Colorectal cancer is one of the most commonly seen malignant tumors,and the metastatic colorectal cancer is of poor prognosis. The median overall survival for chemotherapy is only 1-1. 5 years. Recently,molecular targeted therapy targeting at vascular endothelial growth factor and epidermal growth factor receptor was used widely for metastatic colorectal cancer and becoming a hot spot of related researches. This article focused on the strategy and hypothesis of molecular targeted therapy for treatment of metastatic colorectal cancer.

Objective A scientific evaluation of hospital culture with the Dimension organizational culture model, in view of features of China's general public hospitals.Methods Based on Denison model, according to the characteristics of the public general hospitals in China, the authors developed a tool for organizational culture assessment (TOCA) by using the survey data from 87 hospitals in three provinces from the East, Central, and West areas in China.Results This tool, an evaluation scale, comprises the four cultural characteristics of direction, consistency, participation, and adaptability, as well as 13 cultural dimensions of social responsibility and competitive consciousness. The tool is tested as having good internal reliability and validity.Conclusion The TOCA provides hospital administrators with a tool for hospital culture evaluation, diagnosis and improvement.

Objective To investigate the clinical significance of testing serum kisspeptin in central precocious puberty (CPP) girls. Methods Sixty eight CPP girls and 68 healthy girls was studied from December 2012 to December 2014. HEK293 cells were cultured. Luciferase reporter assay was performed to verify the binding of miR-137 to the 3′UTR of KISS1. Serum miR-137 level was levaluated by qRT-PCR. Level of serum luteinizing hormone , prolactin , follicle stimulating hormone , thyrotropin , free thyroxine and estradiol was evaluated by chemi-luminescence immunoassay. The level of serum kisspeptin was detected by ELISA. Results MiR-137 was confirmed to bind to the 3′UTR of KISS1. The level of serum miR-137 was downregulated and kisspeptin was enhanced in CPP girls. The expression of miR-137 and kisspeptin was negatively correlated. Serum miR-137 level was negatively related to bone age and bone age advancement. According to the results of GnRH stimulating test, serum miR-137 was related to peak LH and peak/basal LH ratio. Conclusions MiR-137 could bind to the 3′UTR of KISS1. MiR-137 may be a potential biomarker for CPP assisted diagnosis.

Objective To summarize the pathogenesis,diagnosis and treatment of aplasia cutis congenita (ACC) in China.Methods We reviewed and summarized all published ACC cases in China in the past four decades from China National Knowledge Internet(CNKI),Wan-Fang Medical Database and VIP database.Results Totally,258 cases were included,consisting of 144 males,95 females and 19 of unknown gender.Fifteen cases reported family history,16 had maternal morbidity during pregnancy,17 exposed to maternal medication or toxic material.Skin lesions of ACC occurred on the scalp (39 cases,15.1％),trunk (8 cases,3.1％) or limbs (107 cases,41.5％) and sometimes were manifested as multiples skin defects (104 cases,40.3％).Eighty-nine cases (38.4％) were presented with isolated skin defect,and 169 (61.6％) were complicated by other abnormalities or congenital defects.Totally,235(91.1％) cases were treated conservatively,15 cases with dural defect,skull defect or defect area ＞ 10％ underwent dermatoplasty,and the other eight cases refused any treatment.Among the 248 cases being followed up,233 (93.95％) healed after treatment for one week to four months,three had scar contracture,four developed joint contracture,and eight (3.2％) died of hemorrhage or infection.Conclusions ACC is a congenital skin defect which might involve skin,bone and multiple parts of the body,often complicated with other abnormalities.Superficial and small skin defect maybe managed conservatively,while for patients with bone exposure or defect,large area skin defect,surgical management is recommended.Appropriate management can ensure good outcomes in most cases.

Objective To investigate the parental stress, social support and quality of life in mothers of children with precocious puberty, and to explore the impact of parental stress and social support on the quality of life.Methods A questionnaire survey of 96 mothers of children with precocious puberty was conducted using the "Family Stress Index", "Social Support Rating Scale" and "World Health Organization Quality of Life Survey (Chinese version)".Results The total score of parental stress and the scores of different dimensions in mothers with precocious puberty were significantly higher than those of normal parents (P<0.01). The total score of social support of mothers with precocious puberty was significantly higher than that of domestic norm (P<0.01). The scores of quality of life of mothers with precocious puberty were significantly lower than those of domestic norm in the field of physiology and psychology (P<0.01). Negative correlation existed not only between parental stress and quality of life, but also between parental stress and social support. Positive correlation existed between social support and quality of life.Conclusions The mothers of children with precocious puberty have high parental pressure, high social support and low quality of life. There are correlations among the three dimensions. Offering health education and mental nursing can improve the compliance during the therapy and the quality of life of both children and family.

Deciphering the metabolites of multiple components in herbal medicine has far-reaching significance for revealing pharmacodynamic ingredients.However,most chemical components of herbal medicine are secondary metabolites with low content whose in vivo metabolites are close to trace amounts,making it difficult to achieve comprehensive detection and identification.In this paper,an efficient strategy was proposed:herb-derived metabolites were predicted according to the structural characteristics and metabolic reactions of chemical constituents in Corydalis Rhizoma and chemical structure screening tables for metabolites were conducted.The fragmentation patterns were summarized from represen-tative standards combining with specific cleavage behaviors to deduce structures of metabolites.Ion abundance plays an important role in compound identification,and high ion abundance can improve identification accuracy.The types of metabolites in different biological samples were very similar,but their ion abundance might be different.Therefore,for trace metabolites in biological samples,we used the following two methods to process:metabolites of high dose herbal extract were analyzed to char-acterize those of clinical dose herbal extracts in the same biological samples;cross-mapping of different biological samples was applied to identify trace metabolites based on the fact that a metabolite has different ion abundance in different biological samples.Compared with not using this strategy,44 more metabolites of clinical dose herbal extract were detected.This study improved the depth,breadth,and accuracy of current methods for herb-derived metabolites characterization.

Objective To investigate the significance of serum adenosine deaminase level in type 1 diabe-tes patients(T1DM)with acute or chronic diabetes complications. Methods One hundred and eighty-four cases of type 1 diabetes patients were divided into three groups:T1DM without any complications(n = 55),T1DM with acute diabetes complications(n = 47)and T1DM with chronic diabetes complications(n = 82). We also enrolled 108 healthy persons as the control group.The clinical and biochemical data were collected and the influencing fac-tors of serum ADA were analyzed. Resultes(1)Serum ADA level of T1DM patients was higher than that of the healthy control people.T1DM patients with acute diabetes complications had lower serum ADA level compared with T1DM patients with chronic complications.(2)Results of Pearson correlations analysis showed that serum ADA level had positive correlation with fasting blood glucose.(3)Logistic regression analysis showed that the increase of serum ADA level was an independent risk factor in patients with chronic diabetes complications(OR:1.159,95% Cl:1.044~1.286),while it was a protective factor in patients with acute diabetes complications(OR:0.857,95% Cl:0.748~0.981). Conclusions High serum ADA level was observed in type 1 diabetes patients. The serum ADA level was an independent risk factor for T1DM patients with chronic diabetes complications,while it was a protective factor for T1DM patients with acute diabetes complications.

Objective:To compare the efficacy and safety of standard treatment with or without adjuvant chemotherapy in patients with highly malignant non-metastatic prostate cancer.Methods:In this prospective non-randomized controlled study, consecutive non-metastatic prostate cancer patients with pathologically proven Gleason score of 9-10 or Gleason score of 5 admitted to Peking University First Hospital were enrolled. Four to six cycles of chemotherapy using docetaxel ± carboplatin regimen were added or not after standard radical therapy. The primary end point was 5-year event-free survival (EFS), and the secondary end points were distant metastasis-free survival (MFS), overall survival (OS), and treatment-related adverse events. The survival curve was drawn by Kaplan-Meier method. The differences between two groups were analyzed by log-rank test.Results:A total of 176 patients were consecutively enrolled from November 2019 to January 2022 of which 138 patients received only standard radical therapy (control group), and 38 patients received adjuvant chemotherapy after standard radical therapy (chemotherapy group). The median follow-up time was 13.4 (2.0-34.0) months. All patients survived. The 30-month EFS rates in the chemotherapy and control groups were 100% and 85.6%, respectively ( P=0.064). There were no events in the chemotherapy group, while there were 12 cases of events in the control group, including 6 cases of biochemical recurrence and 6 cases of imaging progression. The 30-month MFS rates in two groups were 100% and 91.9%, respectively ( P=0.205). After the 1 vs. 2 propensity score matching, the EFS and MFS rates in two groups were 100% vs. 85.7% ( P=0.056), and 100% vs. 92.2% ( P=0.209), respectively. The incidence rates of grade 2 and above urinary toxicity in the chemotherapy and control groups were 2.6% and 7.2% ( P=0.354), respectively. The incidence rates of grade 2 and above rectal toxicity were 5.3% and 5.1% ( P=0.711), respectively. Grade 3 and above chemotherapy-related toxicity in the chemotherapy group were leukopenia (31.6%), thrombocytopenia (2.6%) and alopecia (13.2%). Conclusion:The addition of adjuvant chemotherapy after standard radical therapy tends to improve the overall EFS of patients with highly malignant prostate cancer, and the adverse effects are tolerable, which should be confirmed by long-term follow-up results.

Hepatocellular carcinoma(HCC)is one of the most common tumor types and remains a major clinical challenge.Increasing evidence has revealed that mitophagy inhibitors can enhance the effect of chemotherapy on HCC.However,few mitophagy inhibitors have been approved for clinical use in humans.Pyrimethamine(Pyr)is used to treat infections caused by protozoan parasites.Recent studies have reported that Pyr may be beneficial in the treatment of various tumors.However,its mechanism of action is still not clearly defined.Here,we found that blocking mitophagy sensitized cells to Pyr-induced apoptosis.Mechanistically,Pyr potently induced the accumulation of autophagosomes by inhibiting autophagosome-lysosome fusion in human HCC cells.In vitro and in vivo studies revealed that Pyr blocked autophagosome-lysosome fusion by upregulating BNIP3 to inhibit synaptosomal-associated protein 29(SNAP29)-vesicle-associated membrane protein 8(VAMP8)interaction.Moreover,Pyr acted synergistically with sorafenib(Sora)to induce apoptosis and inhibit HCC proliferation in vitro and in vivo.Pyr enhances the sensitivity of HCC cells to Sora,a common chemotherapeutic,by inhibiting mitophagy.Thus,these results provide new insights into the mechanism of action of Pyr and imply that Pyr could potentially be further developed as a novel mitophagy inhibitor.Notably,Pyr and Sora combination therapy could be a promising treatment for malignant HCC.

Objective To understand the quality of life in patients with pulmonary tuberculosis within three years after treatment， determine its related factors， and make suggestions for improving the short-term quality of life in patients with pulmonary tuberculosis after treatment. Methods A telephone survey was used to investigate registered tuberculosis patients in Shanghai in 2018 using the short form 12 （SF-12） and the chronic obstructive pulmonary disease （COPD） assessment test questionnaire （CAT）. Results A total of 975 patients with pulmonary tuberculosis who had completed the treatment were included in the study. The total physiological score was determined to be 49.18±10.25， and the total psychological score was 50.27±8.03 （t=5.62，P<0.000 1）. The average CAT score was 13.31±6.08. Multivariate linear regression analysis showed that quality of life was positively associated with high educational level， high monthly family income， and frequent physical exercise， whereas negatively associated with comorbidities， low self-care ability， and changing jobs. Conclusion We should pay more attention to the patients with pulmonary tuberculosis coexistent with COPD and other lung diseases. Measures should be implemented for the improvement in the quality of life， including providing financial support， encouraging regular exercise， and improving lung function.