Purpose To explore the clinicopathologic features and differential diagnosis of nephrogenic adenomas(NAs)in urinary tract.Methods 27 cases of NA were collected.The clinicopathological features and differential di-agnosis were analyzed,and the relevant literatures were reviewed.Results A total of 27 cases of NA in urinary tract were included in this study,including 20 males and 7 females,ranging in age from 24 to 84 years.Among them,clini-cal manifestations included urinary tract irritation in 8 cases,hematuria in 7 cases,and no obvious symptoms or other comorbidities in 12 cases.Comorbidities:17 cases combined with urothelial tumors,4 cases with cystitis,2 cases with tuberculosis,2 cases with urethral diverticulum,and 2 cases with ureteral calculi or stenosis.Gross inspection:19 ca-ses occurred in the bladder,5 in the ureter,and 3 in the urethra.The average size of the lesions was about 4.3 mm.Local edema or protrusion of the mucosa with roughness were found in 18 cases,papillary or polypoid masses in 5 ca-ses,or follicular-like neoplasma in 4 cases.Histologic features:these lesions were mainly composed of papillary,tubu-lar and cystic structure,and eosinophilic colloid secretions were seen in the lumen.The lining epithelium was cuboidal or low columnar,some of which were 'hobnail' or signet ring-like cells,and stroma showed edema and chronic inflam-mation.Immunohistochemistry:epithelial cells expressed PAX8 and CK7,partially expressed P504S and GAT A3,but not p63 and PSA.p53 was wild type,and Ki67 proliferation index was low(1％-8％).Molecular testing:no ab-normalities were found in 14 urine FISH tests before surgery,and no fusion mutation was detected in 2 samples selected for second-generation sequencing.Treatment and follow-up:follow-up data were obtained for all cases,of which 24 un-derwent transurethral resection of bladder lesions,and the rest underwent nephroureterectomy or cystoprostatectomy.The mean follow-up was 26.6(1-59)months,and the lesion recurred in 2 cases.Conclusion NAs are relatively rare,and their final diagnosis depends on pathological examination.When the biopsy sample is small or the histomor-phology is atypical,it's often necessary to differentiate it from urothelial tumor,prostate adenocarcinoma and clear cell adenocarcinoma.Understanding the clinicopathologic and immunohistochemical features of NA is helpful to improve the diagnostic rate and avoid missed-diagnosis or misdiagnosis.

Purpose To explore the clinicopathologic features and differential diagnosis of nephrogenic adenomas(NAs)in urinary tract.Methods 27 cases of NA were collected.The clinicopathological features and differential di-agnosis were analyzed,and the relevant literatures were reviewed.Results A total of 27 cases of NA in urinary tract were included in this study,including 20 males and 7 females,ranging in age from 24 to 84 years.Among them,clini-cal manifestations included urinary tract irritation in 8 cases,hematuria in 7 cases,and no obvious symptoms or other comorbidities in 12 cases.Comorbidities:17 cases combined with urothelial tumors,4 cases with cystitis,2 cases with tuberculosis,2 cases with urethral diverticulum,and 2 cases with ureteral calculi or stenosis.Gross inspection:19 ca-ses occurred in the bladder,5 in the ureter,and 3 in the urethra.The average size of the lesions was about 4.3 mm.Local edema or protrusion of the mucosa with roughness were found in 18 cases,papillary or polypoid masses in 5 ca-ses,or follicular-like neoplasma in 4 cases.Histologic features:these lesions were mainly composed of papillary,tubu-lar and cystic structure,and eosinophilic colloid secretions were seen in the lumen.The lining epithelium was cuboidal or low columnar,some of which were 'hobnail' or signet ring-like cells,and stroma showed edema and chronic inflam-mation.Immunohistochemistry:epithelial cells expressed PAX8 and CK7,partially expressed P504S and GAT A3,but not p63 and PSA.p53 was wild type,and Ki67 proliferation index was low(1％-8％).Molecular testing:no ab-normalities were found in 14 urine FISH tests before surgery,and no fusion mutation was detected in 2 samples selected for second-generation sequencing.Treatment and follow-up:follow-up data were obtained for all cases,of which 24 un-derwent transurethral resection of bladder lesions,and the rest underwent nephroureterectomy or cystoprostatectomy.The mean follow-up was 26.6(1-59)months,and the lesion recurred in 2 cases.Conclusion NAs are relatively rare,and their final diagnosis depends on pathological examination.When the biopsy sample is small or the histomor-phology is atypical,it's often necessary to differentiate it from urothelial tumor,prostate adenocarcinoma and clear cell adenocarcinoma.Understanding the clinicopathologic and immunohistochemical features of NA is helpful to improve the diagnostic rate and avoid missed-diagnosis or misdiagnosis.

Objective·To explore EDAR(ectodysplasin A receptor)gene variants that lead to congenital tooth agenesis,and preliminarily analyze the reasons why variants in EDAR can cause both syndromic and non-syndromic tooth agenesis.Methods·Patients with congenital tooth agenesis admitted to the Department of 2nd Dental Center,Shanghai Ninth People's Hospital,Shanghai Jiao Tong University School of Medicine and their family members were included,and genomic DNA from their peripheral blood was extracted for whole exome sequencing(WES).After preliminary screening,PolyPhen-2,Mutation Taster,and Provean were used to predict the harmfulness of potential variants.The screened variants in patients and their families were verified by Sanger sequencing.Conservation analysis of variants was performed,and Swiss-Model was used to analyze the changes in the three-dimensional structure of EDAR.The teeth and syndromic phenotype of the patients and their family members were investigated.Results·Among the included congenital tooth agenesis patients,five patients with EDAR mutations were found,one with EDAR frameshift mutation c.368_369insC(p.L123fs)and the other four with EDAR missense mutations.Two of these four patients were diagnosed as non-syndromic tooth agenesis(NSTA),resulted from c.77C＞A(p.A26E)homozygous mutation and c.380C＞T(p.P127L)heterozygous mutation,respectively.The other two patients with two variants were diagnosed as hypohidrotic ectodermal dysplasia(HED).One compound heterozygous missense mutation patient carried EDAR c.77C＞T(p.A26V)from her father andEDAR c.1281G＞C(p.L427F)from her mother;the other patient with both EDAR and EDA mutations carried EDAR c.1138A＞C(p.S380R)heterozygous mutation and EDA c.1013C＞T(p.T338M)hemizygous mutation.Both variants were from his mother and were reported to be related with NSTA.Two of these missense mutations,EDAR c.1281G＞C(p.L427F)and EDAR c.77C＞A(p.A26E),had not been reported before.The missense mutations affected the protein's spatial conformation by altering the polarity,charge,or volume of the amino acid residues.The frameshift mutation caused a non-triplet base addition,which probably led to protein truncation or degradation.Conclusion·Two new EDAR missense mutations are discovered.An NSTA patients with EDAR homozygous mutations and an HED patient with both EDA and EDAR mutations are reported.It expands the understanding of pathogenic mechanisms of EDAR mutations causing HED and NSTA.

Artificial neural network(ANN)is a simulation of a biological neural network.It is an adaptive,non-linear,dynamic network system formed by interconnections.The advantages of ANN include easy optimization,simple modeling,and ac-curate results.This review examines the application of ANN in therapeutic drug monitoring for immunosuppressants,antibacteri-als,and anti-epileptic drugs.It discusses the advantages and disadvantages of the current ANN models and highlights future de-velopment directions.The aim is to provide valuable reference information for future researchers.The use of ANN for therapeutic drug monitoring shows great potential and holds promise as an effective method of personalizing patient medication.

Objective To imporve the service level of integrated outpatient department for cardio-oncology in healthcare facilities,and to improve and optimize pharmaceutical management within cardio-oncology integrated outpatient department.Methods Clinical issues were identified using the Delphi method.Relevant problems and existing evidence were collected and organized through systematic research.The evidence grading and recommendation intensity standards developed by the Center for Evidence-Based Medicine at Oxford University were applied to complete the evidence grading.Through questionnaire consultations with 38 experts.Results A total of 11 clinical questions were identified as consensus items.Based on these issues,expert consensus recommendations for pharmaceutical management in combined cardio-oncology outpatient departments were formulated through evidence retrieval,synthesis,and grading.Ultimately,an expert consensus on pharmaceutical management in combined cardio-oncology outpatient clinics was established.Conclusion The expert consensus serves as a reference for managing combined clinical cardio-oncology outpatient clinics,significantly contributing to offering more professional and comprehensive diagnosis and treatment services for cancer patients.

Objective:This study aims to explore the prevalence of hepatitis E virus (HEV) infection in patients and the screening value of serological indicators for HEV infection patients.Methods:Retrospective analysis was conducted on 97 440 cases of anti-HEV IgM and IgG simultaneously tested in two Beijing hospitals from January 1, 2018 to August 31, 2023. Among them, there were 61 005 males and 36 435 females, with an average age of 51.65±13.05 years old. According to the positivity of anti HEV specific antibodies, they were divided into anti-HEV IgM positive group (3 588 cases), anti-HEV IgG positive group (18 083 cases), and anti-HEV antibody negative group (78 892 cases). Results of HEV RNA, liver function, AFP, PIVKA-Ⅱ and PT were collected, and their basic clinical information were recorded. The prevalence of HEV infection in patients, as well as the relationship between the positivity of anti-HEV specific antibodies and the patient′s age group, HEV RNA, and clinical characteristics were analyzed.Results:Among 97 440 patients who tested anti-HEV IgM and IgG simultaneously, the positivity rate of anti-HEV IgM was 3.68% (3 588/97 440), and was 18.56% for anti-HEV IgG (18 083/97 440). The overall positivity rates of anti-HEV IgM in two Beijing hospitals from 2018 to 2023 were 2.51%, 2.53%, 3.02%, 4.59%, 5.72%, and 4.26% ( χ2=1 401.73, P<0.001), while the positivity rates of anti-HEV IgG were 12.56%, 12.32%, 12.85%, 22.65%, 27.42%, and 26.66% ( χ2=1 058.29, P<0.001). These rates showed a gradual increase until 2023 when a decline was observed. The positivity rates of anti-HEV IgM (2.28%, 3.60%, 4.47%) ( χ2=89.62, P<0.001) and IgG (4.71%, 17.86%, 25.94%) ( χ2=2 017.32, P<0.001) increased with age in patients who aged 1-30, >30-60, and over 60 years old. The age and ALB values of patients in the anti-HEV IgM positive group were lower than the IgG-positive group, while the proportion of males, TBIL, ALT, AFP and PT values were higher than the IgG-positive group, and the differences were statistically significance ( P<0.05). Furthermore, patients in both the anti-HEV IgM and IgG positive groups had higher age, male proportion, TBIL, ALT, AFP, PIVKA-Ⅱ, and PT values than the anti-HEV negative group. Additionally, both groups had lower ALB values than the anti-HEV negative group, all of which were statistically significant ( P<0.05). 2 162 HEV infected patients were grouped based on HEV RNA positivity. The proportion of anti-HEV IgM single positive, IgG single positive, IgM+IgG double positive, and antibody negative patients in the HEV RNA positive group were 5.42% (18/332), 3.62% (12/332), 90.36% (300/332), and 0.60% (2/332), respectively. Among them, the proportion of anti-HEV IgM+IgG double positive patients in the HEV RNA positive group was higher than that in the HEV RNA negative group ( χ2=302.87, P<0.001), while the proportion of anti-HEV IgG single positive ( χ2=174.36, P<0.001) and anti-HEV antibody negative patients ( χ2=59.28, P<0.001) were lower than that in the HEV RNA negative group, both of which were statistically significant ( P<0.001). In addition, the positive rates of HEV RNA in anti-HEV IgM positive, IgG positive, and antibody negative patients were 29.23% (318/1 088), 17.59% (312/1 774), and 0.65% (2/306), respectively. Conclusion:The HEV infection rate among patients declined in 2023. HEV infection is age-related, with older individuals being more susceptible. Abnormal liver function and jaundice were commonly observed during HEV infection. It is crucial to note that the absence of anti-HEV specific antibodies cannot rule out HEV infection; therefore, additional testing for HEV RNA and/or HEV Ag is necessary for accurate diagnosis.

Helicobacter pylori （Hp）， a spiral-shaped microaerophilic Gram-negative bacterium that has been classified as a class Ⅰ carcinogen by the World Health Organization， is associated with a variety of digestive system diseases. With the popularization of antibiotic therapy， Hp resistance has become the main reason for the failure of the eradication treatment of Hp. A variety of Chinese medicines have been proved to have anti-Hp effects， which are expected to serve as new options for the eradication of Hp. By reviewing the recent literature in China and abroad， we summarized the understanding of Chinese medicines in the treatment of Hp infection and elaborated on the mechanisms from two aspects： direct killing and indirect inhibition. On the one hand， Chinese medicines can directly kill Hp by inhibiting the growth， respiration， and metabolism of Hp， destroying the morphological structure of Hp， and inhibiting the formation of Hp biofilm. On the other hand， Chinese medicines can inhibit Hp by reducing Hp adhesion and colonization， regulating Hp-caused immune response， inhibiting Hp-caused inflammation， and alleviating the Hp-caused oxidative stress and gastric mucosal injury. Specifically， the indirect inhibition of Hp can be achieved via the following ways. Chinese medicines can reduce Hp adhesion and colonization by reducing Hp motility， inhibiting urease activity and the expression of related genes， and decreasing the production of adhesion proteins. They can regulate the Hp-caused immune responses by enhancing the immune protective response， modulating lysosomal function and immune cytokines， avoiding the immune evasion of Hp， and maintaining the balance between immunity and inflammation. Chinese medicines can inhibit Hp-caused inflammatory responses by inhibiting the release of inflammatory cytokines， down-regulating the expression of virulence factors， and regulating the targets and signaling pathways in the treatment of inflammation. In addition， Chinese medicines can alleviate the Hp-caused oxidative stress and gastric mucosal injury by improving the activities of antioxidant enzymes and oxidases， regulating the generation of reactive oxygen species and reactive nitrogen， and inhibiting inflammatory mediators. This article systematically introduces the mechanisms of Chinese medicines against Hp， aiming to provide a theoretical and scientific basis for the research and clinical application of Chinese medicines against Hp.

Objective:To explore the clinical significance of hepatitis B virus (HBV) DNA detection in screening patients with hepatitis B.Methods:Clinical data of 682 331 hepatitis B patients were retrospectively analyzed. The HBV DNA of these patients was detected in the Fifth Medical Center of the PLA General Hospital from January 2017 to December 2021, there were 481 159 males and 201 172 females in this cohort, the average age was (41.34±16.13) years. Patients were divided into HBV DNA positive group (219 879 cases) and HBV DNA negative group (462 452 cases). Clinical characteristics, data of five serologic markers of hepatitis B and hepatitis B surface antigen quantification (HBsAg-QN), liver function, alpha fetoprotein (AFP) and prothrombin time (PT) results were collected and analyzed and compared between the two groups.Results:The positive rate of HBV DNA was 32.22% (219 879/682 331) in this cohort. Among the different age groups, the positive rate of HBV DNA was the highest (40.34%, 128 038/317 380) in young people aged 18-44 years. The proportion of patients was lower among aged <1, 45-59 and ≥60 years patients in HBV DNA positive group than that in HBV DNA negative group, while the proportion of patients was higher among aged 1-17 and 18-44 years patients in HBV DNA positive group than that in HBV DNA negative group (all P<0.001). Among 2 291 <1-year-old infants tested for HBV DNA, 71 infants were HBV DNA positive. The positive rates of HBV DNA from 2017 to 2021 were 4.86% (27/556), 3.68% (14/380), 3.47% (17/490), 1.55% (6/386) and 1.46% (7/479) respectively, showing a downward trend year by year. The positive rate of HBV DNA in acute hepatitis B (AHB) patients was the highest (49.88%, 208/417) among 680 040 patients with hepatitis B. The proportion of AHB patients (0.09%, 208/219 808) and chronic hepatitis B (80.44%, 176 806/219 808) in HBV DNA positive group was higher than that in HBV DNA negative group [0.05% (209/460 232) and 65.45% (301, 216/460 232)], while the proportion of patients with HBV-related liver cirrhosis (11.28%, 24 793/219 808), HBV-related liver cancer (6.72%, 14 775/219 808), liver cancer surgery (1.39%, 3 055/219 808) and liver transplantation (0.08%, 171/219 808) were lower than that in HBV DNA negative group [22.99% (105 813/460 232), 7.25% (33 385/460 232), 3.50% (16 129/460 232) and 0.76% (3 480/460 232)] (all P<0.001). At the same time, positive rate of hepatitis B surface antigen (HbsAg), HBsAg-QN, hepatitis B e antigen (HbeAg), level of total bilirubin, total bilirubin, AFP and PT were higher in HBV DNA positive group than those in HBV DNA negative group, while the age, male ratio and albumin results in HBV DNA positive group were lower than those in HBV DNA negative group (all P<0.01). The HBV DNA loads were higher in HBsAg positive group, hepatitis B surface antibody positive group and HBeAg positive group than those in respective negative groups, while the HBV DNA loads were lower in hepatitis B e antibody positive group and hepatitis B core antibody positive group than those in respective negative groups (all P<0.001). Conclusions:The mother to child transmission rate of<1-year-old infants decreases year by year. HBV DNA is an important factor for the progression of hepatitis B disease. HBV DNA positive hepatitis B patients with higher HBsAg-QN values are more likely to have abnormal serum markers such as liver dysfunction. HBV DNA detection is therefore of clinical importance in screening patients with hepatitis B.

Objective:To investigate the correlation between 25 hydroxyvitamin D[25 (OH) D] level and sleep monitoring index in patients with severe altitude obstructive sleep apnea hypopnea syndrome (OSAHS).Methods:Sixty-six patients with severe OSAHS (AHI≥30 times/hour) diagnosed by apnea hypopnea index (AHI) who had lived at high altitude (1 800-4 193 m) for≥1 year were included in the experimental group. The patients underwent polysomnography monitoring in Sleep Medicine Center of Qinghai Red Cross Hospital from June to December 2021. In addition, healthy volunteers matched the experimental group by gender, age, ethnicity and living altitude during the same period were selected for polysomnography monitoring. Finally, 48 healthy volunteers with AHI<5 times/hour were included as the control group. 25(OH)D level and its deficiency were compared between the two groups. The experimental group was further divided into severe deficiency group [25(OH)D≤10 μg/L], the deficiency group [10 μg/L<25(OH)D≤20 μg/L] and the non-deficiency group [25(OH)D>20 μg/L] according to 25(OH)D level, and the differences of sleep parameters among the three groups were compared. Correlation analysis and multifactor linear regression analysis were performed on the factors that may affect the level of 25(OH)D in patients with severe OSAHS.Results:A total of 114 adults living on the plateau for at least one year were enrolled, including 66 in the experimental group and 48 in the control group. 25(OH)D deficiency (≤30 μg/L) was found in all the individuals included in the experimental group and the control group, and the 25(OH)D level of the two groups was [(13.13±4.05) vs (13.68±4.60) μg/L, P=0.507] and there was no significant difference in deficiency degree (all P>0.05). Within the experimental group, rapid eye movement (REM) sleep time and proportion (REM%) and sleep awakening time of 25(OH)D non-deficiency group, were significantly lower than those in severe deficiency group (all P<0.05), and sleep efficiency in 25(OH)D non-deficiency group was significantly higher than that in severe deficiency group and deficiency group (all P<0.05). Spearman correlation analysis showed that the level of 25 (OH) D in experimental group were positively correlated with serum calcium ion level ( r=0.293, P=0.017) and sleep efficiency ( r=0.309, P=0.011), and were negatively correlated with age ( r=-0.298, P=0.015), REM sleep time ( r=-0.401, P=0.001), REM% ( r=-0.421, P<0.001) and awakening time ( r=-0.362, P=0.003). Multifactor linear regression analysis suggested that serum calcium, REM sleep time and history of hypertension were the predictors of 25(OH)D level in severe OSAHS at high altitude. Conclusions:There is a correlation between sleep monitoring indexes and serum 25(OH)D level in patients with severe OSAHS at high altitude. The longer the REM sleep time, the lower the 25(OH)D level. Meanwhile, there is a certain relationship between co-morbidity hypertension and 25(OH)D level in patients with severe OSAHS at high altitude.

Objective:In this article, we analyzed and discussed the clinical characteristics and S region gene sequencing of hepatitis B virus in HBsAg anti-HBs coexistent patients.Methods:Data of 5 serologic markers of hepatitis B and quantitative result, liver function and HBV DNA load of HBsAg positive patients were collected, and their basic clinical information were recorded. According to the positive and negative result of Anti-HBs, the clinical and virological characteristics of these two groups were analyzed. At the same time, among 17 320 patients with HBsAg positive HBV infection, 994 cases were tested by gene sequencing. The S region amino acid mutation, site mutation detection rate and genotype of 994 HBV infected patients with gene sequencing were statistically analyzed.Results:The positive rate of HBsAg and Anti-HBs was 4.36% (756/17 320). HBV-related cirrhosis in HBsAg+ /Anti-HBs+ group (19.71%) was significantly higher than that in HBsAg+ /Anti-HBs-group (15.94%), while chronic hepatitis B (62.04%) was significantly lower than that in HBsAg+ /Anti-HBs-group (67.06%). At the same time, the positive rates of HBsAg-quantification (QN) and ALT in HBsAg+ /Anti-HBs+ group were significantly lower than those in HBsAg+ /Anti-HBs-group, the positive rate of HBeAg was significantly higher than that in HBsAg+ /Anti-HBs-group, and the HBV DNA was higher than that in HBsAg+ /Anti-HBs-group, but the difference was no statistical significance. Gene sequencing was performed in 994 HBV patients. Genotype C (81.79%) had the highest proportion, genotype B (17.40%) was the second, and genotype D (0.80%) was the least in two groups. In genotype C HBV infected patients, the detection rate of sP120Q/T/A/S mutant in HBsAg+ /Anti-HBs+ group was significantly higher than that in HBsAg+ /Anti-HBs-group. Meanwhile, regardless of genotype B or C or overall comparison, the detection rate of sG145A/E/K/R mutant of HBV infected patients in HBsAg+ /Anti-HBs+ group was significantly higher than that in HBsAg+ /Anti-HBs-group, these differences were all statistically significant.Conclusions:The hepatitis B patients with coexistence of HBsAg and Anti-HBs were more likely to develop cirrhosis, and the hepatitis B patients with HBV gene sequencing results were mainly type C2. The drug resistance variation of S-region sP120Q/T/A/S and sG145A/E/K/R mutants of patients with HBV infection is an important reason for the coexistence of HBsAg and Anti-HBS.