Prostate cancer(PCa)is currently the second most common malignancy in men worldwide,and its incidence rate is on the rise.Most cases of PCa are treated by radical prostatectomy,but with the development of medical imaging and innovation in therapeutic theories and technology,focal therapy has shown better application prospects in the treatment of PCa.Compared with radi-cal prostatectomy,focal therapy yields satisfactory results in terms of effectiveness and reduction of complications in addition to avoid-ance of overtreatment and treatment-related financial burden.This article reviews the strategies of focal therapy for PCa,including cryo-ablation,high-intensity focused ultrasound,irreversible electroporation,and photodynamic therapy,with an analysis of the clinical tri-als in recent years.

Objective:To estimate tissue/organ doses and effective dose to operators in the overexposure incident during an interventional procedure using Monte Carlo method.Methods:The phantoms were constructed for both the operators and the patient based on the adult mesh-type reference computational phantoms (MRCPs) recommended by the International Commission on Radiological Protection (ICRP) Publication 145 and phantom deformation technology. Models of exposure scenario were constructed based on the on-site equipment and the irradiation conditions. The Monte Carlod simulation method was used to evaluate the absorbed dose to critical tissues and organs, such as the operator′s eye lens and thyroid, as well as the effective dose.Results:In the particular exposure conditions, the maximum absorbed doses in the primary organs of the two operators were in the left eye lens, with doses of 1.216 and 0.223 mGy, respectively. The thyroid absorbed doses were 0.074 and 0.019 mGy, while the effective doses to the two operators were 0.088 and 0.021 mSv, respectively. The reduction rates of effective dose for the two operators when wearing lead aprons and lead thyroid collars were 67.16% and 78.79%, respectively.Conclusions:The combination of Monte Carlo method and MRCPs can be used to restore a specific irradiation scenario to a high degree and to estimate the physical dose of to the irradiated persons.

Purpose::Vibrio vulnificus ( V. Vulnificus) infection is characterized by rapid onset, aggressive progression, and challenging treatment. Bacterial resistance poses a significant challenge for clinical anti-infection treatment and is thus the subject of research. Enhancing host infection tolerance represents a novel infection prevention strategy to improve patient survival. Our team initially identified cytochrome P4501A1 (CYP1A1) as an important target owing to its negative modulation of the body's infection tolerance. This study explored the superior effects of the CYP1A1 inhibitor bergamottin compared to antibiotic combination therapy on the survival of mice infected with multidrug-resistant V. Vulnificus and the protection of their vital organs. Methods::An increasing concentration gradient method was used to induce multidrug-resistant V. Vulnificus development. We established a lethal infection model in C57BL/6J male mice and evaluated the effect of bergamottin on mouse survival. A mild infection model was established in C57BL/6J male mice, and the serum levels of creatinine, urea nitrogen, aspartate aminotransferase, and alanine aminotransferase were determined using enzyme-linked immunosorbent assay to evaluate the effect of bergamottin on liver and kidney function. The morphological changes induced in the presence of bergamottin in mouse organs were evaluated by hematoxylin and eosin staining of liver and kidney tissues. The bacterial growth curve and organ load determination were used to evaluate whether bergamottin has a direct antibacterial effect on multidrug-resistant V. Vulnificus. Quantification of inflammatory factors in serum by enzyme-linked immunosorbent assay and the expression levels of inflammatory factors in liver and kidney tissues by real-time quantitative polymerase chain reaction were performed to evaluate the effect of bergamottin on inflammatory factor levels. Western blot analysis of IκBα, phosphorylated IκBα, p65, and phosphorylated p65 protein expression in liver and kidney tissues and in human hepatocellular carcinomas-2 and human kidney-2 cell lines was used to evaluate the effect of bergamottin on the nuclear factor kappa-B signaling pathway. One-way ANOVA and Kaplan-Meier analysis were used for statistical analysis. Results::In mice infected with multidrug-resistant V. Vulnificus, bergamottin prolonged survival ( p = 0.014), reduced the serum creatinine ( p = 0.002), urea nitrogen ( p = 0.030), aspartate aminotransferase ( p = 0.029), and alanine aminotransferase ( p = 0.003) levels, and protected the cellular morphology of liver and kidney tissues. Bergamottin inhibited interleukin (IL)-1β, IL-6, and tumor necrosis factor (TNF)-α expression in serum (IL-1β: p = 0.010, IL-6: p = 0.029, TNF-α: p = 0.025) and inhibited the protein expression of the inflammatory factors IL-1β, IL-6, TNF-α in liver (IL-1β: p = 0.010, IL-6: p = 0.011, TNF-α: p = 0.037) and kidney (IL-1β: p = 0.016, IL-6: p = 0.011, TNF-α: p = 0.008) tissues. Bergamottin did not affect the proliferation of multidrug-resistant V. Vulnificus or the bacterial load in the mouse peritoneal lavage fluid ( p = 0.225), liver ( p = 0.186), or kidney ( p = 0.637). Conclusion::Bergamottin enhances the tolerance of mice to multidrug-resistant V. Vulnificus infection. This study can serve as a reference and guide the development of novel clinical treatment strategies for V. Vulnificus.

Management and treatment of terminal metastatic castration-resistant prostate cancer (mCRPC) remains heavily debated. We sought to investigate the efficacy of programmed cell death 1 (PD-1) inhibitor plus anlotinib as a potential solution for terminal mCRPC and further evaluate the association of genomic characteristics with efficacy outcomes. We conducted a retrospective real-world study of 25 mCRPC patients who received PD-1 inhibitor plus anlotinib after the progression to standard treatments. The clinical information was extracted from the electronic medical records and 22 patients had targeted circulating tumor DNA (ctDNA) next-generation sequencing. Statistical analysis showed that 6 (24.0%) patients experienced prostate-specific antigen (PSA) response and 11 (44.0%) patients experienced PSA reduction. The relationship between ctDNA findings and outcomes was also analyzed. DNA-damage repair (DDR) pathways and homologous recombination repair (HRR) pathway defects indicated a comparatively longer PSA-progression-free survival (PSA-PFS; 2.5 months vs 1.2 months, P = 0.027; 3.3 months vs 1.2 months, P = 0.017; respectively). This study introduces the PD-1 inhibitor plus anlotinib as a late-line therapeutic strategy for terminal mCRPC. PD-1 inhibitor plus anlotinib may be a new treatment choice for terminal mCRPC patients with DDR or HRR pathway defects and requires further investigation.
Male ; Humans ; Prostate-Specific Antigen ; Treatment Outcome ; Prostatic Neoplasms, Castration-Resistant/drug therapy* ; Immune Checkpoint Inhibitors/therapeutic use* ; Retrospective Studies

ObjectiveTo assess the curative effects of Fangji Huangqi detumescence prescription （FHDP） on synovitis and polarization of synovial macrophages of knee osteoarthritis （KOA） model in rats induced by Hulth method. MethodThirty-six rats were randomly divided into sham operation group， model group， high-dose， medium-dose， and low-dose （29.16， 14.58， and 7.29 g·kg^-1） FHDP groups， and loxoprofen sodium （16.2 mg·kg^-1） group. KOA model in rats was induced by modified Hulth method. Six weeks after the operation， rats were given high， medium， and low concentrations of FHDP， normal saline （NS）， and loxoprofen sodium according to the group to intervene， and sacrificed after 2-week administration. Synovium and cartilage histopathological changes were observed after hematoxylin-eosin （HE） staining. Flow cytometry （FCM） and immunofluorescence （IF） test were used to evaluate the polarization of M1/M2 macrophages. Immunohistochemistry （IMC） and enzyme-linked immunosorbent assay （ELISA） were used to detect the related protein expression levels of macrophage polarization， such as interleukin-1β （IL-1β）， tumor necrosis factor-α （TNF-α）， interleukin-10 （IL-10）， and matrix metalloproteinase-13 （MMP-13） in joint tissues and serum. ResultCompared with the sham operation group， Krenn and Mankin scores in the model group were significantly increased （P<0.01）. Compared with the model group， Krenn score was decreased in all administration groups （P<0.05， P<0.01）， but there was no significant difference in Mankin score in any administration groups. Compared with the sham operation group， M1/mø （CD38⁺） ratio in the model group was significantly increased （P<0.01）， and M2/mø （CD206⁺） ratio in the model group was decreased （P<0.05）. Compared with the model group， M1/mø ratio in the high， medium， and low-dose FHDP groups was decreased （P<0.05， P<0.01）， but M2/mø ratio was increased in all administration groups （the difference had no statistical significance）. Compared with the sham operation group， M1/M2 ratio in the model group was significantly increased （P<0.01）. Compared with the model group， M1/M2 ratio in all FHDP groups was significantly decreased （P<0.01）， and M1/M2 ratio in the high and medium-dose FHDP groups was lower than that in the loxoprofen sodium group （P<0.05）. Compared with the sham operation group， the levels of TNF-α， IL-1β， and MMP-13 in synovium and cartilage of the model group were significantly increased （P<0.01）， the level of IL-10 was significantly decreased （P<0.01）. Compared with the model group， the levels of TNF-α and IL-1β in synovium were decreased in all administration groups （P<0.05）， but the difference of the levels of MMP-13 and IL-10 in synovium had no statistical significance. The level of inflammatory mediators in cartilage was not affected in all administration groups. Compared with the sham operation group， the levels of TNF-α and IL-β in serum of the model group were significantly increased （P<0.01）， the level of IL-10 was decreased （P<0.05）. Compared with the model group， the level of TNF-α in the high-dose FHDP group was decreased （P<0.05）， and the level of IL-10 was increased in all administration groups （P<0.05， P<0.01）. The difference of the level of IL-β in all administration groups had no statistical significance. ConclusionFHDP attenuated the synovitis of KOA rats. FHDP exert the effect on the releasing of proinflammatory cytokines and MMP by inhibiting the polarization of M1 macrophages in synovium， and had no significant effect on the polarization of M2 macrophages. Modulating the imbalanced polarization of synovial macrophages was a possible mechanism of FHDP on attenuating synovitis and treating KOA.

Objective:To study the early-onset epilepsy of intracerebral hemorrhage and build a prediction model to evaluate its prediction efficiency.Methods:A cross-sectional investigation was conducted to construct a specialized optimized prediction model. The prediction model was converted into a visual optimized scoring scale, so as to quantify the probability of secondary epilepsy after intracerebral hemorrhage. Based on the current prediction model of acute cerebral infraction and post-stroke seizure (AIS-PSS), the evaluation efficacy of optimized score for secondary epilepsy after hemorrhagic stroke was explored.Results:① After sample size calculation and sufficient inclusion and exclusion, 159 patients with cerebral hemorrhage were continuously selected as the model group of this cross-sectional study. A total of 29 patients with early-onset epilepsy and 130 patients without secondary epilepsy were enrolled. The time span was from January 2021 to August 2021. In addition, 77 patients with acute cerebral hemorrhage from August 2021 to February 2022 were selected as the verification group, among which 12 patients had early-onset epilepsy and 65 patients had not any secondary epilepsy. ② There were significant differences in demographic characteristics such as diabetes history, cerebral infarction history, smoking history, National Institutes of Health Stroke Scale (NIHSS) score, intracerebral hemorrhage hematoma volume, serum creatinine (SCr), neuron-specific enolase (NSE), S-100 protein and intracerebral hemorrhage site between the two model groups with different prognosis (all P < 0.05). ③ The above indexes were included in univariate and multivariate Poisson regression analysis, and the results showed that the duration of diabetes [relative risk ( RR) = 1.229, 95% confidence interval (95% CI) was 1.065-1.896, P = 0.036], smoking history ( RR = 1.419, 95% CI was 1.133-2.160, P = 0.030), history of cerebral infarction ( RR = 1.634, 95% CI was 1.128-2.548, P = 0.041), hematoma volume of cerebral hemorrhage ( RR = 1.222, 95% CI was 1.024-2.052, P = 0.041), NES content ( RR = 1.146, 95% CI was 1.041-1.704, P = 0.032), were independent influencing factors to constitute the prediction model. The prediction model was converted into a visual optimized scoring scale in the form of a line diagram to obtain the prediction probability corresponding to the corresponding score. ④ Receiver operator characteristic curve (ROC curve) was used to test the evaluation efficiency of optimized score and AIS-PSS score for early-onset cerebral hemorrhage epilepsy. Relevant data of patients in the verification group were extracted according to the information of two scores, and the final score of each patient in the verification group was obtained. The score and prognosis were put into the ROC curve to evaluate the predictive ability of different prediction models. The results showed that the cut-off value of the optimized score and the AIS-PSS score were 144 points and 7 points, respectively, and the area under the ROC curve (AUC) and the Yoden index of the optimized score were slightly lower than the AIS-PSS score. However, compared with AIS-PSS score, there was no significant difference in the evaluation efficiency of optimized score for early-onset epilepsy ( Z = 1.874, P > 0.05). Conclusion:This study constructed a specific early-onset epilepsy prediction model for patients with hemorrhagic stroke, and transformed it into an optimized score that is easy for clinical use, and its evaluation efficiency is reliable.

Professor
Acupuncture ; Acupuncture Therapy ; Angina, Stable ; Combined Modality Therapy ; Humans ; Moxibustion

Objective:To investigate the bacterial composition and antimicrobial resistance profile of clinical isolates from bloodstream infections in China.Methods:The clinical bacterial strains isolated from blood culture were collected during January 2020 to December 2020 in member hospitals of Blood Bacterial Resistant Investigation Collaborative System (BRICS). Antibiotic susceptibility tests were conducted by agar dilution or broth dilution methods recommended by Clinical Laboratory Standards Institute(CLSI, USA). WHONET 5.6 was used to analyze data.Results:During the study period, 10 043 bacterial strains were collected from 54 hospitals, of which 2 664 (26.5%) were Gram-positive bacteria and 7 379 (73.5%) were Gram-negative bacteria. The top 10 bacterial species were Escherichia coli (38.6%), Klebsiella pneumoniae (18.4%), Staphylococcus aureus (9.9%), coagulase-negative Staphylococci (7.5%), Pseudomonas aeruginosa (3.9%), Enterococcus faecium (3.3%), Enterobacter cloacae (2.8%), Enterococcus faecalis (2.6%), Acinetobacter baumannii (2.4%) and Klebsiella spp (1.8%). The prevalence of methicillin-resistant Staphylococcus aureus (MRSA) and methicillin-resistant coagulase-negative Staphylococcus aureus were 27.6% and 74.4%, respectively. No glycopeptide- and daptomycin-resistant Staphylococci were detected. More than 95% of Staphylococcus aureus were sensitive to rifampicin and SMZco. No vancomycin-resistant Enterococci strains were detected. Extended spectrum β-lactamase (ESBL) producing Escherichia coli, Klebsiella pneumoniae and Proteus mirabilis were 48.4%, 23.6% and 36.1%, respectively. The prevalence rates of carbapenem-resistance in Escherichia coli and Klebsiella pneumoniae were 2.3% and 16.1%, respectively; 9.6% of carbapenem-resistant Klebsiella pneumoniae strains were resistant to ceftazidime/avibactam combination. The prevalence rate of carbapenem-resistance in Acinetobacter baumannii was 60.0%, while polymyxin and tigecycline showed good activity against Acinetobacter baumannii. The prevalence rate of carbapenem-resistance of Pseudomonas aeruginosa was 23.2%. Conclusions:The surveillance results in 2020 showed that the main pathogens of bloodstream infection in China were gram-negative bacteria, while Escherichia coli was the most common pathogen, and ESBL-producing strains declined while carbapenem-resistant Klebsiella pneumoniae kept on high level. The proportion and the prevalence of carbapenem-resistant Pseudomonas aeruginosa were on the rise slowly. On the other side, the MRSA incidence got lower in China, while the overall prevalence of vancomycin-resistant Enterococci was low.

Objective: Several COVID-19 patients have overlapping comorbidities. The independent role of each component contributing to the risk of COVID-19 is unknown, and how some non-cardiometabolic comorbidities affect the risk of COVID-19 remains unclear. Methods: A retrospective follow-up design was adopted. A total of 1,160 laboratory-confirmed patients were enrolled from nine provinces in China. Data on comorbidities were obtained from the patients' medical records. Multivariable logistic regression models were used to estimate the odds ratio ( Results: Overall, 158 (13.6%) patients were diagnosed with severe illness and 32 (2.7%) had unfavorable outcomes. Hypertension (2.87, 1.30-6.32), type 2 diabetes (T2DM) (3.57, 2.32-5.49), cardiovascular disease (CVD) (3.78, 1.81-7.89), fatty liver disease (7.53, 1.96-28.96), hyperlipidemia (2.15, 1.26-3.67), other lung diseases (6.00, 3.01-11.96), and electrolyte imbalance (10.40, 3.00-26.10) were independently linked to increased odds of being severely ill. T2DM (6.07, 2.89-12.75), CVD (8.47, 6.03-11.89), and electrolyte imbalance (19.44, 11.47-32.96) were also strong predictors of unfavorable outcomes. Women with comorbidities were more likely to have severe disease on admission (5.46, 3.25-9.19), while men with comorbidities were more likely to have unfavorable treatment outcomes (6.58, 1.46-29.64) within two weeks. Conclusion Besides hypertension, diabetes, and CVD, fatty liver disease, hyperlipidemia, other lung diseases, and electrolyte imbalance were independent risk factors for COVID-19 severity and poor treatment outcome. Women with comorbidities were more likely to have severe disease, while men with comorbidities were more likely to have unfavorable treatment outcomes.
Adult ; Aged ; COVID-19/virology* ; China/epidemiology* ; Comorbidity ; Female ; Humans ; Male ; Middle Aged ; Retrospective Studies ; Severity of Illness Index ; Treatment Outcome

OBJECTIVE: A study was conducted to systematically evaluate the clinical efficacy of inflammatory factors in patients with chronic kidney disease and periodontitis after non-surgical periodontal therapy. METHODS: We searched the databases of CNKI, Wanfang, CBM, PubMed, Embase, and Cochrane Library from inception to December 2019. Two reviewers independently collected all literature related to inflammatory factors in patients with chronic kidney disease and periodontitis after non-surgical periodontal therapy. These factors include C-reactive protein (CRP), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α). The literature was screened according to the inclusion and exclusion criteria. The quality of the studies was strictly evaluated, and the data were extracted. The literature of randomized controlled trials in accordance with the standards was Meta-analyzed with Revman 5.3 software. RESULTS: Six randomized controlled trials were included. Compared with the control groups, the results of meta-analysis showed that non-surgical periodontal therapy significantly reduced the levels of CRP [MD=-0.58, 95%CI (-1.13, -0.02), P=0.04] and IL-6 [MD=-2.76, 95%CI (-5.15, -0.37), P=0.02] in these patients but not that of TNF-α [MD=-3.87, 95%CI (-8.79, 1.05), P=0.12]. CONCLUSIONS Simultaneous regular renal treatment and non-surgical periodontal therapy can help relieve the periodontal damage on patients with chronic kidney disease and periodontitis. Moreover, it can improve the status of some inflammatory factors. This finding is conducive to the control and treatment of chronic kidney disease and periodontitis and needs to be a focus of research and in clinical operation.
C-Reactive Protein ; Chronic Periodontitis ; Humans ; Interleukin-6 ; Renal Insufficiency, Chronic/therapy* ; Tumor Necrosis Factor-alpha