Objective: To evaluate the effect of aminolevulinic acid-based photodynamic therapy (ALA-PDT) on the expression of vascular endothelial growth factor (VEGF) and proliferating cell nuclear antigen (PCNA) in condyloma acuminatum (CA) tissues. Methods: A total of 56 patients with CA were enrolled from Department of Dermatology, The First Affiliated Hospital of Zhengzhou University from October 2016 to September 2017, and skin lesions were obtained before and 1 week after the first ALA-PDT treatment. Immunohistochemical SP method was used to determine the expression of VEGF and PCNA in keratinocytes in the CA tissues. Chi-square test and rank sum test were carried out to analyze differences between pre- and post-treatment expression rate and intensity of VEGF and PCNA, and Spearman correlation analysis was conducted to analyze the correlations between the protein expression of VEGF and PCNA. Results: The expression rates of VEGF and PCNA in keratinocytes in the CA tissues were 71.43% (40/56) and 73.21% (41/56) respectively before ALA-PDT, and 44.64% (25/56) and 41.07% (23/46) respectively after ALA-PDT. There were significant differences between pre- and post-treatment expression rate and intensity of VEGF and PCNA (expression rate: χ² = 8.25, 11.81 respectively, both P < 0.05; expression intensity: H = 11.29, 12.22 respectively, both P < 0.05) . The expression of VEGF was positively correlated with the expression of PCNA in the CA tissues before and after the ALA-PDT treatment (r_s = 0.202, 0.273, respectively, both P < 0.05) . Conclusion The expression of VEGF and PCNA decreased in CA tissues after ALA-PDT treatment, which may be one of the mechanisms underlying the treatment of CA with ALA-PDT.

OBJECTIVETo observe the inhibitory effect of citrus extract nobiletin on K562 cells xenograft in nude mice and discuss its anticancer activity and mechanism.

METHODThe model of K562 cells xenograft was established in nude mice. Twenty-five nude mice were divided to five groups. After 24 hrs of inoculation with K562 tumor cells subcutaneously, 1% CMC-Na in the nude mice of model control group, nobiletin (12.5, 25, 50 mg x kg(-1)) in the nude mice of nobiletin groups and CTX (20 mg x kg(-1)) in positive control group were administered once every day. The nude mice were killed at 18th day-point of administration. The inhibitory rate of nobiletin on tumor was calculated according to the measured tumor weight. Immunohistochemistry assay was used to determine the effect of nobiletin on VEGF expression and MVD, and CAM assay was used to detect the effect of nobiletin on vessel regeneration.

RESULTNobiletin have notable inhibition on K562 cells xenograft in nude mice comparing with model control group (P < 0.01), the inhibitory rate of nobiletin groups were 36% -58%. The results of immunohistochemical technology showed that the expression of VEGF in nobiletin groups decreased significantly comparing with the model control group (P < 0.05, P < 0.01, P < 0.01). Nobiletin could remarkably decrease the angiogenesis within tumor tissues. The expression of CD34 in nobiletin low dose group and high dose group was lower than that in model control group (P < 0.05, P < 0.01). The result of CAM indicated that 4 microg and 2 microg nobiletin could inhibit the new blood vessels of CAM (P < 0.01).

CONCLUSIONNobiletin inhibited the tumor growth and angiogenesis by reducing the VEGF expression of K562 cells xenograft in nude mice.

Angiogenesis Inhibitors ; pharmacology ; Animals ; Antineoplastic Agents ; pharmacology ; Citrus ; chemistry ; Disease Models, Animal ; Flavones ; pharmacology ; Gene Expression Regulation, Neoplastic ; drug effects ; Humans ; K562 Cells ; Male ; Mice ; Mice, Inbred BALB C ; Mice, Nude ; Neoplasm Transplantation ; Neoplasms ; drug therapy ; genetics ; metabolism ; Transplantation, Heterologous ; Vascular Endothelial Growth Factors ; genetics ; metabolism

Objective To evaluate the safety and efficacy of haploidentical hematopoietic stem cell transplan-tation(haplo-HSCT)treatment in children with hematological diseases.Methods Fifty-nine cases of less than 14 years old children with hematonosis were analyzed retrospectively,who were enrolled in the Aerospace Central Hospital from July 2012 to June 2016.And the evaluation was carried out by analyzing the success rate of implantation,occu-rrence rate of graft versus host disease(GVHD),infection rate and transplant related mortality(TRM),cumulative re-currence rate,overall survival rate(OS)and disease-free survival rate(DFS).Results In total of 59 cases,the 59 engraftments were successfully transplanted,the median time of leukocyte engraftment was 18(8-23)days,the median time of platelet engraftment was 21(11-68)days,the bone marrow was assessed 28 days after transplanta-tion,which showed that 59 patients achieved complete remission(CR)and DNA test confirmed complete donor chime-rism.With a median of follow-up time of 19(5-56)months,the cumulative recurrence rates ofⅠ,Ⅱgrade andⅢ,Ⅳ grade acute GVHD were(38.3 ± 6.3)%(23 cases)and(16.7 ± 4.8)%(10 cases),respectively,the chronic GVHD cumulative recurrence rate was(65.6 ± 7.5)%(30 cases),the cytomegalovirus(CMV)viremia cumulative recurrence rate was(45.1 ± 6.5)%(27 cases),the Epstein-Barr virus(EBV)viremia cumulative recurrence rate was(10.0 ± 3.9)%(6 cases),the viral cystitis cumulative recurrence rate was(20.0 ± 5.5)%(12 cases),the transplant related mortality was(12.8 ± 6.0)%,the 2-year cumulative recurrence rate of CR group was(8.0 ± 5.4)%,and that of non-remission(NR)group was(64.1 ± 11.9)%.The 2-year OS of CR group was(78.9 ± 7.5)%,the 2-year OS of NR group was(32.5 ± 12.9)%,the 2-year DFS of CR group was(79.5 ± 9.8)%,the 2 years DFS of NR group was(27.4 ± 7.9)%.Conclusions Haplo-HSCT is safe and effective in treating children with hematonosis,and haplo-HSCT has high survival rate and low recurrent,especially when transplantation is per-formed in the remission stage.But the prognosis of haplo-HSCT is poor in the refractory and relapsed patients,and to explore the preventing recurrence measures are very urgent.

Objective To analyze the clinical features and imaging findings of lesser trochanter osteoidosteoma,and to discuss the causes of its misdiagnosis as chronic osteomyelitis.Methods The clinical features,X-ray,CT and MRI findings of 6 cases with pathologically confirmed osteoidosteoma in the lesser trochanter were reviewed retrospectively.Symptoms included knee pain (1 case),thigh pain (4 cases)and hip joint pain(1 case);claudication(2 cases),and night pain(1 case).Five patients had right-side,and 1 patient had left-side involvement.All the 6 cases were misdiagnosed as chronic osteomyelitis before operation.Results Four patients had CT scan,which showed intra-cortical niduses at the lesser trochanters with peri-focal sclerosis,joint capsule swelling and joint effusion. Five patients had MRI exams,MR images showed bone marrow edema,synovial thickening,joint capsule swelling and joint effusion in all the 5 cases,but only 2 showed niduses.Six patients had X-ray imaging exams,X-ray images showed bone sclerosis without radiolucent nidus.Conclusion Osteoidosteoma in the lesser trochanter may display atypical clinical features that might be difficult to be differentiated from chronic osteomyelitis without sufficient examination.CT is best in showing niduses,except some niduses with atypical shape,superficial location and high-density calcification.MRI-T2WI is sensitive in showing the inflammation and bone marrow edema with high signal intensity,which may affect nidus displaying.X-ray images can only display bone sclerosis without niduses.

OBJECTIVE: To explore whether MRI fusion technology (combined T2-weighted imaging [T2WI] and fat-suppressed T2WI [T2WI-(FS)]) improves signal differences between anal fistulas and surrounding structures. MATERIALS AND METHODS: A total of 32 patients with confirmed diagnoses of anal fistula were retrospectively studied. All available T2WI and T2WI-(FS) images for each patient were used to generate fusion image (T2WI-(Fusion)) based on the addition of gray values obtained from each pixel via an MR post-processing work station. The discriminability of fistula, perianal sphincter, and perianal fat in T2WI, T2WI-(FS), and T2WI-(Fusion) images was quantified with Fisher's scoring algorithm. For subjective visual image assessment by researchers, five-point scale scores were determined using a modified double-stimulus continuous quality-scale test to evaluate T2WI-(FS), T2WI, enhanced axial three-dimensional-volumetric interpolated breath-hold examination (3D-VIBE), and T2WI-(Fusion) sequence images. The differences were subsequently compared. RESULTS: Mean Fisher scores for fistulas vs. sphincters obtained from T2WI-(Fusion) (F(Fusion-fistula) = 6.56) were significantly higher than those from T2WI (F(T2WI-fistula) = 3.35) (p = 0.001). Mean Fisher scores for sphincters vs. fat from T2WI-(Fusion) (F(Fusion-sphincter) = 10.84) were significantly higher than those from T2WI-(FS) (FS(FS-sphincter) = 2.57) (p = 0.001). In human assessment, T2WI-(Fusion) showed the same fistula discriminability as T2WI-(FS), and better sphincter discriminability than T2WI. Overall, T2WI-(Fusion) showed better discriminability than T2WI, T2WI-(FS), and enhanced 3D-VIBE images. CONCLUSION: T2WI and T2WI-(FS) fusion technology improves signal differences between anal fistulas and surrounding structures, and may facilitate better evaluation of anal fistulas and sphincters.
Anal Canal ; Diagnosis ; Fistula ; Humans ; Magnetic Resonance Imaging ; Rectal Fistula ; Retrospective Studies

Glycosphingolipids (GSLs) are widely distributed in the phospholipid bilayer of various cell membranes, which play an important role in maintaining cell membrane stability, and regulate various cellular processes including adhesion, proliferation, apoptosis and recognition, as well as participate in various cellular activities. In addition, GSLs are not only involved in the process of apoptosis, but also regulate multiple signals in tumorigenesis and tumor development. The tumor-associated GSLs are expected to be used as diagnostic markers and immunotherapeutic targets for malignant tumors. These findings have important implications for the study of apoptosis and provide the new direction of tumor therapy. This review summarized the latest research progress of GSLs-mediated apoptosis and its effect on the genesis, development and metastasis of tumor cells. Moreover, we discussed the metabolic pathway of GSLs-mediated apoptosis and its application in tumor therapy, as well as the development prospect of targeted therapy strategies based on GSLs.
Humans ; Glycosphingolipids/metabolism* ; Apoptosis ; Cell Membrane ; Neoplasms/metabolism*

Objective To study the rural residents′ satisfaction for services of village clinics in Shandong province, identify the influencing factors and put forward feasible suggestions and countermeasures. Methods The method of multi-stage stratified random sampling was used in 54 villages of 18 counties from six prefectures,with 1 590 rural residents randomly sampled for questionnaire survey and interview. This survey called into play the composition ratio for descriptive analysis,and univariate analysis and multinomial logistic regression for identifying the influencing factors. Results The rural residents′overall satisfaction for services of village clinics was acceptable as 65.6% of them were satisfied,yet still at a low level. Major influencing factors for the satisfaction are service attitude and communication ability of rural doctors, drug availability at village clinics, and conditions of equipments and environment. Conclusions Authors proposed such measures as strengthening training of the service attitude and communication ability of rural doctors, scientifically adjusting and refining the types and quantities of essential drugs and continuing to better the conditions of equipments and environment of village clinics. These measures aim at further improving rural residents′satisfaction for services of village clinics.

As a generally-recognized-as-safe microorganism, Saccharomyces cerevisiae is a widely studied chassis cell for the production of high-value or bulk chemicals in the field of synthetic biology. In recent years, a large number of synthesis pathways of chemicals have been established and optimized in S. cerevisiae by various metabolic engineering strategies, and the production of some chemicals have shown the potential of commercialization. As a eukaryote, S. cerevisiae has a complete inner membrane system and complex organelle compartments, and these compartments generally have higher concentrations of the precursor substrates (such as acetyl-CoA in mitochondria), or have sufficient enzymes, cofactors and energy which are required for the synthesis of some chemicals. These features may provide a more suitable physical and chemical environment for the biosynthesis of the targeted chemicals. However, the structural features of different organelles hinder the synthesis of specific chemicals. In order to ameliorate the efficiency of product biosynthesis, researchers have carried out a number of targeted modifications to the organelles grounded on an in-depth analysis of the characteristics of different organelles and the suitability of the production of target chemicals biosynthesis pathway to the organelles. In this review, the reconstruction and optimization of the biosynthesis pathways for production of chemicals by organelle mitochondria, peroxisome, golgi apparatus, endoplasmic reticulum, lipid droplets and vacuole compartmentalization in S. cerevisiae are reviewed in-depth. Current difficulties, challenges and future perspectives are highlighted.
Saccharomyces cerevisiae/metabolism* ; Saccharomyces cerevisiae Proteins/metabolism* ; Golgi Apparatus/metabolism* ; Metabolic Engineering ; Vacuoles/metabolism*

ObjectiveTo explore the current status and issues regarding the application of ancient books in clinical practice guidelines and expert consensus of traditional Chinese medicine （TCM） published in China， and to provide methodological recommendations for the incorporation of ancient books in the development of TCM guidelines. MethodsWe searched China National Knowledge Infrastructure （CNKI）， WanFang Data， VIP， SinoMed， PubMed， Embase， as well as six industry websites including China Association of Chinese Medicine， National Group Standards Information Platform， and Chinese Association of the Integration of Traditional and Western Medicine，etc. TCM clinical practice guidelines or expert consensus issued during January 1st， 2017， to November 26th， 2022 were searched. Clinical practice guidelines or expert consensus that explicitly referred to ancient books were included， and the content regarding the searching for ancient books， sources of access to ancient books， methods of evaluating the level of evidence， methods of evaluating the level of recommendation， and methods of evaluating the evidence for the ancient books were analysed. ResultsA total of 1,215 TCM clinical practice guidelines or expert consensus were retrieved， with 442 articles explicitly mentioning the application of ancient books， including 300 （67.87%） clinical practice guidelines and 142 （32.13%） expert consensus. Sixty of the 442 publications explicitly reported that ancient books searching had been conducted （13.57%）； among these 60 publications 27 （45.00%） explicitly reported ancient books searching strategies， and the most frequent method was manual searching with a total of 24 articles （40.00%）. The most popular search source was Chinese Medical Dictionary， a TCM classics database， with a total of 18 articles. 197 articles （44.57%） explicitly reported the evaluation criteria for the level of evidence， of which 141 articles （71.57%） involved the evaluation criteria for the ancient books； 413 articles （93.44%） mentioned ancient books in the recommendations， and only the source of formula name was mentioned in 409 （99.03%） of the publications. ConclusionThe current application of ancient books in TCM clinical practice guidelines and expert consensus is limited， with issues of non-standard searching and evaluation methods. Standar-dization and uniformity are needed in evidence grading and recommendation standards. Future research should clarify the scope and methods of applying ancient book， emphasize their integration with modern research evidence， and enhance their value and quality in the development of TCM clinical practice guidelines.