Prostate cancer is the most prevalent malignant tumor among men, ranking first in incidence and second in mortality globally. Novel hormone therapies (NHT) targeting the androgen receptor (AR) pathway have become the standard of care for metastatic prostate cancer. This review offers a comprehensive overview of NHT, including abiraterone, enzalutamide, apalutamide, darolutamide, and rezvilutamide, which have demonstrated efficacy in delaying disease progression and improving patient survival and quality of life. Nevertheless, resistance to NHT remains a critical challenge. The mechanisms underlying resistance are complex, involving AR gene amplification, mutations, splice variants, increased intratumoral androgens, and AR-independent pathways such as the glucocorticoid receptor, neuroendocrine differentiation, DNA repair defects, autophagy, immune evasion, and activation of alternative signaling pathways. This review discusses these resistance mechanisms and examines strategies to counteract them, including sequential treatment with novel AR-targeted drugs, chemotherapy, poly ADP-ribose polymerase inhibitors, radionuclide therapy, bipolar androgen therapy, and approaches targeting specific resistance pathways. Future research should prioritize elucidating the molecular basis of NHT resistance, optimizing existing therapeutic strategies, and developing more effective combination regimens. Additionally, advanced sequencing technologies and resistance research models should be leveraged to identify novel therapeutic targets and improve drug delivery efficiencies. These advancements hold the potential to overcome NHT resistance and significantly enhance the management and prognosis of patients with advanced prostate cancer.

OBJECTIVE: Emerging evidence suggests that exposure to ultrafine particulate matter (UPM, aerodynamic diameter < 0.1 µm) is associated with adverse cardiovascular events. Previous studies have found that Shenlian (SL) extract possesses anti-inflammatory and antiapoptotic properties and has a promising protective effect at all stages of the atherosclerotic disease process. In this study, we aimed to investigated whether SL improves UPM-aggravated myocardial ischemic injury by inhibiting inflammation and cell apoptosis. METHODS: We established a mouse model of MI+UPM. Echocardiographic measurement, measurement of myocardialinfarct size, biochemical analysis, enzyme-linked immunosorbent assay (ELISA), histopathological analysis, Transferase dUTP Nick End Labeling (TUNEL), Western blotting (WB), Polymerase Chain Reaction (PCR) and so on were used to explore the anti-inflammatory and anti-apoptotic effects of SL in vivo and in vitro. RESULTS: SL treatment can attenuate UPM-induced cardiac dysfunction by improving left ventricular ejection fraction, fractional shortening, and decreasing cardiac infarction area. SL significantly reduced the levels of myocardial enzymes and attenuated UPM-induced morphological alterations. Moreover, SL significantly reduced expression levels of the inflammatory cytokines IL-6, TNF-α, and MCP-1. UPM further increased the infiltration of macrophages in myocardial tissue, whereas SL intervention reversed this phenomenon. UPM also triggered myocardial apoptosis, which was markedly attenuated by SL treatment. The results of in vitro experiments revealed that SL prevented cell damage caused by exposure to UPM combined with hypoxia by reducing the expression of the inflammatory factor NF-κB and inhibiting apoptosis in H9c2 cells. CONCLUSION Overall, both in vivo and in vitro experiments demonstrated that SL attenuated UPM-aggravated myocardial ischemic injury by inhibiting inflammation and cell apoptosis. The mechanisms were related to the downregulation of macrophages infiltrating heart tissues.
Animals ; Apoptosis/drug effects* ; Particulate Matter/adverse effects* ; Mice ; Male ; Inflammation/drug therapy* ; Drugs, Chinese Herbal/therapeutic use* ; Mice, Inbred C57BL ; Myocardial Ischemia/drug therapy* ; Cell Line

Objective To evaluate the efficacy,safety,and cost-effectiveness of berberine-based quadruple therapy vs.the clarithromycin-based quadruple therapy for Helicobacter pylori(H.pylori)eradication in treatment-na?ve patients.Methods This was a single-center,prospective,open-label randomized controlled trial.A total of 404 treatment-naive patients with H.pylori infection who visited the Outpatient Department of Gastroenterology,the First Medical Center of Chinese PLA General Hospital from September 2021 to May 2024 were enrolled.The patients were randomly assigned in a 1:1 ratio to two groups:berberine quadruple therapy group(berberine+amoxicillin+esomeprazole+colloidal bismuth pectin;n=202)and clarithromycin quadruple therapy group(clarithromycin+amoxicillin+esomeprazole+colloidal bismuth pectin;n=202).Both groups received a 14-day treatment course.The H.pylori eradication rate,incidence of adverse reactions,medication compliance,and treatment costs were compared between the two groups.Results By intention-to-treat(ITT)analysis,eradication rate did not differ significantly between the two groups[89.1%(180/202)in berberine quadruple therapy group vs.89.6%(181/202)in clarithromycin quadruple therapy group,P=0.872].The per-protocol(PP)analysis also showed no significant difference in the eradication rate between the two groups[90.4%(179/198)vs.91.3%(178/195),P=0.763].The incidence of adverse reactions in berberine quadruple therapy group was significantly lower than that in clarithromycin quadruple therapy group[18.2%(36/198)vs.38.5%(75/195),P<0.001].Specifically,the incidence of taste disturbance in berberine quadruple therapy group was significantly lower than that in clarithromycin quadruple therapy group(3.0%vs.15.4%,P<0.001).There was no statistically significant difference in medication compliance between the two groups[98.5%(195/198)in berberine quadruple therapy group vs.97.9%(191/195)in clarithromycin quadruple therapy group,P=0.688].The fixed direct medical cost per patient was significantly lower in berberine quadruple therapy group than that in clarithromycin quadruple therapy group(402.08 yuan vs.693.94 yuan).Conclusions The berberine-based quadruple therapy is as effective as traditional clarithromycin-based quadruple therapy for eradicating H.pylori,with the advantages of a lower incidence of adverse reactions and lower cost.It represents a safe,effective,and economical treatment option worthy of further promotion and application.

Malaria, one of the major global public health events, is a leading cause of mortality and morbidity among children and adults in tropical and subtropical regions(mainly in sub-Saharan Africa), threatening human health. It is well known that malaria can cause various complications including anemia, blackwater fever, cerebral malaria, and kidney damage. Conventionally, cardiac involvement has not been listed as a common reason affecting morbidity and mortality of malaria, which may be related to ignored cases or insufficient diagnosis. However, the serious clinical consequences such as acute coronary syndrome, heart failure, and malignant arrhythmia caused by malaria have aroused great concern. At present, antimalarials are commonly used for treating malaria in clinical practice. However, inappropriate medication can increase the risk of cardiovascular diseases and cause severe consequences. This review summarized the research advances in the cardiovascular complications including acute myocardial infarction, arrhythmia, hypertension, heart failure, and myocarditis in malaria. The possible mechanisms of cardiovascular diseases caused by malaria were systematically expounded from the hypotheses of cell adhesion, inflammation and cytokines, myocardial apoptosis induced by plasmodium toxin, cardiac injury secondary to acute renal failure, and thrombosis. Furthermore, the effects of quinolines, nucleoprotein synthesis inhibitors, and artemisinin and its derivatives on cardiac structure and function were summarized. Compared with the cardiac toxicity of quinolines in antimalarial therapy, the adverse effects of artemisinin-derived drugs on heart have not been reported in clinical studies. More importantly, the artemisinin-derived drugs demonstrate favorable application prospects in the prevention and treatment of cardiovascular diseases, and are expected to play a role in the treatment of malaria patients with cardiovascular diseases. This review provides reference for the prevention and treatment of malaria-related cardiovascular complications as well as the safe application of antimalarials.
Child ; Adult ; Humans ; Antimalarials/pharmacology* ; Cardiovascular Diseases/drug therapy* ; Artemisinins/pharmacology* ; Quinolines ; Malaria, Cerebral/drug therapy* ; Heart Failure/drug therapy* ; Arrhythmias, Cardiac/drug therapy*

BACKGROUND: Glucose control is an important aspect in managing critically ill patients. The goal of this study was to compare the effects of sequential feeding (SF) and continuous feeding (CF) on the blood glucose of critically ill patients. METHODS: A non-inferiority randomized controlled trial was adopted in this study. A total of 62 patients who were fed enteral nutritional suspension through gastric tubes were enrolled. After achieving 80% of the nutrition target calories (25 kcal·kg-1·day-1) through CF, the patients were then randomly assigned into SF and CF groups. In the SF group, the feeding/fasting time was reasonably determined according to the circadian rhythm of the human body as laid out in traditional Chinese medicine theory. The total daily dosage of the enteral nutritional suspension was equally distributed among three time periods of 7 to 9 o'clock, 11 to 13 o'clock, and 17 to 19 o'clock. The enteral nutritional suspension in each time period was pumped at a uniform rate within 2 h by an enteral feeding pump. In the CF group, patients received CF at a constant velocity by an enteral feeding pump throughout the study. Blood glucose values at five points (6:00/11:00/15:00/21:00/1:00) were monitored and recorded for seven consecutive days after randomization. Enteral feeding intolerance was also recorded. Non-inferiority testing was adopted in this study, the chi-square test or Fisher test was used for qualitative data, and the Mann-Whitney U test was used for quantitative data to determine differences between groups. In particular, a repeated measure one-way analysis of variance was used to identify whether changes in glucose value variables across the time points were different between the two groups. RESULTS: There were no significant demographic or physiological differences between the SF and CF groups (P > 0.050). The average glucose level in SF was not higher than that in CF (8.8 [7.3-10.3] vs. 10.7 [9.1-12.1] mmol/L, Z = -2.079, P for non-inferiority = 0.019). Hyperglycemia incidence of each patient was more common in the CF group than that in the SF group (38.4 [19.1-63.7]% vs. 11.8 [3.0-36.7]%, Z = -2.213, P = 0.027). Hypoglycemia was not found in either group. Moreover, there was no significant difference during the 7 days in the incidence of feeding intolerance (P > 0.050). CONCLUSIONS: In this non-inferiority study, the average blood glucose in SF was not inferior to that in CF. The feeding intolerance in SF was similar to that in CF. SF may be as safe as CF for critically ill patients. TRIAL REGISTRATION ClinicalTrials.gov, NCT03439618; https://clinicaltrials.gov/ct2/show/record/NCT03439618.
Blood Glucose ; Critical Illness ; Energy Intake ; Enteral Nutrition ; Humans ; Hyperglycemia ; Infant, Newborn

Objective To analyze morbidity,mortality and epidemiological characteristics of epidemic encephalitis B (Japanese encephalitis) from 2002 to 2013 in Zunyi.Methods The descriptive and statistical analysis of the incidence and death of epidemic encephalitis B from 2002 to 2013 in Zunyi was carried out.Results The morbidity and mortality were on a downward trend of epidemic encephalitis B in Zunyi from 2002 to 2013;most of the death and incidence cases occurred in July and August from children living scattered and students under age 15;after immunization expansion,the incidence of encephalitis B showed significant differences between ages,occupations,and time points (P<0.05);in the regional distribution of epidemic encephalitis B,incidence and mortality had significant differences (P<0.05).Conclusion Promising results might be generally obtained after expansion of encephalitis B immunization.However,there is a tendency of shifting back in terms of onset age and month.Therefore,comprehensive prevention measures should be implemented according to the epidemiological features of epidemic encephalitis B.

Objective To explore the association between Q-1 and T1 locus polymorphism in ADAM33 gene and chronic obstructive pulmonary disease in Han population in northern Guizhou by detecting Q-1 and T1 locus polymorphism in ADAM33 gene in patients with COPD in the distribution of frequency ,provide a theoretical basis for the prevention and treatment of COPD. Methods Polymerase chain reaction and DNA sequencing tech-nology,electrophoresis separation method were applied to detect Q-1 and T1 locus polymorphism in ADAM33 gene. Results The genotype distribution of Q-1 and T1 locus in the case group and the control group of ADAM33 gene were in accordance with the Hardy-Weinberg equilibrium law and ADAM33 gene Q-1,T1 locus were C and T alleles. There was no significant difference in genotype and allele frequency distribution between the case group with control group,and COPD complicated with chronic respiratory failure(COPD)and hypoxemia(P > 0.05). T1(83 bp,112 bp)at a high probability of two heterozygous in the same samples(18/19),and is located in the encoding region. Conclusion No association was found between Q-1,T1 locus polymorphism in ADAM33 gene and chronic obstructive pulmonary disease in Han population in northern Guizhou.

Objective To investigate the effect of indoor coal PM2.5 on the airway inflammation and the pathological morphology alterations of lung tissue in asthmatic rats induced by ovalbumin(OVA). Methods Forty six?week?old male SD rats were randomly divided into four groups(Control,OVA,PM2.5,PM2.5+OVA). Normal saline,OVA(15μg/mL)and(or)PM2.5(2.5 mg/mL)were given to rats in the four groups through intratracheal instillation for four times (two weeks one time),respectively. Twenty?four hours after the last intratracheal instillation ,bronchoalveolar irrigation lavage fluid (BALF) was collected for determinations of serum interleukin 4(IL?4),interferon gamma (IFN?γ). The lung tissue was collected for HE staining and electron microscopy detection. Results HE staining showed less inflammatory cell infiltration was observed in the control group;In PM2.5 group and OVA group,there was medium quantity of inflammatory cell infiltration,In PM2.5+OVA group, severe inflammatory cell infiltration was observed. Electron microscopy showed no abnormal lung tissue in the control group,but organelles were gradually destroyed,endothelial cell edama,alveolar interval with a large number of fibersin were observed in PM2.5 group. The exfoliated cells,local typeⅡ cells with visible damage were found in OVA group. A large number of fibers were existed among the lung tissues and organelles were destroyed,thickness of basement membrane was non?uniform,and blood air barrier structure was not clear in PM2.5 + OVA group. Compared with PM2.5+OVA group,concentration of IL?4 in PM2.5,OVA and the control group was siganificantly different(P < 0.05). A negative correlation between IL?4 and IFN?γ was observed (r =-0.358,P < 0.05). Conclusion Indoor coal PM2.5 exacerbates the airway inflammatory cell infiltration and airway remodeling in OVA?induced asthmatic rats.

OBJECTIVETo investigate surgical procedure and clinical effects for the treatment of patellofemoral osteoarthritis (PFOA) with arthroscopic patelloplasty and circumpatellar denervation.

METHODSTotally 156 patients with PFOA (62 males and 94 females; aged from 45 to 61 years old with an average of 52) were treated from September 2011 and March 2013. The clinical manifestations included recurrent swelling and pains on knee-joint,and aggravated pains upon going up/down-stairs, squatting-down, or standing-up. PFOAs were treated with arthroscopic patelloplasty and circumpatellar denervation. The therapeutic effects before and after surgery were evaluated by Lysholm scores and Kujala scores. The therapeutic effects were graded by classification of cartilage injury degrees.

RESULTSTotally 149 cases were successfully followed up for 14.8 months. The incisions were healed well and no complication were occurred. Lysholm score was improved from 73.29 preoperatively to 80.93 postoperatively and average Kajala score from 68.34 preoperatively to 76.48 after surgery. This procedure was highly effective for patients with I - III degree cartilage injury, while not for patients with IV degree cartilage injury.

CONCLUSIONFor PFOA patients, arthroscopic patelloplasty and circumpatellar denervation is effective for significantly relieving anterior knee pains, improving knee-joint functions and quality of life, and deferring arthritic procession.

Arthroscopy ; Denervation ; Female ; Humans ; Knee Joint ; innervation ; surgery ; Male ; Middle Aged ; Osteoarthritis, Knee ; physiopathology ; surgery ; Range of Motion, Articular ; Treatment Outcome

OBJECTIVETo explore the effectiveness of hamstring tendon graft embedding reconstruction of medial patellofemoral ligament for the treatment of recurrent dislocation of the patella.

METHODSFrom March 2008 to June 2013,67 patients with recurrent dislocation of patella were treated, including 28 males, 39 females with an average age of 22 years ranging from 10 to 42 years old. The clinical manifestations involved knee joint instability,"giving way", sense of patellar dislocation, anterior knee pain. All 67 patients underwent arthroscopic hamstring tendon graft embedding reconstruction of the medial patellofemoral ligament. The curative effect were evaluated by preoperative and postoperative Lysholm score and Q angle changes.

RESULTSAll cases were followed up after operation and the mean follow-up time was(27.5±13.4) months(4 to 69 months). Postoperative incision were healed well and no patellar dislocation or subluxation occurred. Lysholm score improved from preoperative 76.35±2.86 to 82.71±2.29 postoperatively; Q angle decreased from preoperative (18.75±2.33)° to postoperative(13.28±1.75)°.

CONCLUSIONThe method for the reconstruction of medial patellofemoral ligament can provide enough tension, patellar stability.imoroving the function of knee ioint.

Adolescent ; Adult ; Child ; Female ; Humans ; Male ; Patellar Dislocation ; surgery ; Patellar Ligament ; surgery ; Patellofemoral Joint ; surgery ; Reconstructive Surgical Procedures ; methods ; Recurrence ; Tendons ; transplantation