1.Research progress of urea-containing PET tracers targeting prostate specific membrane antigen
Hong ZHU ; Hui WANG ; Hongwei SI ; Dan ZHANG ; Dengyun CHEN ; Pengfei DAI
Acta Universitatis Medicinalis Anhui 2026;61(2):369-375
Prostate cancer is one of the most common malignant tumors of male genitourinary system. Prostate cancer has the following characteristics: insidious onset, early asymptomatic or not obvious symptoms, complex etiology and pathogenesis, long incubation period and so on. Therefore, the realization of its early diagnosis and treatment is of great significance to the prognosis of patients. Prostate-specific membrane antigen (PSMA) is a type 2 transmembrane glycoprotein that is highly expressed on the membrane of almost all primary and metastatic prostate cancer cells, and is an ideal target for prostate cancer imaging and treatment. In recent years, with the approval of urea-containing small molecule PET (positron emission computed tomography) radiopharmaceutical based on PSMA (68Ga-PSMA-11, 18F-PSMA-1007), PET-CT (positron emission computed tomography/computed tomography) has shown new potential for early diagnosis and accurate staging of prostate cancer patients. This review mainly summarizes the research progress of urea-containing PSMA PET imaging agents and finds that they have defects such as uptake in non-target tissues like the kidneys, lacrimal glands, and salivary glands. Thus, further optimizing their structure to reduce the uptake in non-target tissues, providing provide convenience for the labeling of therapeutic radiopharmaceuticals, thereby achieving the goal of integrated diagnosis and treatment, is an important development direction in this field.
2.Identification and infection rate of densovirus in Culex pipiens pallens in Beijing in 2023
Xiu-yan XU ; Ting YAN ; Si-jie ZHU ; Jing LI ; Mei-de LIU ; Hong-jiang ZHANG ; Ting LIU ; Qiu-hong LI ; Xiao-jie ZHOU ; Ying TONG ; Yong ZHANG
Acta Parasitologica et Medica Entomologica Sinica 2026;33(1):25-30
Objective This study conducted molecular biological identification of the viruses carried by Culex pipiens pallens specimens collected in Shunyi District, Beijing in 2023, and observed the changes in the infection rate of the viruses carried by Cx. pipiens pallens at different collection times. Methods Cx. pipiens pallens were collected using carbon dioxide mosquito traps. The mosquito samples were ground in batches and analyzed by molecular biology technologies. The virus infection rate at different collection times was analyzed statistically. Results 17 strains of Culex pipiens pallens densovirus(CppDNV)were identified from Cx. pipiens pallens samples collected in Shunyi District, Beijing, in 2023. The nucleotide sequence analysis of the virus genome coding region showed that CppDNV was a single-stranded DNA virus with a total length of 3 335 nt, encoding 2 non-structural proteins(NS1, NS2)and 1 capsid protein(VP). The nucleotide(amino acid)sequence lengths of the three proteins were 2 376 nt(791 aa),1 092 nt(363 aa)and 1 071 nt(356 aa), respectively. Phylogenetic analysis showed that CppDNV was located in genus Brevihamaparvovirus. Statistical analysis showed no significant difference in infection rates across collection times(χ2=4.429, P=0.194). Conclusions CppDNV was identified in Cx. pipiens pallens in Beijing, and it was stably maintained in this natural population.
3.Mosquito monitoring and influence of meteorological factors on mosquito density around Beijing Capital International Airport, 2016-2022
Ran FENG ; Tie-zheng MA ; Si-jie ZHU ; Bo TIAN ; Fei QUAN ; Zhi-lin WU ; Xiao-tao LIU ; Fu-yuan ZHANG ; Song-jian ZHANG
Acta Parasitologica et Medica Entomologica Sinica 2026;33(1):40-48
Objective To understand mosquito density, species composition, and seasonal variations around the Beijing Capital International Airport(BCIA)and provide scientific evidence for mosquito-borne disease prevention and control. Methods Meteorological data were collected from 2016 to 2022, and mosquito density was monitored at seven surveillance sites around the BCIA from May to October each year using CO2-baited mosquito traps to analyze the relationship between mosquito density and meteorological factors. Results In total,68 518 female mosquitoes were captured, with a mosquito density of 10.20 per light · hour. The dominant species was Culex pipiens pallens(73.90%), followed by Aedes albopictus(9.71%)and Ae. vexans(9.29%);the mosquito density was highest in 2016(14.8 per light·hour)and lowest in 2022(4.46 per light·hour). Significant statistical differences were observed in mosquito density among different species(F=18.118, P<0.05). The density of Cx. pipiens pallens and other mosquito species showed a mutually exclusive trend; the peak of mosquito density varied based on years and habitats, with significant statistical differences in mosquito density among different habitats(F=8.504, P<0.05). The highest mosquito density was observed near the Wenyu River(21.50 per light·hour), whereas the lowest was recorded at the BCIA construction site(2.44 per light· hour). The monthly average temperature(r=0.595), monthly average highest temperature(r=0.575), and monthly average lowest temperature(r=0.624)showed moderate positive correlations, whereas the monthly average air pressure(r=-0.484)showed a moderate negative correlation. The monthly average minimum temperature was included in the regression model(F=25.575, P<0.000), and the equation Y=1.029X4-8.181 was used. The monthly average air pressure 2 months prior(b=-2.418, β=-1.619, P<0.05)and the monthly average relative humidity(b=-0.739, β=-1.201, P<0.05)significantly negatively predicted the mosquito density. Notably, the regression equation used was y=2526.170+(-2.418)X9+(-0.739)X13. The exposure-response analysis revealed that the density of mosquitoes was not linearly related to the average monthly air pressure, rainfall, and duration of sunshine. Conclusions The dominant mosquito species around the BCIA was Cx. pipiens pallens, Ae. albopictus, and Ae. vexans. During the control of Cx. pipiens pallens, the impact on other mosquito species must also be considered. Environmental management, breeding sites, and scientific use of pesticides should be prioritized based on the activity periods of mosquitoes. Further studies on mosquitoes and meteorological factors should be conducted to provide references and novel avenues for mosquito control.
4.Clinical features analysis of patients with inflammatory bowel disease accompanied by axial spondyloarthritis
Yalong ZHU ; Si YU ; Jingyi HUANG ; Jinmei SU ; Qian WANG ; Yue LI
Chinese Journal of Inflammatory Bowel Diseases 2025;09(5):412-416
Objective:To summarize and analyze the clinical features of patients with inflammatory bowel disease (IBD) accompanied by axial spondyloarthritis (ax-SpA) .Methods:A descriptive case series study was conducted. Consecutive IBD patients with ax-SpA admitted to Peking Union Medical College Hospital from January 2012 to December 2023 were enrolled, and the clinical data were collected and analyzed descriptively.Results:A total of 21 IBD patients with ax-SpA were enrolled, including 14 males (66.7%) and 7 females (33.3%). The median age at IBD diagnosis was 29 (24, 42) years. Among them, 10 had ulcerative colitis (UC) and 11 had Crohn's disease (CD). In 11 patients (52.4%), ax-SpA was diagnosed before IBD, while in 7 patients (33.3%), IBD was diagnosed before ax-SpA; the remaining 3 patients (14.3%) were diagnosed simultaneously. Thirteen patients (61.9%) had other extraintestinal manifestations, with 12 involving mucocutaneous manifestations. Nineteen patients including 9 UC and 10 CD were followed up for a median duration of 34 (12, 57) months. Among UC patients, 5 (55.6%) were escalated from conventional therapy to biologics or small-molecule drugs, and 6 (66.7%) developed opportunistic infections. Among CD patients, 3 (30.0%) were escalated to biologic therapy, and 2 (20.0%) developed opportunistic infections. Three patients (15.8%) underwent intestinal resection surgery.Conclusions:IBD patients with ax-SpA are predominantly male, with a similar proportion of UC and CD. There is no clear sequential pattern in the diagnosis timing of IBD and ax-SpA. These patients often present with other extraintestinal manifestations of IBD, primarily mucocutaneous manifestations.
5.Management strategies for vesicovaginal fistula following cervical cancer radiotherapy in women
Jiemin SI ; Weidong ZHU ; Ranxing YANG ; Lujie SONG ; Chongrui JIN ; Jianwen HUANG ; Xuxiao YE ; Zuowei LI ; Wenxiong SONG ; Qiang FU ; Yinglong SA
Chinese Journal of Urology 2025;46(8):587-592
Objective:To investigate the treatment strategies for vesicovaginal fistula(VVF)in women following cervical cancer radiotherapy.Methods:A retrospective analysis was performed on the clinical data of 33 female patients with post-radiotherapy VVF after cervical cancer treatment at Shanghai Sixth People’s Hospital between January 2020 and June 2024. The patients were categorized into three groups based on surgical approaches:Group A(11 patients):Underwent prone-position VVF repair. Mean age:(50.0±9.6)years;mean radiotherapy sessions:(22.6±2.2). All had simple VVF without concurrent intestinal or surrounding soft-tissue fistulas. Among them,1 patient previously received laparoscopic VVF repair,1 transvaginal VVF repair,and 2 gracilis muscle flap packing for VVF repair. One month prior to surgery,the average daily usage of urine pads was 16.7(12.8,25.7)pieces,and the quality of life(QOL)score stood at 4.0(4.0,5.0)points. Preoperative cystoscopy revealed that 8 cases had fistulas located in the trigonal region of the bladder,while 3 cases had fistulas on the posterior bladder wall. The diameter of the fistula openings,measured under a microscope,was 1.2(0.8,1.6)cm. Based on the Goh classification criteria for vesicovaginal fistulas,this group included 3 cases of type 1,4 cases of type 2,2 cases of type 3,and 2 cases of type 4;7 cases of type A and 4 cases of type B;as well as 3 cases of typeⅠ,7 cases of type Ⅱ,and 1 case of type Ⅲ.Group B(20 patients):Underwent gracilis muscle flap packing for VVF repair. Mean age:(58.6±8.8)years;mean radiotherapy sessions:(29.8±3.9). Three patients had concurrent rectovaginal fistulas and received colostomy for fecal diversion. History of previous interventions:3 had laparoscopic VVF repair,4 transvaginal VVF repair,and 1 both transvaginal and laparoscopic VVF repair. One month prior to surgery,the average daily usage of urine pads was 19.7(15.8,27.7)pieces,and the QOL score stood at 5.0(5.0,6.0)points. Preoperative cystoscopy revealed that 13 cases had fistulas located in the trigonal region of the bladder,while 7 cases had fistulas on the posterior bladder wall. The diameter of the fistula openings,measured under a microscope,was 1.8(1.0,3.2)cm. Based on the Goh classification criteria for vesicovaginal fistulas,this group included 4 cases of type 1,9 cases of type 2,3 cases of type 3,and 4 cases of type 4;6 cases of type A,11 cases of type B and 3 cases of type C;as well as 1 cases of type Ⅱ,and 19 case of type Ⅲ. Group C(2 patients):Underwent ureterocutaneous diversion. Ages:67 and 73 years;radiotherapy sessions:51 and 60,respectively. Both had concurrent rectovaginal fistulas and bladder soft-tissue fistulas. The patient presented with recurrent thigh abscesses accompanied by fever. One month prior to surgery,the daily usage of urine pads was 29 and 23 pieces,respectively,and the QOL score was 6 points. Cystoscopic examination revealed that the vesicovaginal fistulas were located in the trigone of the bladder,with diameters of 3 cm and 4 cm,respectively. Additionally,partial defects were noted in the ventral wall of the urethra,while no bladder soft tissue fistulas were detected. According to the Goh classification for vesicovaginal fistulas,both cases were categorized as type 4,type C,and type Ⅲ. For Groups A and B,urinary catheters were indwelled for 3 weeks postoperatively,then removed to assess spontaneous urination and incontinence. QOL was evaluated,with a minimum 6-month follow-up. For confirmed postoperative VVF recurrence,re-repair was performed 3?6 months later based on patient preference. For Group C,double-J stents were placed in the ureters,and stoma bags were applied 3 days postoperatively. Stents were replaced every 1?2 months,with QOL assessment. Successful fistula repair in Groups A and B was defined as the absence of vaginal leakage confirmed by cystoscopy after six months of the procedure with no vaginal leakage. For Group C,surgical success was determined by the resolution of perineal urinary leakage and improvement in QOL.Results:All 33 patients completed surgery successfully. Group A:Follow-up duration:16.3(9.6,24.6)months. Surgical repair succeeded in 7 patients,with unobstructed spontaneous urination and no vaginal incontinence. Four patients had VVF recurrence:2 refused further treatment,and 2 underwent repeat gracilis muscle flap packing. One was successfully repaired,while one recurrence case refused further treatment. Group B:Follow-up duration:17.0(9.5,24.8)months(8?32 months). Thirteen patients restored spontaneous urination without recurrence. Seven had recurrence:5 refused further surgery,and 2 underwent re-repair. One repair succeeded without incontinence,while one recurrence case refused treatment. Group C:Follow-up durations were 6 and 22 months. Perineum remained dry without incontinence(no urine pads needed),and no recurrence of thigh soft-tissue redness/infection occurred. QOL scores were 2 and 3,respectively.Conclusions:Post-radiotherapy VVF in women after cervical cancer presents complex and variable conditions. The primary goal of treatment should be to improve patients’ quality of life. Treatment approaches should be selected based on the complexity of urinary fistulas and local tissue conditions. In general,patients who are younger,have received lower doses of radiation therapy,present with smaller fistula diameters,have well-vascularized and elastic perifistular tissues,and have no concurrent tissue fistulas are candidates for prone-position VVF repair. Patients who do not meet the criteria for transvaginal repair,have a history of at least two previous repair attempts,or have concurrent vaginorectal fistulas require gracilis muscle flap packing for VVF repair. Patients with three or more types of concurrent tissue fistulas,extensive pale and inelastic perifistular tissues,and who are not amenable to repair surgery undergo ureterocutaneous diversion.
6.Exon Sequencing of HNF1β in Chinese Patients with Early-Onset Diabetes
Siqian GONG ; Hong LIAN ; Yating LI ; Xiaoling CAI ; Wei LIU ; Yingying LUO ; Meng LI ; Si-min ZHANG ; Rui ZHANG ; Lingli ZHOU ; Yu ZHU ; Qian REN ; Xiuying ZHANG ; Jing CHEN ; Jing WU ; Xianghai ZHOU ; Xirui WANG ; Xueyao HAN ; Linong JI
Diabetes & Metabolism Journal 2025;49(2):321-330
Background:
Maturity-onset diabetes of the young (MODY) due to variants of hepatocyte nuclear factor 1-beta (HNF1β) (MODY5) has not been well studied in the Chinese population. This study aimed to estimate its prevalence and evaluate the application of a clinical screening method (Faguer score) in Chinese early-onset diabetes (EOD) patients.
Methods:
Among 679 EOD patients clinically diagnosed with type 2 diabetes mellitus (age at diagnosis ≤40 years), the exons of HNF1β were sequenced. Functional impact of rare variants was evaluated using a dual-luciferase reporter system. Faguer scores ≥8 prompted multiplex ligation-dependent probe amplification (MLPA) for large deletions. Pathogenicity of HNF1β variants was assessed following the American College of Medical Genetics and Genomics (ACMG) guidelines.
Results:
Two rare HNF1β missense mutations (E105K and G454R) were identified by sequencing in five patients, showing functional impact in vitro. Another patient was found to have a whole-gene deletion by MLPA in 22 patients with the Faguer score above 8. Following ACMG guidelines, six patients carrying pathogenic or likely pathogenic variant were diagnosed with MODY5. The estimated prevalence of MODY5 in Chinese EOD patients was approximately 0.9% or higher.
Conclusion
MODY5 is not uncommon in China. The Faguer score is helpful in deciding whether to perform MLPA analysis on patients with negative sequencing results.
7.Correlation between serum zinc level and prognosis of patients with sepsis
Xiao-Gang WANG ; Jia-Jun MA ; Rui-Xin ZHU ; Li-Bing ZHOU ; Sai-Hu HUANG ; Shui-Yan WU ; Wen-Si NIU ; Jie HUANG ; Zhen-Jiang BAI
Parenteral & Enteral Nutrition 2025;32(5):278-282
Objective:To investigate the differences in clinical outcomes of septic children with varying serum zinc levels,and to analyze the relationship between reduced serum zinc levels and organ dysfunction as well as 28-day mortality in septic children.Methods:This study conducted a retrospective analysis of clinical data from pediatric patients diagnosed with sepsis or septic shock in the Department of critical care medicine of the children's Hospital of Soochow University between January 2017 and December 2022.Clinical characteristics,organ dysfunction,and prognosis were compared between two groups:children with low serum zinc levels and those with normal zinc levels.Results:The serum zinc level of septic children within 24 hours of admission was 9.60(5.52,13.80)μmol/L,with 50.54%(94/186)of the children exhibiting low serum zinc levels(<10.07 μmol/L).Compared to the normal serum zinc group,the low serum zinc group had a significantly lower Pediatric Critical Illness Score(PCIS)[(78.71±9.35)vs.(85.12±8.51),P=0.005]and higher 28-day mortality(46.80%vs.14.13%,P<0.001).The low serum zinc group also had a higher proportion of invasive mechanical ventilation(64.89%vs.47.82%,P=0.019),renal replacement therapy(15.59%vs.3.26%,P=0.003),and use of vasoactive drugs(56.38%vs.30.43%,P<0.001).The rate of underlying conditions in the low serum zinc group was significantly higher than that in the normal serum zinc group(57.44%vs.36.95%,P=0.005).Additionally,the low serum zinc group had a higher incidence of disseminated intravascular coagulation(DIC),respiratory failure,acute kidney injury,shock,and multiple organ dysfunction syndrome(MODS)compared to the normal serum zinc group(P<0.05).Serum zinc levels had predictive value for 28-day mortality in septic children(AUC=0.813;95%CI:0.725~0.902;P<0.001).A serum zinc level of less than 6.950 μmol/L predicted the death of septic children with a sensitivity of 0.618 and a specificity of 0.902.Conclusion:Sepsis in children is commonly associated with low serum zinc levels,especially in those with underlying conditions such as hematologic and oncologic disorders.Sepsis patients hypozincemia with a higher incidence of DIC,respiratory failure,acute kidney injury,shock,and MODS.A serum zinc level below 6.95 μmol/L serves as a significant predictor of 28-day mortality in children with severe sepsis.
8.Determination of Lipid Components in Fingerprints by Gas Chromatography-Mass Spectrometry and Gender Recognition of Fingerprint Donors by Machine Learning
Zi-Chen YI ; Wen-Ji ZHANG ; Zi-Yong ZHU ; Wei YI ; Jia-Si JIANG ; Zi-Hua LI
Chinese Journal of Analytical Chemistry 2025;53(8):1290-1299,中插19-中插22
Gender recognition based on the analysis of fingerprint residue can assist investigators in narrowing down the scope of investigation and play an important role in the field of criminal investigation.This study established a quantitative analysis method for lipid substances in fingerprints based on gas chromatography-mass spectrometry(GC-MS).Fatty acids in fingerprints were methylated using sulfuric acid methanol derivatization reagent(7%,V/V),the extraction reagent was dichloromethane-methanol(1∶1,V/V)solution,the reaction temperature was 70℃and the heating time was 45 min.Quantitative analysis of the relative content of 23 kinds of fatty acids and squalene in fingerprints residue by different genders was conducted,and orthogonal partial least squares-discriminant analysis(OPLS-DA)was used to reduce the dimensionality of the quantitative results.A total of 13 kinds of components in the fingerprints were selected to maximize the difference in relative content between male and female fingerprints.Three machine learning models,including binary logistic regression(BLR),support vector machine(SVM)and random forest(RF),were further used as feature variables to classify the gender of fingerprints.The classification performance of each model was compared through five indicators,and it was found that the most suitable model for binary classification of fingerprint gender was SVM model.The results showed that the SVM fingerprint residual gender binary classification model established based on the relative content data of 13 kinds of lipid substances in fingerprints achieved a classification accuracy of 90%and an area under the receiver operating characteristic curve(AUC)value of 0.98.This study provided a new research method for detecting lipid components in fingerprints and a methodological basis for gender recognition of fingerprints.
9.Mechanotransduction proteins in intervertebral disc degeneration
Xilin GAO ; Si WU ; Chao ZHANG ; Liguo ZHU ; Bifeng FU ; Ping WANG
Chinese Journal of Tissue Engineering Research 2025;29(3):579-589
BACKGROUND:Recent research indicates that disc degeneration is closely related to abnormal stress load,and mechanotransduction proteins play a key role in it. OBJECTIVE:To investigate the role and mechanism of mechanotransduction proteins in the mechanotransduction process induced by abnormal mechanical stimulation in disc degeneration,and to summarize the current treatment strategies targeting mechanotransduction to delay intervertebral disc degeneration. METHODS:Using"intervertebral disc,nucleus pulposus,annulus fibrosus,cartilaginous endplate,cell,mechanics,signal transduction,protein,biomechanics"as Chinese search terms,and"intervertebral disc,nucleus pulposus,annulus fibrosus,cartilaginous endplate,cell,mechanical stimulation,signal transduction,protein,biomechanics"as English search terms,relevant literature in the PubMed and CNKI databases was searched.A total of 88 articles were ultimately included for review. RESULTS AND CONCLUSION:Disc cells can sense external mechanical stimulation through various mechanotransduction proteins and convert it into biological responses within the cells.These transduction proteins mainly include collagen proteins in the extracellular matrix,cell membrane surface receptors(such as integrins and ion channels),and cytoskeleton structural proteins.Their regulation of mechanotransduction processes primarily involves the activation of multiple pathways,such as the PI3K/AKT signaling pathway,nuclear factor-kB signaling pathway,and Ca2+/Calpain2/Caspase3 pathway.Mechanotransduction proteins play a key role in the mechanotransduction of disc cells.Abnormal expression of these proteins or resulting changes in the extracellular matrix environment can disrupt the mechanical balance of disc cells,leading to disc degeneration.In-depth study of the expression and regulatory mechanisms of mechanotransduction proteins in disc cells,and identification of key pathological links and therapeutic targets,is of significant importance for developing treatment strategies for disc degeneration.Current strategies to delay intervertebral disc degeneration by targeting mechanotransduction mainly include regulation of transduction proteins and improvement of the extracellular matrix.However,research in this area is still in its early stages.As research continues,new breakthroughs are expected in the regulation of disc degeneration by mechanotransduction proteins.
10.Mining and verification of inflammation-related genes in skeletal muscle of exhaustive exercise rats undergoing cannabidiol intervention
Wenning ZHU ; Lili SUN ; Lina PENG ; Juncheng SI ; Wanli ZANG ; Weidong YIN ; Mengqi LI
Chinese Journal of Tissue Engineering Research 2025;29(11):2347-2356
BACKGROUND:Cannabidiol is effective in ameliorating the body's inflammatory response,but no clear mechanistic studies have been conducted to ameliorate skeletal muscle inflammation induced by exhaustive exercise. OBJECTIVE:To explore the mechanism by which cannabidiol improves skeletal muscle inflammation during exhaustive exercise by using transcriptome sequencing technology. METHODS:Thirty-six Sprague-Dawley rats were randomly divided into six groups:blank control group,exercise coconut oil group,exercise control group,50 mg/kg cannabidiol group,60 mg/kg cannabidiol group,and 70 mg/kg cannabidiol group,with six rats in each group.Except for rats in the blank control group,rats in each group were subjected to swimming exercise for 9 days to produce the exhaustive exercise model.At the end of each swimming exercise,rats in the cannabidiol groups were given 2 mL of fat-soluble cannabidiol at different concentrations(50,60,and 70 mg/kg)by gavage;rats in the exercise coconut oil group were given the same volume of coconut oil by gavage until the end of the exercise on the 9th day;and rats in the blank control group and the exercise control group were not given any special treatment.The levels of inflammatory factors and differentially expressed genes in the skeletal muscle of rats in each group were determined using ELISA and transcriptome sequencing techniques.Differentially expressed genes obtained were subjected to KEGG analysis,and the accuracy of the sequencing data was verified by fluorescence quantitative PCR. RESULTS AND CONCLUSION:The results of ELISA showed that the contents of interleukin-6(P<0.05),tumor necrosis factor-α(P<0.01),interleukin-10 and other inflammatory factors in the exercise group increased significantly compared with the blank control group and the coconut oil group.After cannabidiol intervention,the mass concentrations of interleukin-6 and tumor necrosis factor-α showed a sequential decrease with increasing cannabidiol concentration.By comparing GO and KEGG databases,the functional properties of differentially expressed genes were analyzed,and the results showed that the differentially expressed genes were mainly involved in the tumor necrosis factor signaling pathway and the Toll-like receptor signaling pathway.RT-qPCR results showed that the trends of five randomly selected differentially expressed genes were in agreement with the transcriptome sequencing results.To conclude,cannabidiol can improve skeletal muscle inflammation caused by exhaustive exercise.


Result Analysis
Print
Save
E-mail