Background and purpose:In 2016 the National Cancer Institute(NCI)decided stopping to use NCI-60 cell lines for drug screening,suggesting that tumor cell lines were losing their value as a tool for drug discovery and basic research.The reason for NCI-60 cells'retirement'was that the preclinical studies based on traditional cellular and animal models did not obtain the corresponding expected efficacy in clinical trials.Since the major cancer behaviors,such as proliferation and metastasis,are fundamentally altered with long-term culture,the tumor cell lines are not representative of the characteristics of cancer in patients.Currently,scientists hope to create a new cancer model that are derived from fresh patient samples and tagged with details about their clinical past.Our purpose was to create patient-derived breast cancer primary cell lines as new cancer model for drug screening and basic research.Methods:Breast cancer tissues were collected in the Department of Breast Surgery,Affiliated Hospital of Guizhou Medical University.The collection of tumor tissue samples was approved by the Ethics Committee of the Affiliated Hospital of Guizhou Medical University(approval number:2022 ethics No.313),and the collection and use of tumor tissues complied with the Declaration of Helsinki.The primary breast cancer cell lines were isolated from the patient's breast cancer tissues and cultured in BCMI medium.After the cells proliferated,the media were replaced with DEME medium.Cell line STR genotyping was done to determine cell-specific genetic markers and identification.Clone formation assay and transplantation assay were done to analyze the ability of breast cancer primary cell lines to form tumors.Results:We created 6 primary breast cancer cell lines.The 6 primary breast cancer cell lines from the patients were tagged with the definitively clinicopathological features,clinical diagnosis,therapeutic regimens,clinical effectiveness and prognostic outcomes.The STR genotyping assays identified the genetic markers and determined the identities of the 6 primary breast cancer cell lines.Clone formation assays and transplantation assay showed that the proliferative capacities of the patient-derived primary breast cancer cell lines were significantly greater compared with the conventional breast cancer cell lines.Conclusion:We created a panel of 6 patient-derived primary breast cancer cell lines as new cancer model for drug screening and basic research in breast cancer.

Purpose This study uses the diffusion tensor imaging to explore diffusion metrics changes of corpus callosum subregion,and to further analyze the relationship among these changes and the cognitive and emotional in adults with primary hypothyroidism.Materials and Methods From October 2019 to September 2021,32 hypothyroidism patients were recruited from Gansu Provincial Hospital,whereas 33 healthy controls were recruited through advertisements.The comprehensive thyroid-related hormone levels tests,as well as neurocognitive/neuropsychiatric assessment and diffusion tensor imaging data of all participants were carried out.The differences in corpus callosum subgroups of diffusion metrics between the two groups were recorded and compared,the partial relationships between these diffusion metrics and thyroid-related hormone levels and neurocognitive/neuropsychiatric function were analyzed and measured.Receiver operating characteristic curves were constructed to evaluate the diagnostic performance.Results Lower fraction anisotropy,higher mean diffusivity and radial diffusivity in genu and body of the corpus callosum and higher axial diffusivity in genu of the corpus callosum were found in hypothyroidism compared with healthy controls(P<0.01).These diffusion metrics were negatively correlated with cognition and emotion(r=-0.448-0.440,P=0.010-0.043),and the fraction anisotropy value in genu of the corpus callosum had the largest area under the curve(0.777).Conclusion Hypothyroidism patients show widespread microstructural changes within the genu and body of the corpus callosum,which,respectively,associated with cognition and emotion.This study provides a new perspective to further understanding the pathophysiology of the cerebral impairment in hypothyroidism.

Objective: To study the effect of a space stabilizing device on the capacity for osteogenesis in the bone-grafted area. Methods: Patients with anterior teeth defects as well as labial alveolar ridge defects were randomly divided into two groups: the experimental group was treated using a space stabilization device after guided bone regeneration whereas the control group received regular guided bone regeneration. The CBCT data was analyzed prior to, immediately and 6 months after procedure to compare the osteogenesis with or without the device. Results: Seventeen bone-grafted sites were examined(7 in the experimental group and 10 in the control group). At 2 mm and 4 mm below the alveolar ridge, the horizontal bone resorption rate in the experimental group was significantly lower than the corresponding level in the control group(P=0.001). The horizontal bone resorption rate at 2 mm below the alveolar ridge of each group was significantly higher than that at 4 mm below the alveolar ridge in corresponding groups(P=0.003). Conclusion The space stabilizing device used in this study has a positive clinical impact on preserving space stability and minimizing bone resorption.

Objective:To analyse China′s Traditional Chinese Medicine(TCM) health service policy from the perspective of policy life cycle, so as to provide reference for improving the policy system of TCM health service.Methods:The official websites of national government agencies were searched for policy documents on TCM health service from 2012 to 2022, using the keywords of " Chinese medicine" " Traditional Chinese Medicine" and " health service", and policy text entries were extracted and coded. A two-dimensional analytical framework of policy tools(supply, demand, and environment) and policy life cycle(agenda setting, policy formulation, policy implementation, and policy evaluation) was constructed to quantitatively analyze the policy texts.Results:A total of 58 policy documents were included, containing 2 898 text entries. The distribution of policy instruments was uneven, with a high percentage of entries using supply-based instruments(40.57%, 1 176 entries), followed by environmental instruments(38.86%, 1 126 entries) and demand-based instruments(20.57%, 596 entries). From the perspective of policy cycle, the policy tools were mainly concentrated in the stages of policy formulation(53.77%, 1 558 entries) and policy implementation(36.86%, 1 068 entries), while the policy tools in the stages of agenda setting(4.97%, 144 entries) and policy evaluation(4.40%, 128 entries) needed to be strengthened.Conclusions:In recent years, the distribution of policy tools in China′s TCM health service policy was uneven, and the articulation of the stages in the policy life cycle needed to be strengthened.

Objective: To investigate the trends in mortality and life lost due to cancer among residents in Ouhai District, Wenzhou City from 2013 to 2020, so as to provide the evidence for formulating the cancer control strategy. Methods: The mortality data of cancer patients in Ouhai District from 2013 to 2020 were collected through Zhejiang Provincial Information Management System for Surveillance of Chronic Diseases. The crude mortality, standardized mortality, years of potential life lost ( YPLL ), years of potential life lost rate ( YPLLR ), standardized years of potential life lost ( SYPLL ), standardized years of potential life lost rate ( SYPLLR ), average years of life lost ( AYLL ) and annual percent change ( APC ) were estimated to analyze the trends in mortality and life lost due to cancer. Results: Totally 5 435 deaths occurred due to cancer in Ouhai District from 2013 to 2020, and the crude and standardized mortality rates were 154.10/105 and 119.41/105, respectively. The crude mortality of cancer was higher in men than in women ( 196.26/105 and 111.09/105; χ2=415.623, P<0.001 ). The standardized mortality of cancer among whole populations, the crude mortality in men and the standardized mortality in men showed a tendency towards a reduction ( P<0.05 ), with APC of -3.25%, -2.18% and -4.78%, respectively. The crude mortality of cancer showed an upward trend with age ( χ2trend=9 260.583, P<0.001 ). Lung cancer, liver cancer, stomach cancer, colorectal cancer and esophagus cancer were the five leading causes of cancer-related mortality, which accounted for 66.68% of all cancer mortality. Liver cancer, lung cancer, stomach cancer, colorectal cancer and brain cancer were the five leading causes of life lost, with YPLL of 11 191.50, 8 231.00, 6 000.00, 3 892.00 and 2 693.50 person-years, respectively. Leukemia was the primary cause of AYLL ( 25.17 years per person ). Conclusions Both the standardized mortality and the life lost due to cancer showed a tendency towards a reduction in Ouhai District from 2013 to 2020, and men and the elderly were high-risk populations. Lung cancer, liver cancer, stomach cancer, colorectal cancer, leukemia, brain cancer, and female breast cancer should be listed among cancers in Ouhai District prioritized for control

Objective:To investigate the immune effects of Clostridium difficile toxoid B (CdtB) vaccine formulated with different mucosal adjuvants through microneedle immunization, and to provide ideas for the prevention and treatment of Clostridium difficile infection. Methods:CdtB vaccine was prepared with purified Clostridium difficile toxin B(TcdB) after formaldehyde detoxification. Female BALB/c mice were immunized with different doses of vaccine alone or in combination with mucosal adjuvants. The titers of specific serum IgG and fecal IgA were detected at 0 d, 7 d, 14 d, 28 d and 42 d after immunization. The protective effects of CdtB vaccine were evaluated by cell neutralization assay and Clostridium difficile challenge infection. Results:(1) With the increase of immune dose, the mice immunized with CdtB vaccine alone by microneedle not only produced better serum specific IgG, but also had higher level of IgA in feces. (2) When the mice were immunized with CdtB vaccine containing LT or CTB adjuvant by microneedle, the trend of serum specific IgG titer in each group increased with the increase of immune dose, especially in the group containing LT adjuvant. There were significant differences in the trend of specific IgA titer in feces between the adjuvant groups and the group without adjuvant, but the adjuvant effect was not obvious. (3) No significant difference in serum IgG titer was observed between the mice immunized with 10 μg CdtB by microneedle or intraperitoneal injection, but microneedle immunization significantly increased fecal IgA level. (4) The neutralization titers of specific antibodies in mouse serum after immunization and the test results of challenge protection in mice confirmed that the use of CdtB vaccine had certain protective effects.Conclusions:CdtB vaccine had better immune effects in mice through microneedle immunization, but the adjuvant effects of LT and CTB were not significant.

Anaplastic lymphoma kinase (ALK) fusion gene, as a tumor driver gene, was crucial for the occurrence and development of non-small cell lung cancer (NSCLC). Recently, targeted ALK fusion gene has become the main treatment method for ALK-positive NSCLC. The first and second generation ALK inhibitors (ALKi), such as crizotinib, ceritinib, alectinib and ensartinib have been approved in China. However, there was no guidance for the management of ALKi adverse reactions. Therefore, this "Recommendations from experts in the management of adverse reactions to ALK inhibitors (2021 version)" has been summarized, led by Lung Cancer Professional Committee of Sichuan Cancer Society and Sichuan Medical Quality Control Center for Tumor Diseases, to provide practical and feasible strategies for clinical ALKi management specification of adverse reactions.
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Carcinoma, Non-Small-Cell Lung ; Crizotinib ; Humans ; Lung Neoplasms/genetics* ; Protein Kinase Inhibitors/adverse effects* ; Receptor Protein-Tyrosine Kinases/antagonists & inhibitors*

【Objective】 To develop a new approach for the preparation of 0.7~0.8 hematocrit concentrated washed red blood cells(RBCs) for fetal anemia in utero transfusion and apply it in clinical. 【Methods】 The erythrocyte suspension and frozen stored erythrocytes within expiry date in Guangzhou Blood Center from March 2020 to February 2021 were taken to prepare concentrated washed RBCs. According to the derivation formula, corresponding weight of RBC preservation solution was added to obtain 0.7~0.8 hematocrit concentrated washed RBCs. Routine blood test data were statistically analyzed by single-sample t test, and P<0.05 was considered statistically significant. Qualified Rh-negative/ O-type 0.7~0.8 hematocrit concentrated RBCs within expiry date were used in clinical intrauterine blood transfusion. 【Results】 The hematocrit of concentrated washing RBCs prepared by the new approach could reach 0.7~0.8. The RBCs count (8.389 ±0.808)×1 0¹²/ L and hemoglobin content(233.730±15.498)g/L were higher while the erythrocyte count (0.732±0.469)×10⁹ /L and platelets count(26.000±26.276)×10⁹/L were lower than the normal values of adults. The mean erythrocyte volume(fL), hemoglobin content(pg) and concentration(g/L )were 88.123±6.359, 30.004±2.809 and 339.980±11.865, respectively, which were normal values of adults. Fetal anemia was significantly improved and the prognosis was good after intrauterine blood transfusion. 【Conclusion】 The 0.7~0.8 hematocrit concentrated washed RBCs prepared by the new approach is consistent with the special blood requirements during fetal anaemia transfusion, meets the clinical treatment standards, and can be applied in clinical.

Objective:To explore the application effect and evaluation of virtual reality technology in oral implant therapy training.Methods:In November 2018, one adult patient (female, 36 years old) with missing right mandibular first molar was treated in the Department of Implantology, School and Hospital of Stomatology, Fujian Medical University. The three-dimensional virtual models of mandible and implant surgery tools were established, and the virtual reality software (Unity 3D 5.5.1) was imported. Combined with the virtual reality head mounted display, a virtual reality training system simulating the dental implant treatment process was independently developed. Ten refresher doctors and 20 graduate students in Department of Implantology, School and Hospital of Stomatology, Fujian Medical University from September 2018 to December 2019 were recruited as the experimental objects (no clinical experience was found). According to the level and seniority of doctors, they were randomly divided into virtual training group and conventional training control group, which made the two groups comparable, with 15 in each group. Subjective scores (including anatomical structure, surgical field of vision, cavity preparation, implant placement and process mastery) were given after the corresponding training in the two groups, and the virtual reality training system was used to test. The mesial and distal direction, buccolingual direction, depth and angle deviation of implants before and after the training were analyzed, and the differences between the two groups were compared.Results:The subjective scores of five dimensions in the virtual training group were significantly higher than those in the conventional training control group ( P<0.05). In the virtual training group, the mesial and distal, buccolingual, depth and angle deviation of implants were (0.73±0.33), (0.78±0.41), (0.61±0.32) mm and 6.66°±3.87°. All of them were significantly lower than those in the control group [(0.85±0.32), (1.12±0.38), (0.89±0.24) mm and 9.68°±3.74°] ( P<0.05). Conclusions:The self-developed virtual reality system of oral implant has good application effect, good operability and predictability. It can be effectively carried out in implant education and training, and it can strengthen skills of doctors, and is conducive to the practical operation.

BACKGROUND: Anaplastic lymphoma kinase (ALK) rearrangement is a common driver gene of non-small cell lung cancer (NSCLC). Ceritinib is a second-generation ALK inhibitor, which can bring survival benefits to ALK-positive metastatic NSCLC. However, few studies focus on the safety and efficacy of ceritinib in China. Therefore, this study intends to investigate the safety and preliminary efficacy of ceritinib 450 mg with meals in Chinese patients with ALK-positive NSCLC through a real world study. METHODS: From October 2018 to December 2019, patients with ALK-positive NSCLC from 8 medical centers in Sichuan province were recruited in this study. All of these participants received ceritinib 450 mg/d with food. The basic characteristics, adverse effects (AEs) and responses were collected and analyzed in order to evaluate the safety and efficacy of ceritinib. RESULTS: A total of 109 patients were included in this study. Data cutoff was January 23, 2020. The median duration of treatment exposure was 5.87 mon (range: 0.4 mon-15.7 mon). Total AEs were reported in 98 (89.9%) of 109 patients and grade 3 or 4 AEs were reported in 22.9% of patients. Most common AEs (mainly grade 1 or 2) were diarrhea (60.6%), elevated alanine aminotransferase (ALT)(38.5%) and aspartate aminotransferase (AST)(37.6%). As of data cutoff, 45 patients discontinued ceritinib. The overall response rate (ORR) was 37.6% (95%CI: 28.5%-47.4%) and disease control rate (DCR) was 86.2% (95%CI: 78.3%-92.1%). CONCLUSIONS The treatment of ceritinib 450 mg with food for Chinese ALK-positive NSCLC patients had a good safety profile and favorable DCR in real-world setting. However, this conclusion needs to be further verified by large sample, prospective trials.