ⅳ),IPM,MEM resistance,CAZ and CFP non-resistance groups (Group V).The median RE of each membrane protein-coding gene was analyzed. Results A total of 108 strains of Pseudomonas aeruginosa were collected,with 24 strains in Group Ⅰ as controls and 84 strains in the carbapenem resistant group,including 32 strains in Group Ⅱ,22 strains in Group Ⅲ,13 strains in Group Ⅳ,and 17 strains in Group Ⅴ. The expression of mexD,mexE,mexF,mexX and mexY in the drug-resistant group was higher than that in the control group,and the differences were statistically significant (U=409.5～661.0,all P<0.05). There was no statistically significant difference in mexA,mexB,mexC,oprD and oprM with the control group (U=767.0～1004.5,all P>0.05). There was no significant difference in the expression of RE genes encoding various membrane proteins among strains from different hospitals (H=0.914～7.407,all P>0.05). Among the four different phenotypes,there was no statistically significant difference in the irregular distribution of mexA and oprM RE between each group and the control group (UmexA=95.0～264.0,UoprM=143.0～331.0). The mexC RE in each group was lower than that in the control group,but the differences were not statistically significant (U=134.0～344.5,all P>0.05). MeixE and meixY RE were both higher than the control group,and the differences were statistically significant (UmexE=48.0～230.0,UmexY=83.0～184.0). MeixB was lower than the control group in group Ⅳ (U=72.0),and the differences were statistically significant (all P<0.05). MeixD and meixF showed consistent expression,with higher expression in groups Ⅲ,Ⅳ and Ⅴ compared to the control group (UmeixD=34.0～102.0,UmeixF=65.0～113.0). MeixX was expressed higher in groups Ⅱ,Ⅳ and Ⅴ compared to the control group (U=164.0,58.0,111.0),while oprD was only expressed lower in group Ⅲ than in the control group (U=140.0),with statistically significant differences (all P<0.05). Although the expression of oprD in groups Ⅱ,Ⅳ and Ⅴ was lower than that in the control group,the differences were not statistically significant (U=381.0,102.0,144.0,all P>0.05). Conclusion ExCD,mexEF and mexXY are the main membrane protein combinations of CRPA efflux pumps in Kunming area. Upregulation of mexD,E,F,X,and Y membrane protein expression enhanced efflux. The correlation between mexAB oprM efflux pump and carbapenem resistance in CRPA in this area was low. The low expression of oprD played a role in the efflux mechanism in strains that do not produce β-lactase,but there was no significant difference in low expression in enzyme producing strains.