Objective To analyze the prognostic factors in the patients with HER2-positive breast cancer adjuvant treated with trastuzumab.Methods We conducted a retrospective analysis of clinical data of 1 246 patients diagnosed with HER2-positive breast cancer between January 2009 and December 2019 who received treatment with trastuzumab.We investigated the factors impacting their prognosis by the Log-rank test univariate analysis and multivariate COX regression analysis.Results HER2-positive patients treated with trastuzumab had a poor prognosis in pT2-3(HR=2.10,P=0.003),pN2-3(HR=2.81,P<0.001),and no endocrine therapy(HR=2.50,P<0.001),and that had a better prognosis combined with taxane or other chemotherapy regimens(HR=0.40,P=0.017).We divided the patients into two subgroups according to the status of lymph node metastasis,and we found that in the negative lymph nodes group the patients with pT2-3 stage had poor prognosis(P=0.020),while the patients combined with taxane or other chemotherapy had better prognosis(P=0.032).In the positive lymph nodes group the patients with pT2-3 stage and no endocrine therapy had poor prognosis(P=0.012,P=0.001).Conclusions The patients with HER2-positive breast cancer treated with trastuzumab can be managed in different categories,for individuals without lymph node involvement and small tumor sizes,combining therapy with non-anthracycline chemotherapy is preferable for achieving improved outcomes,for patients with lymph node metastasis and large tumor sizes,if chemotherapy options are available,it is more recommended to use an anthracycline-free regimen to ensure the same prognosis while reducing the harm caused by the toxic side effects of chemotherapy.

Objective:To explore the biological role and clinical significance of ubiquitin-specific protease 7 (USP7) in the carcinogenesis of scar ulcer.Methods:A retrospective observational study combined with bioinformatics analysis was used. The RNA expression profile data of USP7 in tumor and/or its corresponding paracancular normal tissue were obtained from The Cancer Genome Atlas (TCGA) database and the Gene Expression Omnibus database, and the RNA sequencing data were transformed by log 2. The variations of USP7 gene were analyzed by cBioPortal database. The USP7 mRNA expression in tumor and adjacent normal tissue in TCGA database were obtained by using the "Gene_DE" module in TIMER 2.0 database. The survival rates of patients with high and low USP7 expression in cutaneous melanoma (SKCM), cervical squamous cell carcinoma (CESC), lung squamous cell carcinoma (LUSC), and head and neck squamous cell carcinoma (HNSC) were analyzed using the Gene Expression Profile Interactive Analysis 2 (GEPIA2) database, and the Kaplan-Meier survival curves were drawn. Sangerbox database was used to analyze the correlation of USP7 expression in pan-cancer with microsatellite instability (MSI) or tumor mutation burden (TMB) pan-cancer. Through the "correlation analysis" module in the GEPIA2 database, the correlation of USP7 expression in pan-cancer with the expression levels of five DNA mismatch repair genes ( MLH1, MSH2, MSH6, PMS2, and EPCAM) and three essential DNA methyltransferases (DNMT)--DNMT1, DNMT3A, and DNMT3B were evaluated. The USP7 expression in CESC, HNSC, LUSC, and SKCM and its correlation with infiltration of immune cells (B cells, CD4 + T cells, CD8 + T cells, neutrophils, macrophages, and dendritic cells) were analyzed by the "Immune-Gene" module in TIMER 2.0 database. The "Similar Genes Detection" module of GEPIA2 database was used to obtain the top 100 protein sets with similar expression patterns to USP7. Intersection analysis was performed between the aforementioned protein sets and the top 50 protein sets that were directly physically bound to USP7 obtained by using the STRING database. Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) enrichment analysis were performed for the two protein sets mentioned above using the DAVID database. The samples of normal skin, hypertrophic scar, scar ulcer, and scar carcinoma with corresponding clinicopathologic features were collected from the Department of Pathology of Tongren Hospital of Wuhan University & Wuhan Third Hospital from October 2018 to October 2022, and the USP7 expression in tissue was detected by immunohistochemical method, with the number of samples of 6. Data were statistically analyzed with Log-rank test, one-way analysis of variance, and Bonferroni test. Results:In pan-cancer, the main gene variations of USP7 were mutation and amplification, and the top 3 tumors with the highest variation frequency (>6%) were bladder urothelial carcinoma, SKCM, and endometrial carcinoma. The main mutation of USP7 gene in pan-cancer was missense mutation. In SKCM with the highest mutation frequency, the main type of mutation was missense mutation in USP7_ICP0_bdg domain. USP7 mRNA expression in breast invasive carcinoma, bile duct carcinoma, colon carcinoma, esophageal carcinoma, HNSC, renal chromophobe cell carcinoma, hepatocellular carcinoma, lung adenocarcinoma, LUSC, prostate carcinoma, and gastric carcinoma was significantly higher than that in corresponding paracancer normal tissue ( P<0.05). USP7 mRNA expression in glioblastoma multiforme, renal clear cell carcinoma, renal papillary cell carcinoma, and thyroid carcinoma was significantly lower than that in corresponding paracancular normal tissue ( P<0.05). In addition, USP7 mRNA expression in SKCM metastases was much higher than that in primary tumor tissue ( P<0.05). Survival curves showed no significant difference in survival rate between patients with high USP7 expression and patients with low USP7 expression in CESC, HNSC, LUSC, and SKCM (Log-rank P>0.05, with hazard ratios of 1.00, 0.99, 1.00, and 1.30, respectively). USP7 expression in colon cancer, colorectal cancer, thymic cancer, and thyroid cancer was negatively correlated with TMB (with Pearson correlation coefficients of -0.26, -0.19, -0.19, and 0.11, respectively, P<0.05). USP7 expression in glioma, CESC, lung adenocarcinoma, mixed renal carcinoma, and LUSC was positively correlated with MSI expression (with Pearson correlation coefficients of 0.22, 0.14, 0.15, 0.08, and 0.14, respectively, P<0.05), and USP7 expression in colon cancer, colorectal cancer, invasive breast cancer, prostate cancer, HNSC, thyroid cancer, and diffuse large B-cell lymphoma were significantly negatively correlated with MSI expression (with Pearson correlation coefficients of -0.31, -0.27, -0.13, -0.19, -0.16, -0.18, and -0.53, respectively, P<0.05). The expression of USP7 in CESC was positively correlated with that of both MSH2 and MSH6 (with Spearman correlation coefficients of 0.51 and 0.44, respectively, P<0.05), and the expression of USP7 in HNSC was positively correlated with the expression of EPCAM, MLH1, MSH2, MSH6, and PMS2 (with Spearman correlation coefficients of 0.39, 0.14, 0.49, 0.54, and 0.41, respectively, P<0.05), and the expression of USP7 in LUSC was positively correlated with the expression of EPCAM, MSH2, MSH6, and PMS2 (with Spearman correlation coefficients of 0.20, 0.36, 0.40, and 0.34, respectively, P<0.05), and the expression of USP7 in SKCM was positively correlated with the expression of EPCAM, MLH1, MSH2, MSH6, and PMS2 (with Spearman correlation coefficients of 0.11, 0.33, 0.42, 0.55, and 0.34, respectively, P<0.05). The expression of USP7 in CESC, HNSC, LUSC, and SKCM was significantly positively correlated with the expression of DNMT1, DNMT3A, and DNMT3B (with Spearman correlation coefficients of 0.42, 0.34, 0.22, 0.45, 0.52, 0.22, 0.36, 0.36, 0.22, 0.38, 0.46, and 0.21, respectively, P<0.05). The expression of USP7 in CESC, HNSC, LUSC, and SKCM was positively correlated with CD4 + T cell infiltration (with Partial correlation coefficients of 0.14, 0.22, 0.13, and 0.16, respectively, P<0.05). Being similar to the pattern of USP7 expression and ranked among top 100 protein sets, the top 5 proteins were C16orf72, BCLAF1, UBN, GSPT1, ERI2 (with Spearman correlation coefficients of 0.83, 0.74, 0.73, and 0.72, respectively, all P values<0.05). The top 50 protein sets that directly physically bind to USP7 overlapped with the aforementioned protein set by only one protein, thyroid hormone receptor interaction factor 12. KEGG enrichment analysis showed that USP7 related genes were involved in cell cycle, spliceosome, cell senescence, and p53 signal pathway. GO enrichment analysis showed that USP7 related genes were involved in transcriptional regulation, protein ubiquitination, DNA repair, and cytoplasmic pattern recognition receptor signal pathways. Analysis of clinical samples showed that USP7 expression was significantly higher in hypertrophic scars (0.35±0.05), scar ulcers (0.43±0.04), and scar cancers (0.61±0.03) than in normal skin (0.18±0.04), P<0.05. Conclusions:USP7 may be a clinical biomarker for the progression of cicatricial ulcer cancer.

Objective:To study the relationship of pathogenic bacteria in midstream urine culture and stone composition of patients characteristics with infection stones.Methods:Between January 2016 and December 2020, 989 patients with infectious stones who attended Tsinghua Chang Gung Hospital, affiliated with Tsinghua University, for surgical treatment were enrolled in the study. There were 545 male and 444 female patients, with the mean age (48±14) years. The left and right side stones were 396 and 333, respectively. There were 260 bilateral stones, 264 single stones, 334 multiple stones, and 391 deer-stalker-shaped stones. The maximum diameter of stones was (33.4±26.5)mm, combined with diabetes in 109 cases and hypertension in 235 cases. Clean middle-urine was collected for bacterial culture, and intraoperative stone specimens were collected by percutaneous nephrolithotomy (PCNL). Personal characteristics of the patient such as gender, age, body mass index, clinical information such as stone size, location, comorbidities, results of urine culture and stone composition were recorded. The differences of infectious stone composition was analyzed between urease-producing, non-urease-producing bacteria.Results:Among the 989 patients with infectious stones, 259 were pure infectious stones, 131 were mixed infectious stones, and 599 were combined with infectious stone components. Urine cultures were positive in 627(63.4%) patients with infectious stones. The predominant urease-producing bacteria included Ureaplasma urealyticum(94 case), Proteus mirabilis(58 case), and Staphylococcus spp.(36 case). Pure infectious stones were common in Proteus mirabilis, while combined with infectious stone components were common in Ureaplasma urealyticum and Staphylococcus spp. The predominant non-urease-producing bacteria included Escherichia coli(175 case), Enterococcus spp.(76 case) and Streptococcus spp.(35 case). Escherichia coli commonly contained in infectious stone components and pure infectious stones, whereas Enterococcus spp. and Streptococcus spp. commonly contained in infectious stone components. Escherichia coli (61 case), Proteus mirabilis (44 case) and Enterococcus spp.(20 case) were the most common bacteria in 259 cases of pure infectious stones. Escherichia coli (36 case), Enterococcus spp. (14 case) and Ureaplasma urealyticum (10 case) were the most common bacteria in 131 cases of mixed infectious stones. The most common bacteria in 599 cases of combined infectious stones were Escherichia coli (78 case), Ureaplasma urealyticum (68 case) and Enterococcus spp. (42 case).Conclusions:Urease producing bacteria were not common in infectious stones. It was common for the Ureaplasma urealyticum in combined infectious stone components, while Escherichia coli was common in pure and combined infectious stone components.

Objective:To identify the factors associated with long-term survival and guide the decision for primary surgery in patients with advanced high-grade serous ovarian cancer(HGSOC).Methods:In this case-control study, clinical parameters, including surgical and non-surgical associated factors, were collected and compared between the patients with short-term (<2 years) and long-term (>5 years) survival who all underwent primary debulking surgery (PDS) followed by carboplatin and paclitaxel chemotherapy from January 2004 to December 2016. Univariate analysis was examined by chi-square test and multivariate analysis was performed by logistic regression analysis.Results:There were 95 cases long-term survival (LTS group) and 77 cases short-term survival (STS group) in 698 newly diagnosed HGSOC patients with International Federation of Gynecology and Obstetrics (FIGO) stage Ⅲc and Ⅳ who met include and exclude criteria. (1) Univariate analysis showed that the proportion of complete cytoreduction with no visible residual disease (R0) at PDS and platinum sensitivity in LTS group were significantly higher than those in STS group ( P<0.01). The surgical complexity score (SCS), the preoperative serum CA 125 level and the ascites volume in the LTS group were significantly lower than those of the STS group (all P<0.05). In the LTS group, the preoperative incidence of lesions in retrograde peritoneum of the bladder, serosal and mesangial membrane of the small intestine, upper abdominal peritoneum and liver parenchyma were significantly lower than those in the STS group (all P<0.05). Multivariate logistic regression analysis showed that platinum sensitivity ( OR=0.016, 95% CI: 0.004-0.063, P<0.01), ascites volume >500 ml ( OR=3.193, 95% CI: 1.285-7.930, P=0.012), and SCS ≥8 ( OR=17.433, 95% CI: 2.281-133.25, P=0.003) were independent factors affecting long-term survival ( P>0.05). (2) Totally 37 of 95 in long-term survival and 16 of 77 in short-term survival achieved R0 cytoreduction at PDS. Univariate analysis showed that preoperative serum CA 125 level, preoperative lesion score, preoperative lesion (DS) score, ascites volume, platinum sensitivity,and SCS were significantly correlated with the R0 PDS (all P<0.05). Multivariate analysis showed that ascites volume >500 ml ( OR=5.199, 95% CI: 2.015-13.409, P=0.001), DS >2 ( OR=15.264, 95% CI: 5.843-39.874, P<0.01) and SCS ≥4 ( OR=4.176, 95% CI: 1.618-10.777, P=0.003) were independent factors associated with R0 cytoreduction. In patients with DS ≤2 or SCS <4, but not those with DS >2 or SCS ≥4, R0 cytoreduction was significantly associated with long-term survival. Conclusion:The intrinsic biology of tumor is the factor influencing long-term survival of advanced HGSOC patients, and those who present with wide intraperitoneal metastases and need to remove multiple organs may not benefit from R0 cytoreduction.

Objective:To introduce the preliminary experience of domestic disposable digital flexible ureteroscope (ZebraScope?)in the treatment of upper urinary calculi.Methods:The clinical data of 16 patients with upper urinary calculi treated by ZebraScope? in our hospital from February to March 2020 were retrospectively analyzed. The scope is composed of a handle and shaft, the image can be transferred through the transmission line at the end of the handle. There were 10 males and 6 females. The mean age was 42.1 years (26-63 years). 12 cases of upper ureteral calculi and 4 cases of renal calculi included. Mean diameter was 1.3cm (0.8-2.1cm). Ureteral stents were preoperatively placed in 4 patients and no pre-stent were in 12 patients. Two patients had a history of endoscopic lithotripsy. The ureteral sheath was used in 4 patients with F12/14, 10 patients with F11/13, and 2 patients with F10/12. Eight patients were treated with a stone basket. Intra-operative lithotripsy was performed using 200um optical fiber combined with holmium laser, and 6Fr ureteral stent was routinely indwelling for 2-4 weeks. The operation time, postoperative complications, hospital-in time, stone clearance rate and other related parameters were summarized and analyzed.Results:Of the 16 patients, 14 succeed and 2 patients failed and secondary operation was applied due to poor ureteral condition. The mean operative time was 55.6 minutes (32-115 minutes). The average laser emission time was 25.2 minutes (10-65 minutes). There was no image degradation and scope damage during the operation. All the patients recovered well after the operation, and no postoperative complications such as fever and pain occurred. Two patients received external physical vibration lithecbole therapy. The average hospital-in time was 1.2 days (1-3 days). One month after the operation, the calculi clearance rate was 87.5% (14/16).Conclusion:Our preliminary study found that ZebraScope? could be safe and effective in the treatment of upper urinary calculi less than 2 cm. Futhter verification is required in larger renal stones.

Purpose: This retrospective study aimed to evaluate the distribution pattern and prognostic value of 21-gene recurrence score (RS) in Chinese patients with mucinous breast cancer (MC) and compared with infiltrating ductal carcinoma (IDC). Materials and Methods: Patients diagnosed with MC or IDC from January 2010 to January 2017 were retrospectively recruited. Reverse transcriptase–polymerase chain reaction assay of 21 genes was conducted to calculate the RS. Univariate and multivariate analyses were performed to assess the association between RS and clinicopathological factors. Survival outcomes including disease-free survival (DFS) and overall survival (OS) were estimated by Kaplan-Meier method and compared by log-rank test. Results: The MC cohort included 128 patients and the IDC cohort included 707 patients. The proportions of patients with a low (RS < 18), intermediate (18-30), or high risk (RS > 30) were 32.0%, 48.4%, and 19.5% in MC cohort, and 26.9%, 46.8% and 26.3% in IDC cohort. The distribution of RS varied significantly according to different Ki-67 index and molecular subtype in both cohorts. Moreover, the receipt of chemotherapy was associated with RS in both cohorts. Among patients with MC, tumor stage was related to the DFS (p=0.040). No significant differences in DFS and OS were found among MC patients in different RS risk groups (OS, p=0.695; DFS, p=0.926). Conclusion RS was significantly related to Ki-67 index and molecular subtypes in MC patients, which is similar in IDC patients. However, RS was not able to predict DFS and OS in patients with MC.

OBJECTIVE: To report on the clinical pictures of 7 patients from a pedigree affected with X-linked adrenal hypoplasia congenita (XL-AHC) and hypogonadotropic hypogonadism (HH) and the underlying mutations. METHODS: Seven patients were identified from a four-generation pedigree affected with XL-AHC and HH. Their clinical features, endocrinological changes, treatment and drug response were recorded. The patients were subjected to next-generation sequencing, and the result was verified by Sanger sequencing. PolyPhen-2 was used for predicting the influence of the mutation on protein production. RESULTS: Three deceased patients had manifested adrenal insufficiency (AI) within one year after birth. Two died at 6 and one died at 12. The four survivors presented with salient clinical and endocrinological features of AHC and HH, adrenal and testicular atrophy, and renin-angiotensin compensation. Two adult patients had testicular micro-stone detected by ultrasound.One of them also had remarkable seminiferous tubule degeneration by biopsy. The patients were followed up for 0.5 to 10 years. All required hyper-physiological dose of hydrocortisone to stabilize their clinical condition. In three patients, gonadotropic or androgen replacement induced cardinal masculine development but with unsatisfactory testis growth and sperm production.Genetic analysis revealed a novel missense c.827A>C (p.Q276P) mutation in a hotspot region within a highly conserved domain. PolyPhen-2 predicted the mutation to be highly hazardous. CONCLUSION The novel p.Q276P mutation of the DAX1 gene probably underlies the XL-AHC and HH in this pedigree with variable clinical presentations in the patients.
Adrenal Insufficiency ; DAX-1 Orphan Nuclear Receptor ; genetics ; Humans ; Hypoadrenocorticism, Familial ; genetics ; Male ; Mutation ; Mutation, Missense ; Pedigree ; Repressor Proteins

Objective: To analyze the association between clinicopathological factors and clinical diagnosis, treatment and surgery of local regional recurrence (LRR) in breast cancer. Methods: A retrospective study was done to evaluate consecutive 7 823 breast cancer LRR cases between January 2009 and August 2018 at Comprehensive Breast Health Center, Ruijin Hospital, Shanghai Jiaotong University School of Medicine. A total of 108 LRR patients were enrolled: 35 cases (32.4%) with ipsilateral breast tumor recurrence (IBTR) after breast conserving surgery, 40 cases (37.0%) of chest wall recurrence (CR), and 33 cases (30.6%) with regional lymph node recurrence (LNR). All patients were female, aged from 26 to 83 years with a mean of 49 years. Clinicopathological factor and its relationship with different sites of LRR and following surgical choice were analyzed by χ² test, rank-sum test and Logistic regression. Survival analysis were performed between different LRR patterns and whether undergoing second surgery. Kaplan-Meier survival curves and Log-rank tests demonstrated the distribution of overall survival. Results: Both univariate analysis and multivariate analysis found that axillary lymph nodes (ALN) status (OR=7.27, 95% CI: 1.30 to 40.53, P=0.042) and disease-free interval (OR=0.18, 95% CI: 0.06 to 0.60, P=0.013) were related to different site of LRR. Compared with patients with IBTR, LNR and CR patients had a higher rate of ALN metastasis and a shorter disease-free interval. A total of 36 LRR patients underwent following surgery. In univariate analysis, initial ALN surgery (χ²=16.705, P=0.001), pathological type (χ²=7.047, P=0.03), ALN status (χ²=10.812, P=0.002), disease-free interval (χ²=6.118, P=0.023) and LRR site(χ²=19.328, P=0.000) were associated with surgical treatment for LRR patients. Multivariate analysis demonstrated that only site of LRR was independently associated with surgery (OR=0.17, 95% CI: 0.05 to 0.65, P=0.024). The 5-year overall survival was 100% and 60.1% (P=0.018) for LRR patients treated with surgery or not. Furthermore, CR patients had significantly worse overall survival than LNR and IBTR patients, with 5-year overall survival 53.1%, 73.5%, and 100% respectively (P=0.021). Conclusions Initial lymph nodes metastasis and disease-free interval are associated with different site of LRR. LRR site significantly influenced following surgery choice after LRR, which are both related with overall survival after LRR.

Objective: To survey the conduction and evaluate the effectiveness of extracorporeal membrane oxygenation (ECMO) therapy in pediatric intensive care unit (PICU) in China mainland. Methods: In a questionnaire-based survey, we retrospectively reviewed the application of ECMO in children's hospital and general hospital in China mainland to summarize and analyze the categories of diseases and prognosis of children treated with ECMO therapy. Results: By December 31, 2017, a total of 23 hospitals using ECMO, including 22 tertiary referral hospitals and 1 secondary hospital, among which 16 were children′s hospitals and 7 were general hospitals. Thirty-seven ECMO equipment was available. A total of 518 patients treated with ECMO, within whom 323 (62.4%) successfully weaned from ECMO and 262 (50.6%) survived to discharge. Among 375 pediatric patients, 233 (62.1%) were successfully weaned from ECMO and 186 (49.6%) survived to discharge. Among 143 newborn patients, 90 (62.9%) successfully weaned from ECMO, 76 (53.1%) survived to discharge. ECMO was applied in veno-arterial (VA) mode to 501 (96.7%) patients, veno-venous (VV) mode to 14 (2.7%) patients, and VV-VA conversion mode to 3 (0.6%) patients. Sixty-nine patients required extracorporeal cardiopulmonary resuscitation (ECPR), including 20 newborn patients (29.0%) and 38 pediatric patients (71.0%), who were all with cardiovascular disease. Neonatal respiratory distress syndrome (26/61), persistent pulmonary hypertension of the newborn (PPHN) (12/61), and meconium aspiration syndrome (MAS) (11/61) are the most common pulmonary diseases in newborn patients; among whom, infants with PPHN had highest survival rate (10/12), followed by MAS (9/11). Among newborn patients with cardiovascular diseases, those who admitted were after surgery for congenital cardiac disease were the most common (54/82), while those with septic shock had the highest survival rate (2/3). In pediatric pulmonary diseases, acute respiratory distress syndrome was the most common (42/93), while plastic bronchitis was with the highest survival rate (4/4), followed by viral pneumonia (13/16). Among pediatric cardiovascular diseases, congenital cardiac defect was the most common (124/282), while fulminant myocarditis had the highest survival rate (54/77). Conclusion The application of ECMO as a rescue therapy for children with severe cardiopulmonary failure has dramatically developed in China mainland.

Objective To study the effect of electroacupuncture on the behavior of APP/PS1 transgenic mice of different age, and to explore the optimal intervention time of electroacupuncture in treating Alzheimer's disease (AD). Method APP/PS1 double-transgenic mice of 4 months, 6 months and 9 months old, 20 in each age group, were randomized into a model group and an electroacupuncture group, and ten C57BL/6 wild-type mice were taken as a control group; after 6-week electroacupuncture treatment, the Morris water maze was adopted for spatial memory and behavioral test, and the changes of behavior in each group were observed.Result Of the 5-month-old mice, there were no significant between-group differences (P>0.05), while the time factor (day) produced a statistical significance (P<0.01); of the 7-month-old mice, there were significant differences considering the different groups, time factor and interaction (P<0.01); of the 10-month-old mice, there were significant differences considering the different groups, time factor and interaction (P<0.05). The spatial probe test showed that there were significant between-group differences in comparing the platform crossings and swimming distance in platform quadrant in each age group (P<0.05).Conclusion Electroacupuncture can improve the learning and memory of APP/PS1 double-transgenic mice, the age of 6-7 months old is possibly the optimal intervention time of electroacupuncture for AD, but there still requires further mechanism studies.