RACGAP1 knockdown synergizes and enhances the effects of chemotherapeutics on ovarian cancer.

Among the three most prevalent cancers affecting the female reproductive system, ovarian cancer (OV) ranks as the second most frequently diagnosed. It is important to investigate the genomic complexity of OV to develop diagnostic and therapeutic strategies. Through the utilization of bioinformatics analysis, it was determined that RacGTPase Activating Protein 1 (RACGAP1) holds significant significance in the field of OV chemotherapeutics, an aspect that has not been thoroughly explored in prior investigations. In our study, a notable increase in RACGAP1 expression was detected in ovarian cancer, demonstrating a robust association with clinicopathological features and patient prognosis. In vivo and in vitro testing revealed that RACGAP1 acts synergistically with chemotherapeutics to enhance their effects on ovarian cancer. Furthermore, an interaction between RACGAP1 and the subunit G2 of the condensin II complex, known as non-SMC condensin II complex subunit G2 (NCAPG2), has been identified. Our findings may provide new insight for improving therapeutic strategies for OV.

Preoperative prognostic nutritional index predicts long-term outcomes of patients with ampullary adenocarcinoma after curative pancreatoduodenectomy.

BACKGROUND: The prognostic nutritional index (PNI), a marker of immune-nutrition balance, has predictive value for the survival and prognosis of patients with various cancers. AIM: To explore the clinical significance of the preoperative PNI on the prognosis of ampullary adenocarcinoma (AC) patients who underwent curative pancreaticoduodenectomy. METHODS: The data concerning 233 patients diagnosed with ACs were extracted and analyzed at our institution from January 1998 to December 2020. All patients were categorized into low and high PNI groups based on the cutoff value determined by receiver operating characteristic curve analysis. We compared disease-free survival (DFS) and overall survival (OS) between these groups and assessed prognostic factors through univariate and multivariate analyses. RESULTS: The optimal cutoff value for the PNI was established at 45.3. Patients with a PNI ≥ 45.3 were categorized into the PNI-high group, while those with a PNI < 45.3 were assigned to the PNI-low group. Patients within the PNI-low group tended to be of advanced age and exhibited higher levels of aspartate transaminase and total bilirubin and a lower creatinine level than were those in the PNI-high group. The 5-year OS rates for patients with a PNI ≥ 45.3 and a PNI < 45.3 were 61.8% and 43.4%, respectively, while the 5-year DFS rates were 53.5% and 38.3%, respectively. Patients in the PNI- low group had shorter OS (P = 0.006) and DFS (P = 0.012). In addition, multivariate analysis revealed that the PNI, pathological T stage and pathological N stage were found to be independent prognostic factors for both OS and DFS. CONCLUSION: The PNI is a straightforward and valuable marker for predicting long-term survival after pancreatoduodenectomy. The PNI should be incorporated into the standard assessment of patients with AC.

Machine learning developed a CD8+ exhausted T cells signature for predicting prognosis, immune infiltration and drug sensitivity in ovarian cancer.

CD8+ exhausted T cells (CD8+ Tex) played a vital role in the progression and therapeutic response of cancer. However, few studies have fully clarified the characters of CD8+ Tex related genes in ovarian cancer (OC). The CD8+ Tex related prognostic signature (TRPS) was constructed with integrative machine learning procedure including 10 methods using TCGA, GSE14764, GSE26193, GSE26712, GSE63885 and GSE140082 dataset. Several immunotherapy benefits indicators, including Tumor Immune Dysfunction and Exclusion (TIDE) score, immunophenoscore (IPS), TMB score and tumor escape score, were used to explore performance of TRPS in predicting immunotherapy benefits of OC. The TRPS constructed by Enet (alpha = 0.3) method acted as an independent risk factor for OC and showed stable and powerful performance in predicting clinical outcome of patients. The C-index of the TRPS was higher than that of tumor grade, clinical stage, and many developed signatures. Low TRPS score indicated a higher level of CD8+ T cell, B cell, macrophage M1, and NK cells, representing a relative immunoactivated ecosystem in OC. OC patients with low risk score had a higher PD1&CTLA4 immunophenoscore, higher TMB score, lower TIDE score and lower tumor escape score, suggesting a better immunotherapy response. Moreover, higher TRPS score indicated a higher score of cancer-related hallmarks, including angiogenesis, EMT, hypoxia, glycolysis, and notch signaling. Vitro experiment showed that ARL6IP5 was downregulated in OC tissues and inhibited tumor cell proliferation. The current study constructed a novel TRPS for OC, which could serve as an indicator for predicting the prognosis, immune infiltration and immunotherapy benefits for OC patients.

Global, regional, and national burdens of early onset pancreatic cancer in adolescents and adults aged 15-49 years from 1990 to 2019 based on the Global Burden of Disease Study 2019: a cross-sectional study.

BACKGROUND: Early-onset pancreatic cancer (EOPC) in younger populations (age ≤50 years) is likely to be a more aggressive phenotype characterized by poor differentiation. The emerging analysis of the global burden of EOPC is limited and outdated. AIM: To systematically investigate the burden and trend of EOPC based on global populations. METHODS: In this systematic analysis based on the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019, the authors present the number of cases, age-standardized rates (ASRs) per 100 000 population, and risk factors for 204 countries and territories. The average annual percentage changes (AAPCs) for the incidence, mortality, and disability-adjusted life-years (DALYs) of EOPC were calculated using joinpoint regression analysis. RESULTS: According to the GBD 2019 estimates, there were 36 852 new cases of EOPC and 32 004 related deaths. East Asia had the highest number of cases, with 11 401 incidences and 10 149 deaths. The ASRs were 0.94 per 100 000 individuals for incidence and 0.81 per 100 000 for mortality. From 1990 to 2019, the age-standardized incidence increased by 46.9%, mortality increased by 44.6%, and DALYs increased by 41.9% globally. In trend analysis, the global incidence (AAPC, 1.26), mortality (AAPC, 1.24), and DALYs (AAPC, 1.25) of EOPC showed an increasing pattern. The ASRs of incidence, mortality, and DALYs of EOPC in Africa, America, and Asia exhibited a continuous upward trend, while the trend in Europe was fluctuating. Asian males exhibited the fastest growth in incidence (AAPC, 2.15) and mortality (AAPC, 2.13), whereas males in the Americas experienced the slowest increase in new cases (AAPC, 0.72) and deaths (AAPC, 0.67). A certain proportion of EOPC DALYs were attributable to known risk factors: tobacco smoking (13.3%), high BMI, 5.6%, and high fasting plasma glucose 3.2%. Integrating the socio-demographic index (SDI), ASRs of incidence and mortality initially increased with rising SDI, reaching a peak in central Europe (1.5 per 100 000

Analysis of textbook outcomes for ampullary carcinoma patients following pancreaticoduodenectomy.

BACKGROUND: Textbook outcomes (TOs) have been used to assess the quality of surgical treatment for many digestive tumours but not ampullary carcinoma (AC). AIM: To discuss the factors associated with achieving a TO and further explore the prognostic value of a TO for AC patients undergoing curative pancreaticoduodenectomy (PD). METHODS: Patients who underwent PD at the China National Cancer Center between 1998 and 2020 were identified. A TO was defined by R0 resection, examination of ≥ 12 Lymph nodes, no prolonged hospitalization, no intensive care unit treatment, no postoperative complications, and no 30-day readmission or mortality. Cox regression analysis was used to identify the prognostic value of a TO for overall survival (OS) and recurrence-free survival (RFS). Logistic regression was used to identify predictors of a TO. The rate of a TO and of each indicator were compared in patients who underwent surgery before and after 2010. RESULTS: Ultimately, only 24.3% of 272 AC patients achieved a TO. A TO was independently associated with improved OS [hazard ratio (HR): 0.443, 95% confidence interval (95%CI): 0.276-0.711, P = 0.001] and RFS (HR: 0.379, 95%CI: 0.228-0.629, P < 0.001) in the Cox regression analysis. Factors independently associated with a TO included a year of surgery between 2010 and 2020 (OR: 4.549, 95%CI: 2.064-10.028, P < 0.001) and N1 stage disease (OR: 2.251, 95%CI: 1.023-4.954, P = 0.044). In addition, the TO rate was significantly higher in patients who underwent surgery after 2010 (P < 0.001) than in those who underwent surgery before 2010. CONCLUSION: Only approximately a quarter (24.3%) of AC patients achieved a TO following PD. A TO was independently related to favourable oncological outcomes in AC and should be considered as an outcome measure for the quality of surgery. Further multicentre research is warranted to better elucidate its impact.

Novel prognostic score based on the preoperative total bilirubin-albumin ratio and fibrinogen-albumin ratio in ampullary adenocarcinoma.

BACKGROUND: The preoperative total bilirubin-albumin ratio (TBAR) and fibrinogen-albumin ratio (FAR) have been proven to be valuable prognostic factors in various cancers. AIM: To detect the prognostic value of TBAR and FAR in ampullary adenocarcinoma (AC) patients who underwent curative pancreaticoduodenectomy. METHODS: AC patients who underwent curative pancreaticoduodenectomy in the National Cancer Center of China between 1998 and 2020 were retrospectively reviewed. The prognostic cutoff values of TBAR and FAR were determined through the best survival separation model. Then, a novel prognostic score combining TBAR and FAR was calculated and validated through the logistic regression analysis and Cox regression analysis. RESULTS: A total of 188 AC patients were enrolled in the current study. The best cutoff values of TBAR and FAR for predicting overall survival were 1.7943 and 0.1329, respectively. AC patients were divided into a TBAR-low group (score = 0) vs a TBAR-high group (score = 1) and a FAR-low group (score = 0) vs a FAR-high group (score = 1). The total score was calculated as a novel prognostic factor. Multivariable logistic regression analysis revealed that a high score was an independent protective factor for recurrence [score = 1 vs score = 0: Odds ratio (OR) = 0.517, P = 0.046; score = 2 vs score = 0 OR = 0.236, P = 0.038]. In addition, multivariable survival analysis also demonstrated that a high score was an independent protective factor in AC patients (score = 2 vs score = 0: Hazard ratio = 0.230, P = 0.046). CONCLUSION: A novel prognostic score based on preoperative TBAR and FAR has been demonstrated to have good predictive power in AC patients who underwent curative pancreaticoduodenectomy. However, more studies with larger samples are needed to validate this conclusion.

Equivalent Survival between Gastric Large-Cell Neuroendocrine Carcinoma and Gastric Small-Cell Neuroendocrine Carcinoma.

BACKGROUND: According to the 2019 World Health Organization (WHO) classification of gastric neuroendocrine neoplasms, gastric neuroendocrine carcinoma (GNEC) can be further divided into gastric large-cell neuroendocrine carcinoma (GLNEC) and gastric small-cell neuroendocrine carcinoma (GSNEC). Whether the prognoses of the two types have a discrepancy has long been disputed. METHOD: We collected patients diagnosed with GLNEC or GSNEC in the National Cancer Center of China between January 2000 and December 2020. The characteristics and survival outcomes were compared between the two groups. We further verified our conclusion using the SEER dataset. RESULTS: A total of 114 GNEC patients, including 82 patients with GLNEC and 32 patients with GSNEC, have completed treatment in our hospital. Clinicopathologic differences were not observed between patients with GSNEC and GLNEC concerning the sex, age, body mass index, Charlson Comorbidity Index, tumor location, tumor size, stage, treatment received, the expression of neuroendocrine markers (CD56, Chromogranin A, synaptophysin), and score on the Ki-67 index. The 1-year, 3-year, and 5-year overall survival rates of GLNEC and GSNEC were 89.0%, 60.5%, and 52.4%, and 93.8%, 56.3%, and 52.7%, which showed no statistically significant differences. This result was confirmed further by using the SEER dataset after the inverse probability of treatment weighting. CONCLUSIONS: Although with different cell morphology, the comparison of prognosis between the GLNEC and GSNEC has no significant statistical difference.

Hepatoid adenocarcinoma of the stomach with neuroendocrine differentiation: A case report and review of literature.

BACKGROUND: Both hepatoid adenocarcinoma of the stomach (HAS) and neuroendocrine differentiation (NED) are rare histological subtypes of gastric cancer with unique clinicopathological features and unfavorable outcomes. HAS with NED is even rarer. CASE SUMMARY: Here, we report a 61-year-old man with HAS with NED, as detected by gastric wall thickening by positron emission tomography/computed tomography for a pulmonary nodule. Distal gastrectomy was performed, and pathological examination led to the diagnosis of HAS with NED. However, liver metastases occurred 6 mo later despite adjuvant chemotherapy, and the patient died 27 mo postoperatively. CONCLUSION: We treated a patient with HAS with NED who underwent adjuvant chemotherapy after radical surgery and still developed liver metastases. We first report the detailed processes of the treatment and development of HAS with NED, providing an important reference for the clinical diagnosis and treatment of this condition.

Impact of perioperative blood transfusion on oncological outcomes in ampullary carcinoma patients underwent pancreaticoduodenectomy.

BACKGROUND: The effect of perioperative blood transfusion (PBT) on the prognosis of ampullary carcinoma (AC) is still debated. AIM: To explore the impact of PBT on short-term safety and long-term survival in AC patients who underwent pancreaticoduodenectomy. METHODS: A total of 257 patients with AC who underwent pancreaticoduodenectomy between 1998 and 2020 in the Cancer Hospital, Chinese Academy of Medical Sciences, were retrospectively analyzed. We used Cox proportional hazard regression to identify prognostic factors of overall survival (OS) and recurrence-free survival (RFS) and the Kaplan-Meier method to analyze survival information. RESULTS: A total of 144 (56%) of 257 patients received PBT. The PBT group and nonperioperative blood transfusion group showed no significant differences in demographics. Patients who received transfusion had a comparable incidence of postoperative complications with patients who did not. Univariable and multivariable Cox proportional hazard regression analyses indicated that transfusion was not an independent predictor of OS or RFS. We performed Kaplan-Meier analysis according to subgroups of T stage, and subgroup analysis indicated that PBT might be associated with worse OS (P < 0.05) but not RFS in AC of stage T1. CONCLUSION: We found that PBT might be associated with decreased OS in early AC, but more validation is needed. The reasonable use of transfusion might be helpful to improve OS.

Dissimilar survival and clinicopathological characteristics of mucinous adenocarcinoma located in pancreatic head and body/tail.

BACKGROUND: Growing evidence shows that pancreatic tumors in different anatomical locations have different characteristics, which have a significant impact on prognosis. However, no study has reported the differences between pancreatic mucinous adenocarcinoma (PMAC) in the head vs the body/tail of the pancreas. AIM: To investigate the differences in survival and clinicopathological characteristics between PMAC in the head and body/tail of pancreas. METHODS: A total of 2058 PMAC patients from the Surveillance, Epidemiology, and End Results database diagnosed between 1992 and 2017 were retrospectively reviewed. We divided the patients who met the inclusion criteria into pancreatic head group (PHG) and pancreatic body/tail group (PBTG). The relationship between two groups and risk of invasive factors was identified using logistic regression analysis. Kaplan-Meier analysis and Cox regression analysis were conducted to compare the overall survival (OS) and cancer-specific survival (CSS) of two patient groups. RESULTS: In total, 271 PMAC patients were included in the study. The 1-year, 3-year, and 5-year OS rates of these patients were 51.6%, 23.5%, and 13.6%, respectively. The 1-year, 3-year, and 5-year CSS rates were 53.2%, 26.2%, and 17.4%, respectively. The median OS of PHG patients was longer than that of PBTG patients (18 vs 7.5 mo, P < 0.001). Compared to PHG patients, PBTG patients had a greater risk of metastases [odds ratio (OR) = 2.747, 95% confidence interval (CI): 1.628-4.636, P < 0.001] and higher staging (OR = 3.204, 95% CI: 1.895-5.415, P < 0.001). Survival analysis revealed that age < 65 years, male sex, low grade (G1-G2), low stage, systemic therapy, and PMAC located at the pancreatic head led to longer OS and CSS (all P < 0.05). The location of PMAC was an independent prognostic factor for CSS [hazard ratio (HR) = 0.7, 95%CI: 0.52-0.94, P = 0.017]. Further analysis demonstrated that OS and CSS of PHG were significantly better than PBTG in advanced stage (stage III-IV). CONCLUSION: Compared to the pancreatic body/tail, PMAC located in the pancreatic head has better survival and favorable clinicopathological characteristics.

Exploration of the lymphadenectomy strategy for elderly pancreatic ductal adenocarcinoma patients undergoing curative-intent resection.

There has been a long-standing controversy regarding the number of lymph nodes (LNs) examined intraoperatively for accurate lymphatic staging and significantly better survival of patients with pancreatic ductal adenocarcinoma (PDAC), and no consensus has been reached for the elderly with the age of over 75 years. Given these, the present study aims to investigate the appropriate number of examined lymph nodes (ELNs) for elderly patients mentioned above. In this study, population-based data on 20,125 patients in 2000 to 2019 from the Surveillance, Epidemiology, and End Results database were reviewed retrospectively. The eighth edition staging system of the American Joint Committee on Cancer (AJCC) was applied. Propensity score matching (PSM) was performed to reduce the effects of multiple biases. By using binomial probability law and maximally selected rank statistics, the minimum number of ELN (MNELN) for accurate nodal involvement assessment and optimal ELN number for significantly better survival were calculated, respectively. In addition, Kaplan-Meier curves and Cox proportional hazard regression models were constructed for further survival analysis. As a result, 6623 patients were enrolled in total in the study. Elderly patients had fewer lymph node metastases and a smaller lymph node ratio (LNR) (all P<0.05). However, poorer overall survival (OS) and cancer-specific survival (CSS) of elderly patients were observed in each pN stage (all P<0.05), except for CSS in N2. The proportions of N2 and N0 stages increased and decreased respectively with increasing number of ELN significantly. MNELN for accurate nodal assessment was 19 according to binomial probability law, and the optimal ELN number for significantly better survival was 17. Additionally, the number of ELN (<17 or ≥17) was also considered a strong prognostic predictor for elderly PDAC patients (≥75 years) in the Cox proportional hazard regression model (Overall survival: hazard ratio [HR]=0.74, 95% confidence interval [CI]: 0.65-0.83, P<0.001; Cancer-specific survival: HR=0.75, 95% CI: 0.66-0.85, P<0.001). In conclusion, extended lymphadenectomy is suitable for elderly PDAC patients undergoing curative-intent surgery owing to an accurate assessment of nodal status and improved long-term prognosis. However, a random, prospective clinical trial is warranted before the recommendation of extended lymphadenectomy for the elderly.

At least 16 lymph nodes are recommended to examine during pancreaticoduodenectomy in ampullary adenocarcinoma.

The minimum number of lymph nodes to be examined during pancreaticoduodenectomy (PD) for patients with ampullary adenocarcinoma (AC) is still debatable due to limited clinical data. Therefore, here we explored the relationship between the number of examined lymph node (ELN) and the current N staging (American Joint Committee on Cancer staging system, AJCC, 8 edition) after PD for AC as well as determined the minimum number of examined lymph nodes (MNELN) to ensure the accurate detection of nodal involvement. Patients underwent PD for AC in the National Cancer Center cohort of China (NCC cohort of China) from 1998 to 2020 and in the Surveillance, Epidemiology, and End Results database (SEER database) from 2010 to 2018 were retrospectively reviewed, and a total of 452 eligible patients were included in this study. The MNELN was evaluated by binomial probability law and best survival separation methods. Furthermore, the cut-off value of MNELN was validated in the NCC cohort of China using Least Absolute Shrinkage and Selection Operator (LASSO) regression. Our analysis indicated that the median number of ELN was 14, and the number of ELN was positively correlated with N stage. The MNELN was 16, whereas the best survival separation of ELN was 38 in node-positive patients and 3 in node-negative patients. In the validation cohort, the number of 16 ELNs was identified as a predictive variable for lymph node metastasis with nonzero coefficients in the LASSO-logistic regression model. Together, we concluded that a greater number of ELN was associated with more accurate nodal status assessment in PD for AC patients. A minimum of 16 lymph nodes were required to during PD in AC patients.

CD93 serves as a potential biomarker of gastric cancer and correlates with the tumor microenvironment.

BACKGROUND: The tumor microenvironment (TME) plays an important role in the growth and expansion of gastric cancer (GC). Studies have identified that CD93 is involved in abnormal tumor angiogenesis, which may be related to the regulation of the TME. AIM: To determine the role of CD93 in GC. METHODS: Transcriptomic data of GC was investigated in a cohort from The Cancer Genome Atlas. Additionally, RNA-seq data sets from Gene Expression Omnibus (GSE118916, GSE52138, GSE79973, GSE19826, and GSE84433) were applied to validate the results. We performed the immune infiltration analyses using ESTIMATE, CIBERSORT, and ssGSEA. Furthermore, weighted gene co-expression network analysis (WGCNA) was conducted to identify the immune-related genes. RESULTS: Compared to normal tissues, CD93 significantly enriched in tumor tissues (t = 4.669, 95%CI: 0.342-0.863, P < 0.001). Higher expression of CD93 was significantly associated with shorter overall survival (hazard ratio = 1.62, 95%CI: 1.09-2.4, P = 0.017), less proportion of CD8 T and activated natural killer cells in the TME (P < 0.05), and lower tumor mutation burden (t = 4.131, 95%CI: 0.721-0.256, P < 0.001). Genes co-expressed with CD93 were mainly enriched in angiogenesis. Moreover, 11 genes were identified with a strong relationship between CD93 and the immune microenvironment using WGCNA. CONCLUSION: CD93 is a novel prognostic and diagnostic biomarker for GC, that is closely related to the immune infiltration in the TME. Although this retrospective study was a comprehensive analysis, the prospective cohort studies are preferred to further confirm these conclusions.

Does Surgical Resection Significantly Prolong the Long-Term Survival of Patients with Oligometastatic Pancreatic Ductal Adenocarcinoma? A Cross-Sectional Study Based on 18 Registries.

Background: Pancreatic ductal adenocarcinoma (PDAC) is a type of lethal gastrointestinal malignancy. It is mainly discovered at, and diagnosed with, an advanced stage of metastasis. As the only potentially curative treatment for PDAC, surgical resection has an uncertain impact on the survival of these patients. As such, we aimed to investigate if patients with metastatic PDAC (mPDAC) benefit from surgery. Methods: Patients with pancreatic cancer in 18 registries of the Surveillance, Epidemiology, and End Results database between 2000 and 2018 were reviewed retrospectively. According to the American Joint Committee on Cancer (AJCC), the eighth edition staging system was utilized. Propensity score matching was applied to strengthen the comparability of the study. The impact of surgery on survival was evaluated by restricted mean survival time (RMST) and Kaplan−Meier analysis. Results: A total of 210 well-matched mPDAC patients were included in the study. The 1 year, 3 year, and 5 year overall survival (OS) of patients undergoing surgery was 34.3%, 15.2%, and 11.0%, respectively. The 1 year, 3 year, and 5 year cancer-specific survival (CSS) of these patients was 36.1%, 19.7%, and 14.2%, respectively. RMST analysis revealed that mPDAC patients with surgery had better OS and CSS than those without (OS: 9.49 months vs. 6.45 months, p < 0.01; CSS: 9.76 months vs. 6.54 months, p < 0.01). Nevertheless, subgroup analysis demonstrated that such statistical significance especially existed in oligometastatic PDAC patients, which refers to those metastases that were limited in number and concentrated to a single organ in this study. Additionally, surgery was identified as a significant predictor for the long-term prognosis of patients (OS: [HR, hazard ratio] = 0.48, 95% CI: 0.36−0.65, p < 0.001; CSS: HR = 0.45, 95% CI: 0.33−0.63, p < 0.001). Lastly, a nomogram was established to predict whether an individual was suitable for surgical treatment in this study. Conclusions: Surgical resection significantly prolonged the long-term prognosis of oligometastatic PDAC patients. Such insights might broaden the management of patients with mPDAC to a large extent. However, a prospective clinical trial should be conducted before a recommendation of surgery in these patients.

Research progress on genome-guided precision oncology and development ideas of antitumor Chinese medicine / 中国中药杂志

Genome-guided oncology refers to a new treatment concept that transcends histological classification and pathological ty-ping and uses drugs according to the genetic characteristics of tumors. New drug development technology and clinical trial design based on this concept provide new ideas for the clinical application of precision oncology. The multi-component and multi-target characteristics of Chinese medicine provide rich resources for the development of tumor-targeting drugs from natural products, and the design of the master protocol trial aiming at the characteristics of precision oncology supports the rapid clinical screening of effective tumor-targeting drugs. The emergence of the synthetic lethality strategy breaks through the bottleneck that the drug can only target the oncogene but cannot do anything to the tumor suppressor gene with the loss-of-function mutation in the past. With the rapid development of high-throughput sequencing technology, the cost of sequencing is also decreasing. For the development of tumor-targeting drugs, how to keep up with the update speed of target information is a difficult problem of concern. Based on the integration of innovative ideas and me-thods of precision oncology, network pharmacology, and synthetic lethality strategy on synthetic lethal interaction network of antitumor Chinese medicine compatibility formula design, and the combination of improvement of innovative clinical trial methods, such as master protocol trial, basket trial, and umbrella trial, unique advantages of Chinese medicine are expected to be exerted beyond the antibody-based drugs and small molecule-based drugs and corresponding targeted drugs are potentially developed for clinical application.

Prevalence and incidence of heart failure among community in China during a three-year follow-up / 老年心脏病学杂志（英文版）

BACKGROUND@#Epidemiological surveys on heart failure (HF) in Chinese community are relatively lacking. This study aimed to estimate the prevalence and incidence of HF among community residents in southern China.@*METHODS@#Baseline data of this prospective study was collected from 2015 to 2017 among 12,013 permanent residents aged ≥ 35 years in Guangzhou, China. The same survey process was carried out for individuals aged ≥ 65 years after a three-year follow-up.@*RESULTS@#The overall prevalence of HF in community residents aged ≥ 35 years was 1.06%. Male had significantly higher risk of HF prevalence [odds ratio (OR) = 1.50, P = 0.027]. The gender-adjusted risk of HF was 1.48 times higher per 10 years aging. HF prevalence was statistically associated with atrial fibrillation, valvular heart disease, hypertension and chronic obstructive pulmonary disease after adjusting for age and gender (OR = 8.30, 5.17, 1.11, 2.28, respectively; all P < 0.05). HF incidence in individuals aged ≥ 65 years were 847 per 100,000 person-years. Baseline atrial fibrillation, valvular heart disease, and diabetes mellitus were risk factors for HF incidence for individuals aged ≥ 65 years adjusting for age and gender (OR = 5.05, 3.99, 2.11, respectively; all P < 0.05). Besides, residents with new-onset atrial fibrillation and myocardial infarction were at significantly higher risk of progression to HF (OR = 14.41, 8.54, respectively; all P < 0.05).@*CONCLUSIONS@#Both pre-existing and new-onset cardiovascular diseases were associated with HF incidence in southern China. Management of related cardiovascular diseases may be helpful to reduce the incidence of HF.

Study on the fingerprint of total saponins from Mussaenda pubescens and the spectrum-effect relationship of its hepatoprotective activity / 中国药房

OBJECTIVE To establish the fingerprint of total saponins from Mussaenda pubescens， and to study the spectrum- effect relationship of its hepatoprotective activity. METHODS Ten batches of total saponins from M. pubescens from different origins were prepared using 75% ethanol as solvent. High-performance liquid chromatography （HPLC） and the Similarity Evaluation System for Traditional Chinese Medicine Chromatographic Fingerprints （2012 edition） were used to draw the fingerprints of 10 batches of total saponins from M. pubescens. The similarity evaluation and identification of common peaks were conducted. The same HPLC method was adopted to determine the contents of five triterpenoid saponins （mussaendoside H， mussaendoside U， mussaglaoside C， mussaendoside G and mussaendoside O）. The hepatoprotective effect of total saponins from M. pubescens was investigated by establishing carbon tetrachloride-induced acute liver injury model mice， and the spectrum-effect relationship was studied by using grey correlation analysis. RESULTS There were 11 common peaks in 10 batches of total saponins from M. pubescens， 5 of which were identified， i.e. mussaendoside H （peak 3）， mussaendoside U （peak 7）， mussaglaoside C （peak 8）， mussaendoside G （peak 9） and mussaendoside O （peak 11）； the similarities of 10 batches of samples ranged 0.940- 0.991. Average contents of mussaendoside H， mussaendoside U， mussaglaoside C， mussaendoside G， mussaendoside O were 0.01- 0.05， 0.10-0.21， 0.10-0.18， 0.03-0.08， 0.20-0.40 mg/g， respectively. Ten batches of total saponins from M. pubescens could generally reduce the contents of alanine aminotransferase （ALT） and aspartate aminotransferase （AST） in serum， and tumor necrosis factor-α （TNF-α）， interleukin-6 （IL-6） and IL-1β in liver tissue of model mice （P＜0.05 or P＜0.01）. The E-mail：13878195336@139.com correlation between the common peak areas and the contents of ALT， AST， TNF-α， IL-6 and IL-1β were 0.602-0.757， 0.585-0.833， 0.593-0.795， 0.618-0.820， 0.607-0.804， respectively； the peaks with high correlation were peaks 11， 9 and 8 in order. CONCLUSIONS Ten batches of total saponins from M. pubescens have similar components， and the average contents of mussaendoside H， mussaendoside U， mussaglaoside C， mussaendoside G and mussaendoside O are different. The batches of samples have a certain degree of hepatoprotective effect； mussaendoside O， mussaendoside G and mussaglaoside C may be its main active components.

Efficacy and safety of percutaneous left atrial appendage occlusion for nonvalvular atrial fibrillation / 中国基层医药

Objective:To investigate the efficacy and safety of percutaneous left atrial appendage occlusion in the treatment of nonvalvular atrial fibrillation.Methods:Eighty-eight patients with percutaneous left nonvalvular atrial fibrillation who received treatment in The Second Hospital of Anhui Medical University from January 2019 to January 2021 were included in this study. These patients were divided into three groups according to different anticoagulant methods: group A (percutaneous left atrial appendage occlusion), group B (livaraban), and group C (warfarin). The incidence of stroke, the incidence of bleeding events, the incidence of adverse cardiovascular events, and live and kidney function and coagulation function after 3 months of treatment were compared among the three groups.Results:There were no significant differences in the incidence of stroke and adverse cardiovascular events among the three groups ( P > 0.05). The incidence of bleeding events in groups A, B, and C was 9.3% (3/32), 15.0% (6/40), and 31.2% (5/16), respectively. There was a significant difference in the incidence of bleeding events among the three groups ( χ2 = 8.07, P = 0.001). After 3 months of treatment, there were no significant differences in prothrombin time, fibrinogen, prothrombin time-international normalized ratio, alanine aminotransferase, aspartate transaminase, and creatinine clearance among the three groups (all P > 0.05). Conclusion:Percutaneous left atrial appendage occlusion, warfarin, and rivaroxaban can prevent stroke in patients with nonvalvular atrial fibrillation. Percutaneous left atrial appendage occlusion is safer and more feasible than warfarin and rivaroxaban alone in the treatment of nonvalvular atrial fibrillation.

Prognostic value of Pitt bacteremia score in patients with extensively drug-resistant Klebsiella pneumoniae bloodstream infection / 中华急诊医学杂志

Objective:To investigate the predictive value of Pitt bacteremia score (PBS) on 28-day mortality of patients with extensively drug-resistant Klebsiella pneumoniae (XDR-KP) bloodstream infection.Methods:A retrospective cohort study was conducted to analyze the clinical characteristics of patients with XDR-KP bloodstream infection admitted to the Emergency Intensive Care Unit of Nanjing Drum Tower Hospital from January, 2018, to December, 2021. The patients were divided into the survival and non-survival groups according to the 28-day survival. Multivariate logistic regression analysis was performed to determine the risk factors of 28-day mortality of the patients. Receiver operating curve (ROC) curve was drawn to analyze the predictive value of PBS in 28-day mortality of patients with XDR-KP bloodstream infection. The correlations between PBS, and acute physiology and chronic health evaluation II (APACHE II) and sequential organ failure (SOFA) assessment were performed using Pearson correlation coefficient. The optimal cut-off value of PBS score was used as the boundary point to group the differences between APACHE II and SOFA scores in different groups. Kaplan-Meier method was used to analyze the prognosis of patients with XDR-KP bloodstream infection.Results:A total of 118 patients (82 males and 36 females) with XDR-KP bloodstream infection, aged (65.98±15.16) years, were included in this study. The 28-day mortality was 61.02%. The PBS was significant higher in the non-survival group than in the survival group [(5.68±1.86) vs. (2.48±1.02), P=0.011]. Multivariate logistic regression analysis showed that PBS ( OR=4.940, 95% CI: 2.720-8.968, P=0.008), APACHE II score ( OR=1.630, 95% CI: 1.361-1.952, P=0.010) and SOFA score ( OR=1.879, 95% CI: 1.451-2.422, P=0.009) were independently risk factors of 28-day mortality of patients with XDR-KP bloodstream infection. The area under the ROC curve of the PBS predicting 28-day mortality was 0.970 (95% CI: 0.945-0.995, P<0.001), and the optimal cut-of value was 3.5. In addition, PBS was significantly associated with APACHE II score ( r=0.916, P<0.001) and SOFA score ( r=0.829, P<0.001). Moreover, Kaplan-Meier analysis showed that the 28-day survival rate of patients with PBS <3.5 was significantly higher than that of patients with PBS >3.5 ( P=0.001). Conclusions:PBS is a significant, independent predictor of 28-day mortality in patients with XDR-KP bloodstream infection.

Epidemiological characteristics of varicella in Yandu District from 2005 to 2021 / 预防医学

Objective@#To investigate the epidemiological characteristics of varicella in Yandu District, Yancheng City, Jiangsu Province from 2005 to 2021, so as to provide insights into the improvements of the varicella control strategy.@*Methods@#The data pertaining to cases in Yandu District from 2005 to 2021 were captured from the National Notifiable Diseases Network Reporting System, and the coverage of varicella vaccination in Yandu District from 2016 to 2021 was captured from the Jiangsu Provincial Immunization Planning System. The trends in incidence of varicella were analyzed using annual percent change (APC), the temporal, population and spatial distributions of varicella cases were descriptively analyzed, and the correlation between the cumulative first-dose varicella vaccination rate and incidence of varicella was examined among birth cohorts in Yandu District from 2005 to 2021.@*Results@#Totally 6 144 varicella cases were reported in Yandu District from 2005 to 2021, with annual mean reported incidence of 50.05/105. The incidence of varicella appeared a tendency towards a rise in Yandu District from 2012 to 2018, with APC of 77.97% (t=11.702, P<0.001), and the incidence appeared a tendency towards a decline from 2018 to 2021, with APC of -41.93% (t=-6.911, P<0.001). The incidence of varicella peaked during the period between November and January of the following year (45.95%), and during the period between May and June (20.35%). The mean incidence of varicella was higher among men than among women (54.72/105 vs. 45.00/105; χ2=57.858, P<0.001). The highest incidence of varicella was found among cases at ages of 6 to 9 years (543.78/105), and varicella predominantly occurred among primary school students (38.40%) and pre-school children (31.85%), with high annual mean incidence in the eastern urban areas (74.27/105).The cumulative first-dose varicella vaccination rate negatively correlated with the incidence of varicella among the birth cohorts in Yandu District in 2019 (r=-0.501, P<0.001), 2020 (r=-0.646, P<0.001) and 2021 (r=-0.602, P<0.001).@*Conclusions@#The incidence of varicella appeared a tendency towards a rise followed by a reduction in Yandu District from 2005 to 2021, and the incidence of varicella peaked in winter and at the turn from spring to summer, with varicella predominantly found among primary school students and preschool children.