Objective:To discuss the inhibitory effect of schisandrin B(SchB)on the migration and invasion of the pancreatic cancer Pan02 cells,and to clarify its mechanism.Methods:The pancreatic cancer Pan02 cells were treated with different concentrations of SchB(0,0.78,1.56,3.12,6.25,12.50,and 25.00 mg·L-1)for 24,48,and 72 h.CCK-8 method was used to detect the survival rates of the cells in various groups,and the concentration of SchB for the subsequent experiments was confirmed.The Pan02 cells were divided into control group,2.5 mg·L-1 SchB group,5.0 mg·L-1 SchB group,and 10.0 mg·L-1 SchB group.Wound healing assay was used to detect the wound healing rates of the Pan02 cells in various groups;Transwell chamber assay was used to detect the numbers of migration and invasion Pan02 cells in various groups;Western blotting method was used to detect the expression levels of Vimentin and N-cadherin proteins in the Pan02 cells in various groups.The mouse models of subcutameous transplanted tumor of pancreatic cancer cells were established.Ten successfully modeling mice were randomly divided into control group and SchB group(n=5).After 28 d of treatment,the weights of tumor of the mice were determined;immunohistochemistry method was used to detect the expressions of Vimentin and N-cadherin proteins in tumor tissue of the mice in various groups.Results:The CCK-8 results showed that compared with control group,the survival rates of the pancreatic cancer Pan02 cells in different concentrations of SchB groups were decreased(P＜0.05 or P＜0.01).The wound healing results showed that compared with control group,the wound healing rates of the cells in 2.5,5.0,and 10.0 mg·L-1 SchB groups were decreased(P＜0.05 or P＜0.01).The Transwell chamber results showed that compared with control group,the numbers of migration and invasion Pan02 cells in 2.5,5.0,and 10.0 mng·L-1SchB groups were decreased(P＜0.05 or P＜0.01).The Western blotting results showed that compared with control group,the expression levels of Vimentin and N-cadherin proteins in the Pan02 cells in 2.5,5.0,and 10.0 mg·L-1 SchB groups were decreased(P＜0.05 or P＜0.01).Compared with control group,the tumor volume and weight of the mice in SchB group were significantly decreased(P＜0.01).The immunohistochemistry results showed that compared with control group,the positive expression rates of Vimentin and N-cadherin proteins in tumor tissue of the mice in SchB group were significantly decreased(P＜0.01).Conclusion:SchB can inhibit the proliferation,migration,and invasion of the pancreatic cancer Pan02 cells,and its mechanism is related to the reduction of expressions of Vimentin and N-cadherin proteins.

Peri-implant keratinized mucosa (PIKM) augmentation refers to surgical procedures aimed at increasing the width of PIKM. Consensus reports emphasize the necessity of maintaining a minimum width of PIKM to ensure long-term peri-implant health. Currently, several surgical techniques have been validated for their effectiveness in increasing PIKM. However, the selection and application of PIKM augmentation methods may present challenges for dental practitioners due to heterogeneity in surgical techniques, variations in clinical scenarios, and anatomical differences. Therefore, clear guidelines and considerations for PIKM augmentation are needed. This expert consensus focuses on the commonly employed surgical techniques for PIKM augmentation and the factors influencing their selection at second-stage surgery. It aims to establish a standardized framework for assessing, planning, and executing PIKM augmentation procedures, with the goal of offering evidence-based guidance to enhance the predictability and success of PIKM augmentation.
Humans ; Consensus ; Dental Implants ; Mouth Mucosa/surgery* ; Keratins

Metachromatic leukodystrophy (MLD) is an inherited disease caused by a deficiency of the enzyme arylsulfatase A (ARSA). Lentivirus-modified autologous hematopoietic stem cell gene therapy (HSCGT) has recently been approved for clinical use in pre and early symptomatic children with MLD to increase ARSA activity. Unfortunately, this advanced therapy is not available for most patients with MLD who have progressed to more advanced symptomatic stages at diagnosis. Patients with late-onset juvenile MLD typically present with a slower neurological progression of symptoms and represent a significant burden to the economy and healthcare system, whereas those with early onset infantile MLD die within a few years of symptom onset. We conducted a pilot study to determine the safety and benefit of HSCGT in patients with postsymptomatic juvenile MLD and report preliminary results. The safety profile of HSCGT was favorable in this long-term follow-up over 9 years. The most common adverse events (AEs) within 2 months of HSCGT were related to busulfan conditioning, and all AEs resolved. No HSCGT-related AEs and no evidence of distorted hematopoietic differentiation during long-term follow-up for up to 9.6 years. Importantly, to date, patients have maintained remarkably improved ARSA activity with a stable disease state, including increased Functional Independence Measure (FIM) score and decreased magnetic resonance imaging (MRI) lesion score. This long-term follow-up pilot study suggests that HSCGT is safe and provides clinical benefit to patients with postsymptomatic juvenile MLD.
Humans ; Leukodystrophy, Metachromatic/genetics* ; Pilot Projects ; Genetic Therapy/methods* ; Hematopoietic Stem Cell Transplantation ; Male ; Follow-Up Studies ; Female ; Lentivirus/genetics* ; Child ; Child, Preschool ; Hematopoietic Stem Cells/metabolism* ; Cerebroside-Sulfatase/metabolism* ; Adolescent

A case of multiple intracranial venous sinus thrombosis caused by a calreticulin(CALR)gene mutation in essential thrombocythemia is reported including the diagnosis,treatment process and outcome.The patient was a 39-year-old female presenting with headache,slurred speech and limb weakness.Physical examination revealed unclear speech,dysarthria and decreased muscle strength in the left limb.On the basis of anticoagulation therapy,mechanical thrombectomy,intrasinus contact thrombolysis,decompressive craniectomy and cytoreductive therapy targeting the cause were performed.After treatment,the venous sinuses were completely recanalized and the prognosis was good.There are no relevant literature reports on intracranial venous sinus thrombosis caused by CALR gene mutation in essential thrombocythemia.The diagnosis and treatment strategy of this case provide a reference for the identification and treatment of similar cases in clinical practice.

A case of multiple intracranial venous sinus thrombosis caused by a calreticulin(CALR)gene mutation in essential thrombocythemia is reported including the diagnosis,treatment process and outcome.The patient was a 39-year-old female presenting with headache,slurred speech and limb weakness.Physical examination revealed unclear speech,dysarthria and decreased muscle strength in the left limb.On the basis of anticoagulation therapy,mechanical thrombectomy,intrasinus contact thrombolysis,decompressive craniectomy and cytoreductive therapy targeting the cause were performed.After treatment,the venous sinuses were completely recanalized and the prognosis was good.There are no relevant literature reports on intracranial venous sinus thrombosis caused by CALR gene mutation in essential thrombocythemia.The diagnosis and treatment strategy of this case provide a reference for the identification and treatment of similar cases in clinical practice.

Objective:To discuss the inhibitory effect of Schisandrin B on the proliferation of pancreatic cancer Pan02 cells,and to clarify the mechanism.Methods:CCK-8 method was used to detect the proliferation rates of the Pan02 cells after treated with different concentrations(0,0.78,1.56,3.12,6.25,12.50,and 25.00 mg·L-1)of Schisandrin B to select the optimal concentration and treatment time of Schisandrin B.The mouse pancreatic cancer Pan02 cells were divided into control group(0 mg·L-1 Schisandrin B),2.5 mg·L-1 Schisandrin B group,5.0 mg·L-1 Schisandrin B group,and 10.0 mg·L-1 Schisandrin B group.The morpholoy of Pan02 cells invarious groups was observed with light microscope;5-ethynyl-2'-deoxyuridine(EdU)staining assay was used to detect the positive expression rates of the Pan02 cells in various groups;flow cytometry was used to detect the percentages of the Pan02 cells at different cell cycles and the apoptotic rates of the cells in various groups;Western blotting method was used to detect the expression levels of cell cycle and apoptosis-related proteins in the cells in various groups.Results:The CCK-8 method results showed that after treated with Schisandrin B for 48 and 72 h,compared with 0 mg·L-1 Schisandrin B,the proliferation rates of the Pan02 cells after treated with different concentrations of Schisandrin B were decreased(P<0.01),especially at 72 h.0.25,5.0,and 10.0 mg·L-1 Schisandrin B were selected to treat the Pan02 cells,and 72 h was the treatment time.In control group,the Pan02 cells had a spindle shape,with good condition,and grew closely adhered to the wall with normal organelles and cytoplasm,in 2.5 and 5.0 mg·L-1 Schisandrin B groups,the cell volume was decreased,the intercellular adhesion was disappeared,and the cell membrane was intact but more permeable;the cytoplasm shrank and vacuolar structures appeared inside the cells,with some fragmented and floating on the surface of the solution;in 10.0 mg·L-1 Schisandrin B group,the Pan02 cells exhibited notable apoptotic bodies,indicating an apoptotic state.The EdU staining results showed that compared with control group,the rates of EdU positive cells in 2.5,5.0,and 10.0 mg·L-1 Schisandrin B groups were significantly decreased(P<0.01).The flow cytometry results showed that compared with control group,the percentages of the cells at S phase in 2.5,5.0,and 10.0 mg·L-1 Schisandrin B groups were significantly increased(P<0.01),while the percentages of the cells at G2/M phase were significantly decreased(P<0.01),and the percentages of the cells at G0/G1 phase in 5.0 amd 1.0 mg·L-1 Schisandrin groups were decreased(P<0.01);compared with control group,the apoptotic rates of the cells in 2.5,5.0,and 10.0 mg·L-1 Schisandrin B groups were significantly increased(P<0.01).The Western blotting results showed that compared with control group,the expression levels of p27,B-cell lymphoma 2(Bcl-2)associated X protein(Bax),cleaved cysteine aspartic acid protease-3(cleaved Caspase-3),and cleaved poly adenosine diphosphate(ADP)ribose polymerase(cleaved PARP)proteins in the cells in 2.5 mg·L-1 Schisandrin B group were significantly increased(P<0.05 or P<0.01),the expression levels of cyclin A2,cyclin E2,and Bcl-2 proteins in the cells in 5.0 and 10.0 mg·L-1 Schisandrin B groups were significantly decreased(P<0.05 or P<0.01),while the expression levels of p27,Bax,cleaved Caspase-3,and cleaved PARP proteins in the cells in 5.0 and 10.0 mg·L-1 Schisandrin B groups were significantly increased(P<0.01).Conclusion:Schisandrin B has an inhibitory effect on proliferation of the pancreatic cancer Pan02 cells,and its mechanism may be related to the activation of the cysteine aspartic acid protease-3(Caspase-3)pathway to induce the apoptosis and activating p27 protein to induce the arrest of cell cycle at S phase.

Objective:To investigate the efficacy and safety of SIMPLE regimen in the treatment of extranodal NK/T-cell lymphoma (ENKTCL).Methods:The clinical data of 11 patients with ENKTCL who were admitted to the University of Hong Kong-Shenzhen Hospital from January 2012 to January 2022 were retrospectively analyzed. The patients received 4-6 courses of SIMPLE (cisplatin, gemcitabine, ifosfamide, etoposide, dexamethasone, and pegasparaginase) regimen chemotherapy, and stage Ⅰ and Ⅱ patients who also received local radiotherapy after 2 or 3 courses of chemotherapy. Patients were evaluated for mid-treatment and end-of-treatment outcomes, and the adverse effects of patients were evaluated in each treatment cycle. The Kaplan-Meier method was used to analyze the progression-free survival (PFS) and overall survival (OS) of the 11 patients.Results:All 11 patients were nasal type, with the median age of 41 years old (26-67 years old), including 5 males and 6 females, 3 relapsed cases and 8 newly treated cases. Of the 10 patients evaluated for efficacy, 9 achieved complete remission and 1 achieved at least partial remission (efficacy was assessed based on follow-up). All 11 patients were followed up for a median time of 50 months (15-72 months) and 2 relapsed patients died due to disease progression. The expected 5-year PFS rate and OS rate of 11 patients were both 90.0%, and the expected 5-year OS rate was 100.0% and 66.6% in newly treated and relapsed patients, respectively. Common adverse effects were hematologic adverse reactions, infections, gastrointestinal symptoms, elevated transaminases, and hypofibrinogenemia, all of which were curable. There is no treatment-related death.Conclusions:The SIMPLE regimen for the treatment of ENKTCL has a high remission rate, the patients have long survival time, and the regimen is moderately well tolerated.

Cyclodextrin metal-organic framework (CD-MOF) as a highly porous supramolecular carrier could be one of the solutions to the insolubility of isosteviol (STV). The solubility of STV was lower than 20.00 ng/mL at pH 1.0 and pH 4.5, whilst its solubility increased to 20,074.30 ng/mL at pH 6.8 and 129.58 ng/mL in water with a significant pH-dependence. The

Objective: To explore the effects of dendritic epidermal T cells (DETC) on proliferation and apoptosis of epidermal cells in wound margin of mice and its effects on wound healing. Methods: Twenty-eight healthy specific pathogen free (SPF) C57BL/6 wild-type (WT) male mice aged 8-12 weeks and 60 SPF T lymphocyte receptor δ-knockout (TCR δ^-/-) male mice aged 8-12 weeks were selected to conduct the following experiments. (1) Eight WT mice were selected to isolate epidermal cells and primarily culture DETC according to the random number table. Morphological observation and purity identification of DETC by flow cytometer were detected immediately after culture and on culture day (CD) 15 and 30, respectively. (2) According to the random number table, 5 WT mice and 5 TCR δ^-/- mice were selected and enrolled into WT control group and TCR δ^-/- group. Round full-thickness skin defect with diameter of 6 mm was made on the back of each mouse. The wound healing condition was observed immediately after injury and on post injury day (PID) 2, 4, 6, 8, 10, and the percentage of residual wound area was calculated. (3) Mice were selected to group and reproduce model of full-thickness skin defect as in experiment (2). On PID 3, the tissue of wound margin was collected for hematoxylin eosin staining, and the length of new epithelium was measured. (4) Mice were selected to group and reproduce model of full-thickness skin defect as in experiment (2). On PID 3, epidermal tissue of wound margin was collected to determine expression of proliferating cell nuclear antigen (PCNA) using Western blotting for evaluation of proliferation of epidermal cell. (5) Mice were selected to group and reproduce model of full-thickness skin defect as in experiment (2). On PID 3, epidermal tissue of wound margin was selected and digested into single-cell suspension, and apoptosis of cells was detected by flow cytometer. (6) Forty TCR δ^-/- mice were selected to carry out the same treatment as in experiments (2)-(5). According to the random number table, these mice were enrolled into TCR δ^-/- control group and TCR δ^-/-+ DETC group, with 5 mice in each group for each experiment. Round full-thickness skin defect was made on the back of each mouse. DETC in the number of 1×10⁵ (dissolution in 100 μL phosphate with buffer purity above 90%) were injected through multiple points of wound margin of mice in TCR δ^-/-+ DETC group immediately after injury, and equal volume of phosphate buffer was injected into mice of TCR δ^-/- control group with the same method as above. Data were processed with one-way analysis of variance for repeated measurement, t test, and Bonferroni correction. Results: (1) Along with the culture time elapse, the number of dendritic structures of DETC increased gradually. The percentage of T lymphocytes was 4.67% and 94.1% of these T lymphocytes were DETC. The purity of DETC on CD 15 was 18.50% and the purity of DETC on CD 30 was 98.70%. (2) Immediately after injury, the wound healing condition of mice in WT control group and TCR δ^-/- group was similar. The wound healing speed of mice in TCR δ^-/- group was slower than that in WT control group on PID 2-10. The percentages of residual wound area of mice in TCR δ^-/- group on PID 2, 4, 6, 8, and 10 were increased significantly compared with those in WT control group (t=3.492, 4.425, 4.170, 4.780, 7.318, P<0.01). (3) The length of new epithelium of mice in TCR δ^-/- group on PID 3 was (359 ± 15) μm, which was obviously shorter than that in WT control group [(462±26) μm, t=3.462, P<0.01]. (4) Immediately after injury, wound condition of mice in TCR δ^-/-+ DETC group and TCR δ^-/- control group was similar. Compared with TCR δ^-/-+ DETC group, the wound healing speed of mice in TCR δ^-/- control group were obviously slower on PID 2-10. The percentages of residual wound area of mice in TCR δ^-/-+ DETC group on PID 2, 4, 6, 8, and 10 were decreased significantly compared with those in TCR δ^-/- control group (t=2.308, 3.725, 2.698, 3.707, 6.093, P<0.05 or P<0.01). (5) On PID 3, the length of new epithelium of mice in TCR δ^-/-+ DETC group was (465±31) μm, which was obviously longer than that in TCR δ^-/- control group [(375±21) μm, t=2.390, P<0.05]. (6) On PID 3, PCNA expression of epidermal cell in wound margin of mice in TCR δ^-/- group was 1.25±0.04, which was obviously lower than that in WT control group (2.01±0.09, t=7.415, P<0.01). (7) On PID 3, PCNA expression of epidermal cell in wound margin of mice in TCR δ^-/-+ DETC group was 1.62±0.08, which was significantly higher than that in TCR δ^-/- control group (1.05±0.14, t=3.561, P<0.05). (8) On PID 3, apoptosis rate of epidermal cell in wound margin of mice in TCR δ^-/- group was (16.1±1.4)%, which was higher than that in WT control group [(8.1±0.6)%, t=5.363, P<0.01]. (9) On PID 3, apoptosis rate of epidermal cell in wound margin of mice in TCR δ^-/-+ DETC group was (11.4±1.0)%, which was obviously lower than that in TCR δ^-/- control group [(15.4±1.4)%, t=2.377, P<0.05]. Conclusions DETC participates in the process of wound healing though promoting the proliferation of epidermal cells in wound margin and inhibit the apoptosis of these cells.

Objective:To comprehensively evaluate the correlation between migraine and the risk of hemorrhagic stroke using Meta-analysis.Methods:The published observational studies on migraine and the risk of hemorrhagic stroke in PubMed, EMbase, Cochrane library, Chinese Biomedical Database, China Journal Full-text Database, Wanfang Database and VIP Database were retrieved by computers. The retrieval time limit was from the establishment of the databases to December 31, 2019. Two reviewers independently conducted the literature screening and data extraction, and evaluated the quality according to Newcastle Ottawa scale. Stata SE 12.1 software was used for Meta-analysis.Results:Six case-control studies and 7 cohort studies met the inclusion criteria, all of which were in English. The results of Meta-analysis showed that exposure to migraine increased the risk of hemorrhagic stroke (odds ratio [ OR] 1.47, 95% confidence interval [ CI] 1.23-1.76; P<0.001). Sensitivity analysis showed that the results were robust. Subgroup analysis showed that migraine with aura ( OR 1.38, 95% CI 1.05-1.81; P=0.019), migraine without aura ( OR 1.46, 95% CI 1.19-1.80; P<0.001), male ( OR 2.10, 95% CI 1.72-2.56; P<0.001) and female ( OR 1.53, 95% CI 1.22-1.92; P<0.001) migraine could increase the risk of hemorrhagic stroke. Conclusion:Regardless of the gender of patients and presence or absence of migraine aura, migraine can significantly increase the risk of hemorrhagic stroke.