Objectives:To evaluate the clinical value of the Paris system for reporting urinary cytology (TPS) in the diagnosis of urothelial carcinoma (UC).Methods:A total of 1 744 cytological diagnostic records (from 751 cases) were collected retrospectively. All specimens were voided urines and histopathology as the gold standard. The sensitivity and specificity of urinary cytological diagnosis of UC and risk of high grade malignant (ROHM) in each diagnostic category were compared.Results:There were 360 cases with histopathology. The percentage of negative for high-grade urothelial carcinoma (NHGUC) was 30.1% (226/751), atypical urothelial cells (AUC) was 29.8% (224/751), suspicious for high-grade urothelial carcinoma (SHGUC) was 16.8% (126/751), high grade urothelial carcinoma (HGUC) was 21.2% (159/751), and non-urothelial malignancy (NUM) was 2.1% (16/751). The histpathologic ROHM corresponding to each cytological diagnosis category were 27.3% for NHGUC, 32.7% for AUC, 74.7% for SHGUC, 96.6% for HGUC and 100.0% for NUM, respectively. ROHM of SHGUC was significantly higher than that of AUC group, and the difference between the two groups was statistically significant ( P＜0.001). ROHM of HGUC group was significantly higher than that of SHGUC group, and the difference was statistically significant ( P＜0.001). With SHGUC as the cut-off value, the sensitivity and specificity of cytological diagnosis of HGUC were 76.7% (165/215) and 85.7% (18/21), and with HGUC as the cut-off value, the sensitivity and specificity of cytological diagnosis of HGUC were 53.0% (114/215) and 100.0% (21/21), respectively. Conclusions:Urine cytology has high sensitivity and specificity in the diagnosis of HGUC. The malignant risk of TPS varies with different diagnosis category. The high malignant risk population in cancer hospital leads to the relatively high malignant proportion and ROHM in each diagnosis category. Urinary cytology TPS reporting system is helpful to clinical management and has good clinical application value.

Objectives:To evaluate the clinical value of the Paris system for reporting urinary cytology (TPS) in the diagnosis of urothelial carcinoma (UC).Methods:A total of 1 744 cytological diagnostic records (from 751 cases) were collected retrospectively. All specimens were voided urines and histopathology as the gold standard. The sensitivity and specificity of urinary cytological diagnosis of UC and risk of high grade malignant (ROHM) in each diagnostic category were compared.Results:There were 360 cases with histopathology. The percentage of negative for high-grade urothelial carcinoma (NHGUC) was 30.1% (226/751), atypical urothelial cells (AUC) was 29.8% (224/751), suspicious for high-grade urothelial carcinoma (SHGUC) was 16.8% (126/751), high grade urothelial carcinoma (HGUC) was 21.2% (159/751), and non-urothelial malignancy (NUM) was 2.1% (16/751). The histpathologic ROHM corresponding to each cytological diagnosis category were 27.3% for NHGUC, 32.7% for AUC, 74.7% for SHGUC, 96.6% for HGUC and 100.0% for NUM, respectively. ROHM of SHGUC was significantly higher than that of AUC group, and the difference between the two groups was statistically significant ( P＜0.001). ROHM of HGUC group was significantly higher than that of SHGUC group, and the difference was statistically significant ( P＜0.001). With SHGUC as the cut-off value, the sensitivity and specificity of cytological diagnosis of HGUC were 76.7% (165/215) and 85.7% (18/21), and with HGUC as the cut-off value, the sensitivity and specificity of cytological diagnosis of HGUC were 53.0% (114/215) and 100.0% (21/21), respectively. Conclusions:Urine cytology has high sensitivity and specificity in the diagnosis of HGUC. The malignant risk of TPS varies with different diagnosis category. The high malignant risk population in cancer hospital leads to the relatively high malignant proportion and ROHM in each diagnosis category. Urinary cytology TPS reporting system is helpful to clinical management and has good clinical application value.

Objective: To analyze the clinical and molecular diagnostic status of Fanconi anemia (FA) in China. Methods: The General situation, clinical manifestations and chromosome breakage test and genetic test results of 107 pediatric FA cases registered in the Chinese Blood and Marrow Transplantation Registry Group (CBMTRG) and the Chinese Children Blood and Marrow Transplantation Registry Group (CCBMTRG) from August 2009 to January 2022 were analyzed retrospectively. Children with FANCA gene variants were divided into mild and severe groups based on the type of variant, and Wilcoxon-test was used to compare the phenotypic differences between groups. Results: Of the 176 registered FA patients, 69 (39.2%) cases were excluded due to lack of definitive genetic diagnosis results, and the remaining 107 children from 15 hospitals were included in the study, including 70 males and 37 females. The age at transplantation treatment were 6 (4, 9) years. The enrolled children were involved in 10 pathogenic genes, including 89 cases of FANCA gene, 7 cases of FANCG gene, 3 cases of FANCB gene, 2 cases of FANCE gene and 1 case each of FANCC, FANCD1, FANCD2, FANCF, FANCJ, and FANCN gene. Compound heterozygous or homozygous of loss-of-function variants account for 69.2% (72/104). Loss-of-function variants account for 79.2% (141/178) in FANCA gene variants, and 20.8% (37/178) were large exon deletions. Fifty-five children (51.4%) had chromosome breakage test records, with a positive rate of 81.8% (45/55). There were 172 congenital malformations in 80 children.Café-au-Lait spots (16.3%, 28/172), thumb deformities (16.3%,28/172), polydactyly (13.9%, 24/172), and short stature (12.2%, 21/172) were the most common congenital malformations in Chinese children with FA. No significant difference was found in the number of congenital malformations between children with severe (50 cases) and mild FANCA variants (26 cases) (Z=-1.33, P=0.185). Conclusions: FANCA gene is the main pathogenic gene in children with FA, where the detection of its exon deletion should be strengthened clinically. There were no phenotypic differences among children with different types of FANCA variants. Chromosome break test is helpful to determine the pathogenicity of variants, but its accuracy needs to be improved.
Male ; Female ; Humans ; Child ; Fanconi Anemia/genetics* ; Chromosome Breakage ; Retrospective Studies ; Exons ; China/epidemiology*

Objective:To recognize the overall situation of the core competency of medical professional postgraduate, analyze the advantages and disadvantages of the training process, and provide basis for better optimization and revision of training objectives and training plans.Methods:An anonymous online questionnaire was conducted among 264 postgraduates majoring in clinical medicine to recognize the cognition and self-evaluation of core competence, and analyze the differences in scores of different grades and types. SPSS 23.0 was used for independent-samples t test; and one-way analysis of variance to analyze categorical variables. Results:The doctoral degree students' core competency results were higher than those of master degree students, and those of the senior students were higher than junior students ( P<0.05). "System Improvement Ability" [master degree students (2.94±1.07), first-year students (2.82±0.97)], "Patient Management" [(first-year students (2.77±1.22)], "Academic Research" [first-year students (2.90±1.03)], and 4 other indicators were the weakness of students (all less than 3 scores). Conclusion:The students have a good sense of professional identity for doctors. The different depth of the clinical practice education is the possible cause which brings about the differences among students with different degrees. We should focus on strengthening the training for the "shortcomings" in the core competence of students.

Abstract: Objective To explore the influencing factors of serum HBeAg loss in patients with chronic hepatitis B (CHB) and and provide evidence for effective treatment of CHB. Methods A follow-up cohort of HBeAg-positive CHB patients was established in the the Infectious Diseases Outpatient Clinic of hospital. Regular follow-up and laboratory test indicators were collected to analyze the changes of serum HBeAg in HBeAg-positive CHB patients during the follow-up period. The subjects were divided into the case group (serum HBeAg loss) and the control group (serum HBeAg not loss) according to whether serum HBeAg loss occurred. The baseline data characteristics of the two groups were analyzed and compared, and the influencing factors of serum HBeAg loss were analyzed by Cox univariate and multivariate regression. Results A total of 634 HBeAg-positive CHB patients were enrolled, with a total follow-up of 2 570.01 person-years. Among them, 237 cases of serum HBeAg loss occurred, with the mean follow-up time of 40.92 months, and the rate of HBeAg loss was 9.22/100 person-years. There were significant differences in HBV family history, antiviral therapy, baseline WBC, PLT, ALT, AST, T˗Bil, GGT, AFP, quantitative HBsAg and quantitative HBeAg between serum HBeAg loss group and serum HBeAg not loss group (P<0.05). Cox regression analysis showed that family history of HBV (HR 0.68, 95％CI:0.50-0.92, P=0.012), ALT (HR2.06, 95％CI:1.52-2.79, P<0.001), quantitative HBsAg (HR 0.68, 95％CI:0.48-0.95, P=0.024), quantitative HBeAg (HR 0.48, 95％CI:0.31-0.74, P=0.001) were independent influencing factors for HBeAg loss in HBeAg-positive CHB patients. Conclusions HBeAg-positive CHB patients without family history of HBV, initial ALT≥80 U/L, quantitative HBsAg<1 000 IU/ml, quantitative HBeAg<1 000 C.O.I are more likely to have serum HBeAg loss.

Objective: Retrospective analysis of the efficacy and influencing factors of bladder preservation integrated therapy for unresectable invasive bladder cancer confined to the pelvis was done, also including the bladder function preservation and adverse effects analysis. Methods: Sixty-nine patients with unresectable locally invasive bladder cancer who received radiotherapy-based combination therapy from March 1999 to December 2021 at our hospital were selected. Among them, 42 patients received concurrent chemoradiotherapy, 32 underwent neoadjuvant chemotherapyand 43 with transurethral resection of bladder tumors (TURBT) prior to radiotherapy. The late adverse effect of radiotherapy, preservation of bladder function, replase and metastasis and survival were followed-up. Cox proportional hazards models were applied for the multifactorial analysis. Results: The median age was 69 years. There were 63 cases (91.3%) of uroepithelial carcinoma, 64 of stage Ⅲ and 4 of stage Ⅳ. The median duration of follow-up was 76 months. There were 7 grade 2 late genito urinary toxicities, 2 grade 2 gastrointestinal toxicities, no grade 3 or higher adverse events occurred. All patients maintained normal bladder function, except for 8 cases who lost bladder function due to uncontrolled tumor in the bladder. Seventeen cases recurred locally. There were 11 cases in the concurrent chemoradiotherapy group with a local recurrence rate of 26.2% (11/42) and 6 cases in the non-concurrent chemoradiotherapy group with a local recurrence rate of 22.2% (6/27), and the difference in local recurrence rate between the two groups was not statistically significant (P=0.709). There were 23 cases of distant metastasis (including 2 cases of local recurrence with distant metastasis), including 10 cases in the concurrent chemoradiotherapy group with a distant metastasis rate of 23.8% (10/42) and 13 cases in the non-concurrent chemoradiotherapy group with a distant metastasis rate of 48.1% (13/27), and the distant metastasis rate in the non-concurrent chemoradiotherapy group was higher than that in the concurrent chemoradiotherapy group (P=0.036). The median 5-year overall survival (OS) time was 59 months and the OS rate was 47.8%. The 5-year progression-free survival (PFS) time was 20 months and the PFS rate was 34.4%. The 5-year OS rates of concurrent and non-concurrent chemoradiotherapy group were 62.9% and 27.6% (P<0.001), and 5-year PFS rates were 45.4% and 20.0%, respectively (P=0.022). The 5-year OS rates of with or without neoadjuvant chemotherapy were 78.4% and 30.1% (P=0.002), and the 5-year PFS rates were 49.1% and 25.1% (P=0.087), respectively. The 5-year OS rates with or without TURBT before radiotherapy were 45.5% and 51.9% (P=0.233) and the 5-year PFS rates were 30.8% and 39.9% (P=0.198), respectively. Multivariate Cox regression analysis results showed that the clinical stage (HR=0.422, 95% CI: 0.205-0.869) was independent prognostic factor for PFS of invasive bladder cancer. The multivariate analysis showed that clinical stages (HR=0.278, 95% CI: 0.114-0.678), concurrent chemoradiotherapy (HR=0.391, 95% CI: 0.165-0.930), neoadjuvant chemotherapy (HR=0.188, 95% CI: 0.058-0.611), and recurrences (HR=10.855, 95% CI: 3.655-32.638) were independent prognostic factors for OS of invasive bladder cancer. Conclusion: Unresectable localized invasive bladder cancer can achieve satisfactory long-term outcomes with bladder-preserving combination therapy based on radiotherapy, most patients can retain normal bladder function with acceptable late adverse effects and improved survival particularly evident in patients with early, concurrent chemoradiotherapy and neoadjuvant chemotherapy.
Humans ; Aged ; Treatment Outcome ; Retrospective Studies ; Combined Modality Therapy ; Chemoradiotherapy/methods* ; Urinary Bladder Neoplasms/radiotherapy* ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Neoplasm Staging

Objective:To screen the endoplasmic reticulum stress (ERS) signature-related differentially expressed genes (DEG) in gastric cancer and to construct a prognostic risk model based on a bioinformatics.Methods:Transcriptome sequencing data (RNA-seq) of 375 gastric cancer and 32 paracancerous tissue samples downloaded from The Cancer Genome Atlas (TCGA) database and the corresponding clinical information were obtained as training set samples; data of 387 gastric cancer patients (GSE84437) from Gene Expression Omnibus (GEO) database were downloaded as validation set samples. All data were obtained on December 25, 2021. A total of 785 ERS signature-related genes (ERS-RG) were obtained from the GeneCards database. DEG between gastric cancer tissues and paracancerous tissues in the TCGA database was analyzed. The identified gastric cancer DEG were intersected with ERS-RG from the GeneCards database to obtain gastric cancer ERS signature-related DEG, which were analyzed for gene ontology (GO) function and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment. Univariate Cox proportional risk model was used to screen ERS signature-related DEG with prognostic value in gastric cancer, and LASSO regression analysis was performed to construct a polygenic prognostic risk model, and to calculate the prognostic risk score. The patients in training set and validation set were divided into high-risk group and low-risk group according to the median of the prognostic risk score (2.369); Kaplan-Meier survival analysis was used to compare the overall survival (OS) and to draw time-dependent receiver operating characteristic (ROC) curves of patients in the two groups; nomogram was drawn based on the prognostic independent influencing factors of gastric cancer. The characteristic immune cell infiltration abundance between the two groups was analyzed by using the inverse convolution-based CIBERSORT algorithm. Cytolytic activity scores were calculated by using the geometric mean of granzyme A and perforin 1 expression. According to the median prognostic risk score (2.369) and median tumor mutation burden (TMB) (3.000), all patients with gastric cancer were divided into high risk score-high TMB group, high risk score-low TMB group, low risk score-high TMB group and low risk score-low TMB group to compare the OS of patients in each group.Results:A total of 444 ERS signature-related DEG in gastric cancer including 168 down-regulated genes and 276 up-regulated genes were obtained, which were mainly enriched in biological processes such as protein processing in the endoplasmic reticulum, extracellular matrix (ECM) receptor interactions and unfolded protein responses (all P < 0.05). Univariate Cox regression analysis showed that 12 prognostic-related ERS signature-related DEG in gastric cancer were screened out. LASSO regression analysis was performed to obtain a prognostic risk score = 0.052×NOS3+0.137×PON1+0.067×CXCR4+0.131×MATN3+0.116×ANXA5+0.090×SERPINE1. The results of Kaplan-Meier analysis showed that the OS of the low-risk group in both the training and validation sets was better than that of the high-risk group (all P < 0.01). The results of the time-dependent ROC curve analysis showed that the AUC for the 3-year, 5-year, 8-year OS rates was 0.695, 0.786, 0.698, respectively in the training set, while the AUC for the 3-year 5-year, 8-year OS rates was 0.580, 0.625, 0.627, respectively in the validation set. Multivariate Cox regression analysis showed that prognostic risk score ( HR = 3.598, 95% CI 2.290-5.655, P < 0.001) and tumor stage ( HR = 1.344, 95% CI 1.057-1.709, P < 0.05) were independent factors influencing the prognosis of gastric cancer. Among 375 gastric cancer patients in the TCGA database, the expression levels of ATF6, HSPA5, XBP1 and ATF4 in the high-risk group were higher than those in the low-risk group (all P < 0.05); CIBERSORT results showed that the abundance of activated CD4 memory T cells in the high-risk group was lower than that in the low-risk group, and the abundance of both M0 and M2 macrophages in the high-risk group was higher than that in the low-risk group (all P < 0.05). The expression levels of common immune checkpoints (CD274, CTLA4, TNFRSF9, TIGIT, PDCD1, LAG3) in the high-risk group were all higher than those in the low-risk group (all P < 0.05). Cytolytic activity score in the high-risk group was higher than that in the low-risk group ( P < 0.05). The prognostic risk score was negatively correlated with TMB ( r = -0.20, P < 0.001). Patients in the low-risk score-high TMB group had the best OS and those in the high-risk score-low TMB group had the worst OS (both P < 0.001). Conclusions:The prognostic risk score model is established based on 6 ERS signature-related DEG in gastric cancer and its prognostic risk score may be effective as an independent prognostic factor to predict the prognosis of gastric cancer patients.

As arsenic widely exists in nature and has been used in the pharmaceutical preparations, the traditional Chinese medicine(TCM) with arsenic include realgar(As_2S_2 or As_4S_4), orpiment(As_2S_3), and white arsenic(As_2O_3). Among the above representative medicine, the TCM compound formulas with realgar are utilized extensively. Just in Chinese Pharmacopoeia(2020 edition), there are 37 Chinese patent medicines including realgar. The traditional element analysis focuses on the detection of the total amount of elements, which neglects the study on the speciation and valence of elements. The activity, toxicity, bioavailability, and metabolic pathways of arsenic in vivo are closely related to the existence of its form, and different forms of arsenic have different effects on organisms. Therefore, the study on the speciation and valence of arsenic is of great importance for arsenic-containing TCMs and their compound formulas. This paper reviewed four aspects of the speciation and valence of arsenic, including property, absorption and metabolism, toxicity, and analytical assay.
Arsenic/analysis* ; Arsenicals/analysis* ; Sulfides ; Arsenic Trioxide ; Medicine, Chinese Traditional ; Drugs, Chinese Herbal/analysis* ; Biological Products

Fermented Chinese medicine has long been used. Amid the advance for preservation of experience, the connotation of fermented Chinese medicine has been enriched and improved. However, fermented Chinese medicine prescriptions generally contain a lot of medicinals. The fermentation process is complicated and the conventional fermentation conditions fail to be strictly controlled. In addition, the judgment of the fermentation end point is highly subjective. As a result, quality of fermented Chinese medicine is of great difference among regions and unstable. At the moment, the quality standards of fermented Chinese medicine are generally outdated and different among regions, with simple quality control methods and lacking objective safe fermentation-specific evaluation indictors. It is difficult to comprehensively evaluate and control the quality of fermented medicine. These problems have aroused concern in the industry and also affected the clinical application of fermented Chinese medicine. This article summarized and analyzed the application, quality standards, and the modernization of fermentation technology and quality control methods of fermented Chinese medicine and proposed suggestions for improving the quality standards of the medicine, with a view to improving the overall quality of it.
Medicine, Chinese Traditional ; Reference Standards ; Quality Control ; Fermentation

According to the polarity of different components in Sanpian Decoction, two fingerprints were established. Then the substance benchmark freeze-dried powder of 15 batches of Sanpian Decoction was prepared, followed by the determination of the fingerprints, index component content, and dry extract rates, the identification of attribution of characteristic peaks, and the calculation of similarities between these fingerprints and the reference(R), the content and transfer rate ranges of ferulic acid, sinapine thiocyanate, liquiritin, and glycyrrhizic acid, and the dry extract rate range. The results showed that the similarities of 15 batches of the substance benchmark fingerprints with R were all greater than 0.900.Further summarization of the characteristic peaks revealed that there were a total of 20 characteristic peaks in fingerprint 1, among which, eight were from Sinapis Semen, four from Paeoniae Radix Alba, six from Chuanxiong Rhizoma, and two from Glycyrrhizae Radix et Rhizoma. A total of 16 characteristic peaks were observed in fingerprint 2, including one from Sinapis Semen, three from Paeoniae Radix Alba, eight from Chuanxiong Rhizoma, and four from Glycyrrhizae Radix et Rhizoma. The average dry extract rate of 15 batches of substance benchmarks was 18.25%, with a dry extract rate range of 16.28%-20.76%. The index component content and transfer rate ranges were listed as follows: 0.15%-0.18% and 38.81%-58.05% for ferulic acid; 0.26%-0.42% and 36.51%-51.02% for sinapine thiocyanate; 0.09%-0.15% and 48.80%-76.61% for liquiritin; 0.13%-0.24% and 23.45%-35.61% for glycyrrhizic acid. The fingerprint, dry extract rate, and index component content determination was combined for analyzing the quality value transfer of substance benchmarks in the classic prescription Sanpian Decoction.The established quality evaluation method for the substance benchmarks was stable and feasible, which has provided a basis for the quality control of Sanpian Decoction and the follow-up development of related preparations.
Benchmarking ; Chromatography, High Pressure Liquid ; Drugs, Chinese Herbal ; Glycyrrhizic Acid/analysis* ; Paeonia ; Quality Control ; Thiocyanates