To introduce the approaches and procedures of neurologic erectile dysfunction (ED ) assessm ent in our institute, and evaluate the neurologic investigation by m aking an analysis of 58 cases. D iagnostic criteria of neurologic ED: nervous system injuries or diseases, abnorm al clinical sym ptom s and signs, electrophysiological abnorm alities of nervous system , abnorm al results of nocturnal penile tum escence and rigidity (N PTR ) (penis rigidity <60% and lasting tim e <10 m inutes). In the group of 20 patients w ith the injuries of the brain, spinal cord or spinal root nerves, pudendal cortical som atic evoked potential (PCSEP), sacral reflex latency (SRL),pudendal-to-corticalm otorevoked potential (PCM EP), penile sym-pathetic skin responses (PSSR ) and N PTR show ed abnorm ality by 45%, 20%, 20%, 85% and 85%, re-spectively. In 38 patients w ith the injuries of pelvic fracture w ith urethra break, PCSEP, SRL, PCM EP, PSSR and N PTR show ed abnorm ality by 24% , 5% , 20% , 92% and 66% , respectively. In the form er, 35% w ere identified to have severe ED , and 50%, m oderate ED;in the latter, 21%, to have severe ED , 13%, m edium ED , and 37%, light ED . The approaches and procedures w ere proved to possess excellent specificity and reliability in the assessm ent of neurological ED .

BACKGROUND: There are few studies conceming morphological charactedstics, space-time distribution and differentiation of hepatic stem cells during embryo liver development.OBJECTIVE: To understand the action of alpha fetoprotein, cytokeratin-19 (CK19) and c-Met in the liver through observing the expression of them.DESIGN, TIME AND SETTING: The in vitro cytological observational study was performed at the Central Laboratory of Weifang Medical College from June 2005 to December 2006.MATERIALS: A total of 40 embryo samples were obtained from 3-rnonth aborted fetus, which were supplied by Hospital Affiliated to Weifang Medical College.METHODS: Aborted embryo was collected and made into sections within 30 minutes. Fetal age was defined according to embryonic layer formation, somite number and organ development under a microscope. Sample sections with fetal age of 3-12weeks were selected. One was collected from every eleven sections and underwent immunohistochemical staining.MAIN OUTCOME MEASURES: Expression of alpha fetoprotein, CK19 and c-Met was measured in embryo hepatic stem cells aged 3-12 weeks.RESULTS: At 3-5 weeks, samples were positive for alpha fetoprotein and c-Met, which were indicated as hepatic stem ceils. At 10-12 weeks, alpha fetoprotein- and c-Met-positive cells were mainly distributed surrounding the header, which suggested that hepatic stem cells were mainly located at hepatic cord of the header. This had similar distribution as adult hepatic oval cells (adult hepatic stem cells). CK19-positive reaction was found at week 7, and mainly at hepatic cord cells, bile duct sheet cells and bile duct epithelial cells at 10-11 weeks. CKlg-positive reaction was only seen at the bile duct sheet and bile duct epithelial cells at week 12. At this time, all bile duct sheet cells and bile duct epithelial cells were positive for alpha fetoprotein, c-Met and CK19.CONCLUSION: CK19-positive reaction was not found in hepatic stem cells, but only detected in bile duct epithelial cells and progenitor calls. CK19 may be not fit for a marker of hepatic stem cells. All bile duct sheet and bile duct epithelial cells are positive for alpha fetoprotein, c-Met and CK19. It is assumed that alpha fetoprotein+/c-Met+/CK19+ may be bile duct progenitor calls.

Objective:To investigate the clinical characteristics and prognosis of Philadelphia (Ph) chromosome-positive chronic myeloid leukemia (CML) patients with additional chromosomal abnormalities.Methods:The data of 351 CML patients with Ph-positive in the Affiliated Hospital of Qingdao University from January 2009 to January 2019 were retrospectively analyzed. The bone marrow chromosomal karyotype analysis of all patients was performed by using R-banding technique. The clinical characteristics and karyotype of Ph-positive CML patients with additional chromosomal abnormalities at initial diagnosis were summarized, and Kaplan-Meier was used to analyze the differences in overall survival (OS) of patients with different karyotypes.Results:Among 351 patients with Ph-positive CML, 32 (9.1%) cases had variant translocation. At initial diagnosis, 47 cases had additional chromosomal abnormalities including 29 cases in chronic phase accounting for 9.15% (29/317) of all patients in chronic phase, 3 cases in accelerated phase accounting for 25.00% (3/12) of all patients in accelerated phase, 15 cases in blast crisis accounting for 68.18% (15/22) of all patients in blast crisis; there was a statistically significant difference in the chromosomal abnormalities rate of all different phases ( χ2=50.799, P<0.05). Among 47 Ph-positive CML patients with additional chromosomal abnormalities, 13 patients had complex karyotypes with more than 3 additional chromosomal abnormalities, the proportion of complex karyotypes in chronic phase, accelerated phase and blast crisis was 13.79% (4/29), 33.33% (1/3) and 53.33% (8/15), respectively, and the difference was statistically significant ( χ2=9.26, P<0.05). The study showed that the most common additional chromosomal abnormalities in chronic phase were double Ph (48.28%, 14/29) and -Y (10.34%, 3/29), while the most common chromosomal abnormalities in the blast crisis were +8 (26.67%, 4/15) and double Ph (26.67%, 4/15). Kaplan-Meier survival analysis showed that at initial diagnosis the OS time of patients with additional chromosomal abnormalities was worse than that of those with the non-additional chromosomal abnormalities group ( χ2 = 61.138, P<0.05). The OS of patients with complex karyotypes for Ph - positive CML patients with additional chromosomal abnormalities at initial diagnosis was worse than that of patients with non-complex karyotypes, and the difference was significant ( χ2 = 4.945, P < 0.05). Conclusions:The additional chromosomal abnormalities is closely related to the progression of CML, and the prognosis of CML patients with additional chromosomal abnormalities is poorer than that of patients with only Ph translocation. Moreover, the more complex the additional chromosomes are, the more likely blastic changes are, and the poorer prognosis. And additional chromosomeal abnormalities during the treatment of CML patients may also lead to the progression of blastic changes.

OBJECTIVETo compare the efficacy and toxicity of the chemotherapeutic regimen containing pirarubicin and mitoxantrone on the treatment of relapsed or refractory acute myeloid leukemia (AML) in adults.

METHODSIn this open prospective multicentre study, we randomly assigned patients with relapsed or refractory AML to receive TAE regimen (pirarubicin+cytarabine+etoposide) versus MAE regimen (mitoxantrone + cytarabine + etoposide). The efficacy and toxicity were compared between the two groups.

RESULTS56 patients entered this clinical trial. The complete remission (CR) rate on TAE arm was 79.0% versus 55.6% on MAE arm with the overall response (OR) rates of 86.8% versus 88.9%, respectively. The CR was higher on TAE arm (P=0.035) but with no significant difference between the two groups regarding the overall response (OR) rate. The regimens were well tolerated in both groups. Hematologic and non-hematologic toxicity were similar except relatively lower the mean dosage of G-CSF, red blood cells and platelets transfusion on TAE arm. No significant differences were seen between the two groups regarding the overall survival and relapse free survival rates.

CONCLUSIONTAE regimen might be an effective salvage therapy in patients with relapsed or refractory AML.

Adult ; Antineoplastic Combined Chemotherapy Protocols ; administration & dosage ; therapeutic use ; Dactinomycin ; administration & dosage ; Doxorubicin ; administration & dosage ; analogs & derivatives ; Etoposide ; administration & dosage ; Granulocyte Colony-Stimulating Factor ; administration & dosage ; Humans ; Leukemia, Myeloid, Acute ; drug therapy ; Methotrexate ; administration & dosage ; Prospective Studies ; Recurrence ; Remission Induction

ObjectiveTo evaluate the methodological quality of traditional Chinese medicine （TCM） diagnosis and treatment guidelines/consensus of constipation with Appraisal of Guidelines for Research and Evaluation Ⅱ （AGREE Ⅱ）tool， and to study the attention situation of the included Chinese patent medicines in China's National Reimbursement Drug List in the guidelines/consensus. MethodThe data of CNKI，VIP，Wanfang Data，SinoMed，PubMed and Cochrane from the inception of the databases to October 2021 were searched to collect the TCM diagnosis and treatment guidelines/consensus of constipation. Then，the diagnosis and treatment standards and recommended Chinese patent medicines were extracted. Two researchers assessed the methodological quality of the guidelines/consensus with AGREE Ⅱ tool independently. The quality of reports was evaluated by Reporting Items for practice Guidelines in HealThcare （RIGHT） Statement. The recommended Chinese patent medicines in the guidelines/consensus were compared with those in the National Reimbursement Drug List. ResultEleven consensus and 2 guidelines were included，involving 794 experts. The scores of AGREE II were clarity of presentation（59.0%），scope and purpose（44.0%），stakeholder involvement（23.1%），rigor of development （12.1%），applicability （11.1%），and editorial independence （8.3%） from high to low. Five articles were recommended at B level（recommended after revision） and 8 articles were at C level （not recommended）. The average scores of RIGHT Statement were as follows：basic information （93.59%），background （57.69%），evidence （18.46%），recommendations （20.88%），review and quality assurance （19.23%），funding，declaration and management of interests （0.00%）， and other information （0.00%）. The included guidelines/consensus recommended a total of 27 Chinese patent medicines，among which 20 were included in the National Reimbursement Drug List，with 4 species of Class A and 16 species of Class B， accounting for 74.1% of all recommended Chinese patent medicines. Ten purgative Chinese patent medicines in the National Reimbursement Drug List were recommended by the guidelines/consensus，accounting for 50% of all purgative drugs， and 8 were not recommended. There were prescriptions for purgation， for promoting digestion and removing food stagnation， for clearing heat and purging fire，and for warming the middle and dissipating cold，Tibetan medicine and Mongolian medicine. ConclusionBy the AGREE Ⅱ assessment，the methodological quality of the TCM diagnosis and treatment guidelines/consensus of constipation included in this study needed to be improved in the future. The report quality evaluated with RIGHT Statement was low. Most drugs included in the National Reimbursement Drug List were paid attention in the TCM diagnosis and treatment guidelines/consensus of constipation. Moreover，the drugs included in the National Reimbursement Drug List could basically fulfill the clinical needs reflexed from the guidelines/consensus recommendations. However， the reasons of some drugs failing to be included in the National Reimbursement Drug List needed to be studied in the future.

Based on the current laws and regulations framework of China， combined with practical cases， this paper systematically and comprehensively analyzes the supervision attributes， clinical trial supervision model and existing problems of tumor neoantigen vaccine， aiming to provide reference for the construction of the supervision system of clinical trial of tumor neoantigen vaccine in China. The results showed that， at present， the clinical trials of tumor neoantigen vaccine in China adopt a dual-track supervision model： clinical trials initiated by pharmaceutical enterprises and clinical trials initiated by researchers. This supervision model lags behind the development speed of the industry， mainly in the following aspects： challenges brought by dual- track supervision； the clinical trial data initiated by researchers are not effectively connected with new drug research applications； the guiding principles of clinical trial supervision need to be improved. Relevant medical institutions， regulatory authorities and cooperative enterprises can help the development of the regulatory system for clinical trials of tumor neoantigen vaccine in China from the above aspects.

Objective: To investigate the efficacy and safety of IA regimen which contains idarubicin (IDA) 8 mg/m², 10 mg/m² or 12 mg/m² as induction chemotherapy for adult patients with de-novo acute myeloid leukemia (AML) . Methods: A total of 1 215 newly diagnosed adult AML patients, ranging from May 2011 to March 2015 in the First Affiliated Hospital of Soochow University and other 36 clinical blood centers in China were enrolled in the multicenter, single-blind, non-randomized, clinical controlled study. To compare the response rate of complete remission (CR) , adverse events between different dose idarubicin combined with cytarabine (100 mg/m²) as induction chemotherapy in newly diagnosed patients of adult AML. Results: Of 1 207 evaluable AML patients were assigned to this analysis of CR rate. The CR rates of IDA 8 mg/m² group, IDA 10 mg/m² group and IDA 12 mg/m² group were 73.6% (215/292) , 84.1% (662/787) and 86.7% (111/128) , respectively (P<0.001) . After adjusted for age, blast ratio of bone marrow, FAB classification and risk stratification, the odds ratios (95% CI) of IDA 10 mg/m² group and IDA 12 mg/m² group were 0.49 (0.34-0.70) and 0.36 (0.18-0.71) , as compared with the IDA 8 mg/m² group (P<0.001, P=0.003) . In the intermediate and favorable groups, CR rates was 76.5% (163/213) , 86.9% (506/582) and 86.1% (68/79) in different doses of IDA (P=0.007) . Interestingly, IA regimen with IDA 10 mg/m² was the only beneficial factor affecting CR in this group after adjusted for age, blast ratio of bone marrow and FAB classification[OR=0.47 (95% CI 0.31-0.71) , P<0.001]. CR rates in adverse group was 50.0% (18/36) , 60.6% (43/71) and 81.8% (18/22) respectively (P=0.089) . However, the odds ratios (95% CI) of IDA 12 mg/m² when compared with the IDA 8 mg/m² was 0.22 (0.06-0.80) , after adjusted for age, blast ratio of bone marrow and FAB classification. The median time (days) of neutrophil count less than 0.5×10⁹/L in IDA 8 mg/m² group, IDA 10 mg/m² group and IDA 12 mg/m² group were 14 (11-18) , 15 (11-20) and 18 (14-22) , respectively (P=0.012) and of platelet count lower than 20×10⁹/L were 14 (7-17) , 15 (11-20) and 17 (15-21) , respectively (P=0.001) . The incidences of lung infection in the three groups were 9.8%, 13.5% and 25.2%, respectively (P<0.001) . Conclusions For young adult patients (aged 18-60 years) with AML in China, intensifying induction therapy with idarubicin 10 mg/m² is clinically superior to IDA 8 mg/m² and IDA 12 mg/m² in favorable intermediate AML subgroup. However, idarubicin 12 mg/m² is more suitable to adverse AML subgroup.

Inflammatory bowel disease (IBD) is a chronic intestinal disease with painful clinical manifestations and high risks of cancerization. With no curative therapy for IBD at present, the development of effective therapeutics is highly advocated. Drug delivery systems have been extensively studied to transmit therapeutics to inflamed colon sites through the enhanced permeability and retention (EPR) effect caused by the inflammation. However, the drug still could not achieve effective concentration value that merely utilized on EPR effect and display better therapeutic efficacy in the inflamed region because of nontargeted drug release. Substantial researches have shown that some specific receptors and cell adhesion molecules highly expresses on the surface of colonic endothelial and/or immune cells when IBD occurs, ligand-modified drug delivery systems targeting such receptors and cell adhesion molecules can specifically deliver drug into inflamed sites and obtain great curative effects. This review introduces the overexpressed receptors and cell adhesion molecules in inflamed colon sites and retrospects the drug delivery systems functionalized by related ligands. Finally, challenges and future directions in this field are presented to advance the development of the receptor-mediated targeted drug delivery systems for the therapy of IBD.

OBJE CTIVE To provide reference for the adjustment and optimization of the policies related to traditional Chinese medicine（TCM）injection in China. METHODS The policies related to TCM injections issued at the national level were collected from Jan. 1，1990 to May 31，2021. Based on the perspective of policy tool ，the content analysis and quantitative analysis were used to classify ，code and analyze the policy terms according to “policy serial number-chapter number-specific terms ”. RESULTS & CONCLUSIONS Totally 30 policy documents related to TCM injection were included ， with a total of 389 codes. Environment-based policy tools were the most widely used （79.95％），followed by supply-oriented policy tools ，accounting for 15.42％. Demand-based policy tools accounted for the least proportion （4.63％）. Among environment-based policy tools ，the regulatory and control policy tools （38.05％） received more attention，and the policy publicity （2.06％） received fewer applications. Among supply-oriented policy tools ，there were more applications of science and technology support （10.80％）， and fewer applications of capital investment （0.26％）. Among demand- based policy tools ，organizational coordination was the most widely used （3.34％），followed by experience demonstration （1.29％），which had not yet involved the relevant policies of international exchange. In order to promote the development of TCM injection ，it is necessary to appropriately reduce the application of environment-based policy tools ，increase the application of policies such as policy publicity ，and improve the external environment for TCM injection ；optimize the internal combination of supply-oriented policy tools ，increase the use of capital investment tools ，and effectively play the role of policy boosting；emphasize the application of demand-based policy XJY21013） tools to form an effective policy pulling force for the healthy development of TCM injection.

OBJECTIVE To analyze the research status， hotspots， and trend of the clinical comprehensive evaluation of Chinese patent medicine in China. METHODS Based on CNKI， VIP and Wanfang database， clinical comprehensive evaluation of Chinese patent medicine was used as the subject of retrieval， and the retrieval time was from the inception to October 30th， 2022. CiteSpace 6.1.R3 and VOSviewer were used to conduct a visualization analysis of the relative literature of clinical comprehensive evaluation of Chinese patent medicine in terms of annual publication quantity， authors， institutions， keywords， etc. RESULTS & CONCLUSIONS A total of 1 460 pieces of literature related to the clinical comprehensive evaluation of Chinese patent medicine were included. The overall annual publication quantity showed a growth trend. There were 714 authors in the included literature. The institutions with a large publication quantity included the Chinese Academy of Traditional Chinese Medicine， Beijing University of Chinese Medicine， Tianjin University of Traditional Chinese Medicine， etc.， and there was little cooperation among the authors and institutions. High-frequency keywords included Chinese patent medicine， safety， adverse drug reactions， rational drug use， etc. Research hotspots focused on the safety and effectiveness evaluation of Chinese patent medicine. It may be a research trend in this field to strengthen the prescription review of Chinese patent medicine， and build a multi-dimensional and multi-criteriaclinical comprehensive evaluation system for the rational use of Chinese patent medicine.