ObjectiveTo assess the predictive value of the bladder deformation index (BDI) in determining upper urinary tract (UUT) damage among patients with neurogenic bladder (NB). MethodsClinical data of 132 NB patients admitted to Beijing Bo'ai Hospital from January, 2015 to December, 2018 were retrospectively analyzed. Patients were divided into UUT damage group and normal UUT group according to the presence or absence of hydronephrosis. The demographics, biochemical parameters and video-urodynamics (VUDS) findings were collected, and BDI was calculated. Receiver operating characteristic (ROC) curves were utilized to evaluate the predictive capability. ResultsThere were 54 patients in UUT damage group and 33 in normal UUT group. The course of disease, creatinine level and BDI were siginificantly different between two groups (P < 0.05), while the area under the curve were 0.686, 0.836 and 0.928, respectively. ConclusionCourse of disease, creatinine level and BDI are associated with UUT damage in NB patients, and BDI demonstrates the highest sensitivity and specificity, which may play a role in diagnosis of UUT damage.

Traditional development of small protein scaffolds has relied on display technologies and mutation-based engineering, which limit sequence and functional diversity, thereby constraining their therapeutic and application potential. Protein design tools have significantly advanced the creation of novel protein sequences, structures, and functions. However, further improvements in design strategies are still needed to more efficiently optimize the functional performance of protein-based drugs and enhance their druggability. Here, we extended an evolution-based design protocol to create a novel minibinder, BindHer, against the human epidermal growth factor receptor 2 (HER2). It not only exhibits super stability and binding selectivity but also demonstrates remarkable properties in tissue specificity. Radiolabeling experiments with ^99mTc, ⁶⁸Ga, and ¹⁸F revealed that BindHer efficiently targets tumors in HER2-positive breast cancer mouse models, with minimal nonspecific liver absorption, outperforming scaffolds designed through traditional engineering. These findings highlight a new rational approach to automated protein design, offering significant potential for large-scale applications in therapeutic mini-protein development.

OBJECTIVE: EPF3 is a fibrinolysin monomer isolated and purified from Pheretima vulgaris Chen, an earthworm used in traditional Chinese medicine as Dilong for treating blood stasis syndrome. Its composition, anticoagulant and fibrinolytic activities, and relevant mechanisms have been confirmed through in vitro experiments. However, whether it has antithrombotic effects in vivo and can be absorbed by the gastrointestinal tract is unknown. This study evaluates the antithrombotic effect in zebrafish and investigates the gastrointestinal stability and intestinal absorption mechanism of this protein in vitro. METHODS: The antithrombotic effect of EPF3 in vivo was verified using the zebrafish thrombus model induced by arachidonic acid and FeCl₃. Then, the protein bands of EPF3 incubated with simulated gastric fluid (SGF), simulated intestinal fluid (SIF), and homogenate of Caco-2 cells (HC2C) were analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis to evaluate its gastrointestinal stability. Finally, the transport behavior and absorption mechanism of EPF3 were studied using Caco-2 cell monolayer. RESULTS: EPF3 could significantly enhance the returned blood volume and blood flow velocity in zebrafish with platelet aggregation thrombus induced by arachidonic acid. It could also prolong the formation time of tail artery thrombus and increase the blood flow velocity in zebrafish with vessel injury thrombus induced by FeCl₃. EPF3 was stable in SIF and HC2C and unstable in SGF. The permeability of EPF3 in Caco-2 monolayer was time-dependent and concentration-dependent. The efflux ratio was less than 1.2 during transport, and the transport behavior was not affected by inhibitors. EPF3 could reversibly reduce the expression of tight junction-related proteins, including zonula occludens-1, occludin, and claudin-1 in Caco-2 cells. CONCLUSION EPF3 could play a thrombolytic and antithrombotic role in zebrafish. It could be transported and absorbed into the intestine through cellular bypass pathway by opening the intestinal epithelium tight junction. This study provides a scientific explanation for the antithrombotic effect of earthworm and provides a basis for the feasibility of subsequent development of EPF3 as an antithrombotic enteric-soluble preparation. Please cite this article as: Zhong WL, Yang JQ, Liu H, Wu YL, Shen HJ, Li PY, Du SY. Antithrombotic effect in zebrafish of a fibrinolytic protein EPF3 from Dilong (Pheretima vulgaris Chen) and its transport mechanism in Caco-2 monolayer through cell bypass pathway. J Integr Med. 2025; 23(4): 415-428.
Animals ; Zebrafish ; Humans ; Caco-2 Cells ; Fibrinolytic Agents/pharmacology* ; Thrombosis/drug therapy* ; Intestinal Absorption

Human brain banks use a standardized protocol to collect,process and store post-mortem human brains and related tissues,along with relevant clinical information,and to provide the tissue samples and data as a resource to foster neuroscience research according to a standardized operating protocols(SOP).Human brain bank serves as the foundation for neuroscience research and the diagnosis of neurological disorders,highlighting the crucial rule of ensuring the consistency of standardized quality for brain tissue samples.The first version of SOP in 2017 was published by the China Human Brain Bank Consortium.As members increases from different regions in China,a revised SOP was drafted by experts from the China Human Brain Bank Consortium to meet the growing demands for neuroscience research.The revised SOP places a strong emphasis on ethical standards,incorporates neuropathological evaluation of brain regions,and provides clarity on spinal cord sampling and pathological assessment.Notable enhancements in this updated version of the SOP include reinforced ethical guidelines,inclusion of matching controls in recruitment,and expansion of brain regions to be sampled for neuropathological evaluation.

Objective By population survey,to explore the epidemiological characteristics of gastric precancerous lesions in Lishui District of Nanjing and provide objective basis for the prevention and treatment of early gastric cancer.Methods From July 2021 to December 2022,21 977 patients who received endoscopy and/or 13C-UBT in Lishui District People's Hospital and 6 medical community units in Nanjing City were retrospectively analyzed for demography characteristics,detection rate of gastric precancerous lesions,and H.Pylori infection rate.Results(1)590 cases of gastric precancerous lesions were detected(detection rate 2.68%);(2)The total detection rate of precancerous lesions and three pathological types in males were all higher than those in females(all P<0.001);(3)The minimum age for the total detection rate of precancerous lesions in males and the mini-mum age for each pathological type were lower than in females(P<0.001,0.009,0.005,0.002);(4)The popu-lation total H.pylori infection rate was 23.10%,the H.pylori infection rate in patients with precancerous lesions was higher than that in non-precancerous lesions(P<0.001),both H.pylori infection rate of male and female in precancerous lesions were all higher than those of non-precancerous lesions of the same sex(all P<0.001),in addition,the H.pylori infection rate of male whether in precancerous or non-precancerous lesions was higher than that of female(all P<0.001);(5)The precancerous lesions detection rate in male,female,and the overall age range of 20～29 to 70～79 years is positively correlated with age growth(P<0.001),and rapidly decreases after the age of 79,the of H.pylori infection rate was also positively correlated with age growth(P<0.001),and the trend of age change(P<0.001)was parallel to the precancerous lesions detection rate.Conclusions The detec-tion rate of gastric precancerous lesions in this region is above the average level in China;the total H.pylori infec-tion rate is at a relatively low level in China;the H.pylori infection rate is parallel to the age trend of the detection rate of gastric precancerous lesions,and increases with age.

Objective:To investigate the prevalence of hyperuricemia (HUA) in Bozidun Kirghiz township of Xinjiang Aksu region, and to explore the risk factors for the occurrence of HUA in the local area.Methods:A cross-sectional survey study was conducted by randomly selecting 9 villages in Bozidun Kirgiz Township by the whole-group sampling method and questionnaire were distributed to the households. The questionnaire included: demographic information, history of past illness, personal history, and all subjects were measured for height, weight, blood pressure, abdominal circumference, etc. The diagnostic of HUA if the serum uric acid (SUA) level >420 μmol/L in men or >360 μmol/L in women. The incidences of HUA in different age, sex, food type and life style behavior were analyzed. T test, non-parametric test and Chi-square test were used to analyze the differences among the groups, and logistic regression was used to analyze the risk factors. Results:①A total of 2 138 subjects were surveyed, among which 68 patients were with HUA, the prevalence of HUA in Bozidun Kirghiz township, Aksu region in the general population was 3.18%(68/2 138); the prevalence rate in men was 4.60%(45/978), 45 patients were identified; and the prevalence rate in women was 1.98%(23/1 160), 23 patients were identified. The peak age of HUA in male and female patients was 51~60 years old. ②The prevalence of HUA was lower in those who consumed dairy products ( χ2=6.91, P=0.017), nuts ( χ2=8.43, P=0.038) and eggs ( χ2=7.38, P=0.023), and lower in those who consumed more. Different intake of cereals ( χ2=0.87, P=0.647), meat( χ2=0.82, P=0.662), vegetables and fruits( χ2=5.22, P=0.073) had no effect on the prevalence of HUA.③In terms of different life behaviors, the prevalence of HUA in men who had been smoking was higher than those who had never smoked (57.78%, 28.89%, 13.33%, χ2=8.16, P=0.017). In the relationship between drinking and HUA, the prevalence rates of male always drinking, ever drinking and never drinking were 80.00%, 11.11% and 3.89%, respectively, the difference was statistically significant ( χ2=6.67, P=0.038). ④Multi-factor logistic regression analysis showed that high BMI, old age, high TG, increased Cr and increased WBC were risk factors for the occurrence of HUA [ OR(95% CI)=1.13(1.04, 1.23), 1.03(1.00,1.05),1.39(1.00, 1.93), 1.03(1.02, 1.05), 1.27(1.07, 1.49), all P<0.05]. Conclusion:The prevalence of HUA in Bozidun Kirgiz township in Aksu prefecture of Xinjiang is lower than that in other areas with continental climate. High BMI, old age, high TG, increased Cr and increased WBC count are risk factors for the development of HUA .

Polycystic ovary syndrome(PCOS)is a common endocrine and metabolic disease in gynecology.The main clinical manifestations are infertility,hirsuty,obesity,menstrual disorders,etc.,which seriously affect women's health.Studies have shown that the mechanism of action of traditional Chinese medicine in the treatment of PCOS involves a variety of signaling pathways,among which advanced glycation end products-receptor for advanced glycation end products(AGE-RAGE)signaling pathway is an important pathway regulating inflammation and oxidative stress.More and more Chinese herbal compounds,single herbs and their extracts can reduce inflammation,oxidative stress,insulin resistance and hyperandrogenemia in patients by regulating AGE-RAGE signaling pathway,which provides a new strategy and direction for the treatment of PCOS.However,there is currently no comprehensive summary of Chinese medicine intervention in the treatment of PCOS by AGE-RAGE signaling pathway.Therefore,this paper reviews the current research status of Chinese medicine regulation of AGE-RAGE signaling pathway in the treatment of PCOS in recent years,so as to provide new directions and thoughts for further research on PCOS.

Objective:To analyze the clinical characteristics of idiopathic systemic capillary leak syndrome (ISCLS).Methods:This retrospective case series analysis included 10 patients with confirmed ISCLS who were hospitalized at Peking Union Medical College Hospital from January 1983 to August 2023. Data collected encompassed general information, symptoms, laboratory results, treatment, and prognosis.Results:Among 10 ISCLS patients, 8 were males and 2 were females. The age of onset ranged from 29 to 63 years, and it was ≥40 years in 6 cases. Nine patients had nonspecific prodromal symptoms. All 10 experienced hypotension, hemoconcentration, hypoalbuminemia, and acute kidney injury during the leakage phase, with hemodynamic recovery in the subsequent phase. Neurological abnormalities were observed in 6 patients. Three patients had coagulation disorders, and 4 showed elevated levels of IL-6, IL-8, and TNF-α. M protein was found in all patients, with 8 showing IgGκ and 2 IgGλ. Acute-phase treatment primarily involved fluid resuscitation and vasopressors. In the stable phase, 4 patients had fewer episodes with anti-plasma cell therapy; 2 continued to have episodes despite intravenous immunoglobulin (IVIG); 2 had poor outcomes with theophylline; 1 improved without treatment; and 1 was lost to follow-up.Conclusions:ISCLS is a rare disease with adult-onset, presenting nonspecific prodromal symptoms and marked hypotension during episodes. All patients had monoclonal gammopathy. Effective treatment for the stable phase is lacking, though anti-plasma cell therapy may offer some benefit.

Objective To investigate the distribution and antimicrobial resistance profiles of the common pathogens isolated from urine from 2015 to 2021 in the CHINET Antimicrobial Resistance Surveillance Program.Methods The bacterial strains were isolated from urine and identified routinely in 51 hospitals across China in the CHINET Antimicrobial Resistance Surveillance Program from 2015 to 2021.Antimicrobial susceptibility was determined by Kirby-Bauer method,automatic microbiological analysis system and E-test according to the unified protocol.Results A total of 261 893 nonduplicate strains were isolated from urine specimen from 2015 to 2021,of which gram-positive bacteria accounted for 23.8％(62 219/261 893),and gram-negative bacteria 76.2％(199 674/261 893).The most common species were E.coli(46.7％),E.faecium(10.4％),K.pneumoniae(9.8％),E.faecalis(8.7％),P.mirabilis(3.5％),P.aeruginosa(3.4％),SS.agalactiae(2.6％),and E.cloacae(2.1％).The strains were more frequently isolated from inpatients versus outpatients and emergency patients,from females versus males,and from adults versus children.The prevalence of ESBLs-producing strains in E.coli,K.pneumoniae and P.mirabilis was 53.2％,52.8％and 37.0％,respectively.The prevalence of carbapenem-resistant strains in E.coli,K.pneumoniae,P.aeruginosa and A.baumannii was 1.7％,18.5％,16.4％,and 40.3％,respectively.Lower than 10％of the E.faecalis isolates were resistant to ampicillin,nitrofurantoin,linezolid,vancomycin,teicoplanin and fosfomycin.More than 90％of the E.faecium isolates were ressitant to ampicillin,levofloxacin and erythromycin.The percentage of strains resistant to vancomycin,linezolid or teicoplanin was＜2％.The E.coli,K.pneumoniae,P.aeruginosa and A.baumannii strains isolated from ICU inpatients showed significantly higher resistance rates than the corresponding strains isolated from outpatients and non-ICU inpatients.Conclusions E.coli,Enterococcus and K.pneumoniae are the most common pathogens in urinary tract infection.The bacterial species and antimicrobial resistance of urinary isolates vary with different populations.More attention should be paid to antimicrobial resistance surveillance and reduce the irrational use of antimicrobial agents.

Objective To understand the distribution and changing resistance profiles of clinical isolates of Enterococcus in hospitals across China from 2015 to 2021.Methods Antimicrobial susceptibility testing was conducted for the clinical isolates of Enterococcus according to the unified protocol of CHINET program by automated systems,Kirby-Bauer method,or E-test strip.The results were interpreted according to the Clinical & Laboratory Standards Institute(CLSI)breakpoints in 2021.WHONET 5.6 software was used for statistical analysis.Results A total of 124 565 strains of Enterococcus were isolated during the 7-year period,mainly including Enterococcus faecalis(50.7％)and Enterococcus faecalis(41.5％).The strains were mainly isolated from urinary tract specimens(46.9％±2.6％),and primarily from the patients in the department of internal medicine,surgery and ICU.E.faecium and E.faecalis strains showed low level resistance rate to vancomycin,teicoplanin and linezolid(≤3.6％).The prevalence of vancomycin-resistant E.faecalis and E.faecium was 0.1％and 1.3％,respectively.The prevalence of linezolid-resistant E.faecalis increased from 0.7％in 2015 to 3.4％in 2021,while the prevalence of linezolid-resistant E.faecium was 0.3％.Conclusions The clinical isolates of Enterococcus were still highly susceptible to vancomycin,teicoplanin,and linezolid,evidenced by a low resistance rate.However,the prevalence of linezolid-resistant E.faecalis was increasing during the 7-year period.It is necessary to strengthen antimicrobial resistance surveillance to effectively identify the emergence of antibiotic-resistant bacteria and curb the spread of resistant pathogens.